REVIEW

Li et al., Microbiology 2019;165:1025–1040

DOI 10.1099/mic.0.000818

Virulence mechanisms of plant-pathogenic Streptomyces

species: an updated review
Yuting Li†, Jingyu Liu†, Gustavo Díaz-Cruz†, Zhenlong Cheng and Dawn R. D. Bignell*

Graphical abstract
Potato common scab can be caused by different species of Streptomyces. Although thaxtomin A is the main pathogenicity
factor produced by these pathogens, other phytotoxins, as well as phytohormones and secreted proteins, may play a role in
disease development and/or severity.

Abstract
Gram-positive Actinobacteria from the genus Streptomyces are best known for their morphological complexity and for their
ability to produce numerous bioactive specialized metabolites with useful applications in human and veterinary medicine and
in agriculture. In contrast, the ability to infect living plant tissues and to cause diseases of root and tuber crops such as potato
common scab (CS) is a rare attribute among members of this genus. Research on the virulence mechanisms of plant-patho-
genic Streptomyces spp. has revealed the importance of the thaxtomin phytotoxins as key pathogenicity determinants produced
by several species. In addition, other phytotoxic specialized metabolites may contribute to the development or severity of
disease caused by Streptomyces spp., along with the production of phytohormones and secreted proteins. A thorough under-
standing of the molecular mechanisms of plant pathogenicity will enable the development of better management procedures
for controlling CS and other plant diseases caused by the Streptomyces.

Introduction in soil and aquatic sediments. These organisms are particu-

The genus Streptomyces comprises Gram-positive, filamen- larly renowned for the production of numerous bioactive
tous, spore-forming Actinobacteria that are naturally found specialized metabolites with useful applications in human
000818 © 2019 The Authors

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and veterinary medicine and in agriculture [1]. It is presumed

that in the natural environment of the Streptomyces, the
production of these metabolites serves as a strategy for the
acquisition of nutrients, killing or inhibiting the growth of
competitors, or signalling and intercellular communication
[2–5]. Streptomyces are known to form symbiotic relation-
ships with different eukaryotic organisms, such as plants,
insects and marine animals, and it has been proposed that
the diversity of specialized metabolites produced by the
streptomycetes may have evolved as a direct result of such
interactions (reviewed in [6]). Of particular relevance to
this review is the ability of some Streptomyces species to
establish parasitic interactions with plants, leading to the
development of economically important crop diseases. This
is a rare attribute among the Streptomyces, as only about a
dozen or so species out of the hundreds of species described
are known to function as plant pathogens [7].

Plant-pathogenic Streptomyces spp.

and associated diseases
Most phytopathogenic Streptomyces species cause common
scab (CS) disease, which is an economically important
disease of potato (Solanum tuberosum L.) that occurs
worldwide. The main symptoms associated with the disease
are brown or dark-coloured scab-like lesions on the tuber
surface that can be superficial, erumpent (raised), or deep-
pitted. The type of lesion produced is thought to depend on
factors such as environmental conditions, pathogen load
and aggressiveness, and susceptibility of the potato cultivar
[8]. The lesions often form around lenticels or wound
areas, though neither is a prerequisite for lesion initiation
[9]. They can be small, circular and discrete, or they can Fig. 1. Common scab disease symptoms. (a) A tuber showing a few
coalesce to form large, irregular, corky masses that cover isolated brown lesions. (b) A tuber showing severe scab disease in
significant areas of the tuber surface (Fig. 1). The disease which almost all of the surface is covered with lesions.
reduces the quality and market value of the tuber crop, and
all potato production industries (fresh market, processing,
seed potato) are affected [9]. Potato is the most important CS-causing pathogens are neither tissue- nor host-specific,
host affected by CS disease, though taproot crops such as and in addition to causing disease on root and tuber crops,
beet, radish, carrot and parsnip are also susceptible [10]. they can infect the seedlings of monocot and dicot plants
The disease only affects the underground parts of suscep- in laboratory studies and cause root and shoot stunting,
tible hosts and is restricted to rapidly expanding plant radial swelling and tissue necrosis [12]. The first described
tissues, such as in developing tubers. Once tuber expan- CS-causing pathogen was Streptomyces scabiei (syn.
sion is complete and the mature periderm is formed, lesion S. scabies), which is found in many potato-growing regions
expansion ceases and the tubers are no longer susceptible worldwide [8]. S. scabiei has been isolated from scab lesions
to infection [11]. on a variety of different crops, and it is also associated with

Received 04 April 2019; Accepted 16 May 2019; Published 04 June 2019

Author affiliations: 1Department of Biology, Memorial University of Newfoundland, St John’s, NL A1B 3X9, Canada.
*Correspondence: Dawn R. D. Bignell, ​dbignell@​mun.​ca
Keywords: Streptomyces; common scab; phytotoxins; thaxtomin; secreted proteins; phytohormones.
Abbreviations: AS, Acid Scab; CFA, Coronafacic Acid; CFA-Ile, N-Coronafacoyl-L-Isoleucine; CFA-Val, N-Coronafacoyl-Valine; CK, Cytokinin; COR,
Coronatine; CR, Colonization Region; CS, Common Scab; EFE, Ethylene-Forming Enzyme; ET, Ethylene; GH, Glycohydrolase; IAA, Indole-3-Acetic
Acid; JA, Jasmonic Acid; JA-Ile, Jasmonoyl-L-Isoleucine; mART, mono-ADP-ribosyltransferase; MLP, MbtH-Like Protein; NAD, Nicotinamide Adenine
Dinucleotide; NO, Nitric Oxide; NRPS, Nonribosomal Peptide Synthetase; NS, Netted Scab; PAISa, Streptomyces acidiscabies Pathogenicity Island;
PAISs, Streptomyces scabiei Pathogenicity Island; PAISt, Streptomyces turgidiscabies Pathogenicity Island; PCD, Programmed Cell Death; pv, Pathovar;
SA, Salicylic Acid; Tat, Twin-arginine translocase; TR, Toxicogenic Region.
†These authors contributed equally to this work

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a disease of peanut called peanut pod wart [12]. A closely
related species, Streptomyces europaeiscabiei, has been found
in Europe, North America and Korea. This species causes CS
disease, and some strains can also cause netted scab (NS) of
potato, which is characterized by superficial lesions with a
netted appearance [8]. NS can also be caused by Streptomyces
reticuliscabiei and Streptomyces aureofaciens, and is distin-
guished from CS in that it also produces severe necrosis of
the fibrous roots of potato plants and leads to significant
yield losses [8, 12, 13]. Other species of Streptomyces that are
associated with CS disease include S. turgidiscabies, S. stel-
liscabiei, S. niveiscabiei, S. luridiscabiei and S. puniciscabiei,
and some pathogenic strains of S. bottropensis have also been
reported [8, 14]. A closely related disease called acid scab
(AS) is caused by Streptomyces acidiscabies and is identical
to CS in its symptomology, except that it occurs in low-pH
soils (pH≤5.2) where the growth of S. scabiei and other CS
pathogens is suppressed [12]. Other diseases attributed to
plant-pathogenic Streptomyces spp. include soil rot of sweet
potato [Ipomoea batatas (L.) Lam.] caused by S. ipomoeae,
and potato russet scab caused by different Streptomyces strains
[12, 15, 16].
Virulence mechanisms of plant-
pathogenic Streptomyces spp
Research on plant-pathogenic Streptomyces spp. over the last
several years has provided vital clues for understanding how
these organisms are able to colonize and infect a living plant
host and cause disease. Such work has been greatly assisted by
the availability of an increasing number of genome sequences
from both pathogenic and nonpathogenic streptomycetes.
The first pathogen genome sequence was completed in 2005
and was of S. scabiei 87–22 (DDBJ/EMBL/GenBank accession
number NC_013929), a strain originally isolated in the USA
from a deep-pitted lesion on the scab-resistant potato cultivar
Russet Burbank [17]. Since then, the genome sequences of
other strains of S. scabiei, as well as other pathogenic species,
have been completed [9, 18–21], providing an opportunity for
comparative genomic analyses in order to identify novel viru-
lence factors in these organisms. In this review, we provide an
overview of our current knowledge of the known virulence
factors contributing to host infection and disease develop-
ment by pathogenic Streptomyces spp., as well as other factors
that are potentially involved in mediating Streptomyces–plant
interactions. For simplicity’s sake, we have organized the
known or potential virulence factors into the following three
main categories – phytotoxins, phytohormones and secreted
proteins.
Phytotoxins
Early research into the mechanisms of plant pathogenicity
in Streptomyces revealed the role of phytotoxic specialized
metabolites (phytotoxins) as key pathogenicity factors
in these organisms. The first phytotoxins associated with
Streptomyces plant pathogenicity were thaxtomin A and B,
which were isolated from S. scabiei-infected tuber tissue [22].
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Although thaxtomins are now considered to be the principal
pathogenicity determinant associated with diseases such as
CS and AS, there is now evidence that other phytotoxins may
play a key role in the development or severity of plant diseases
caused by Streptomyces spp., including CS [7].
Thaxtomins
General features
Thaxtomins are a family of phytotoxic specialized metabo-
lites that consist of cyclic dipeptides (2,5-diketopiperazines)
derived from l-phenylalanine and L-4-nitrotryptophan
[7, 23]. Eleven thaxtomin analogues have been identified,
and they vary in the incorporation of hydroxyl and N-methyl
groups at specific locations on the thaxtomin backbone
[23]. Thaxtomin A (Fig. 2) is the major thaxtomin analogue
produced by S. scabiei, although other analogues have been
detected in low amounts in plant materials infected with this
pathogen [23]. S. turgidiscabies, S. acidiscabies and S. euro-
paeiscabiei also produce thaxtomin A as the major product,
and at least four other pathogenic species or strains (S. stel-
liscabiei, S. niveiscabiei, Streptomyces sp. IdahoX, Streptomyces
sp. DS3024) can produce thaxtomin [7, 23]. A less-modified
thaxtomin analogue, thaxtomin C (Fig. 2), is the major
product that is produced by S. ipomoeae [24, 25].
Biological activities
Several studies have shown a positive correlation between
the production of thaxtomin and the pathogenicity of
Streptomyces spp. [17, 25–29]. Pure thaxtomin A can induce
necrosis on excised potato tuber tissue [11], and cell-free
extracts containing thaxtomin A and B can induce scab-like
lesions on aseptically cultured minitubers [30]. In addition,
treatment of monocot and dicot seedlings with thaxtomin A
results in seedling stunting, hypocotyl and root swelling, cell
hypertrophy and tissue necrosis, effects that mimic the seed-
ling pathogenicity phenotype of S. scabiei and S. acidiscabies
[12, 31]. Several lines of evidence suggest that thaxtomin A
functions as a cellulose biosynthetic inhibitor, although the
specific cellular target of the toxin remains unknown [32–35].
Thaxtomin A also activates the expression of defence-related
genes and induces programmed cell death (PCD) in Arabi-
dopsis, and it stimulates the production of the antimicrobial
plant defence compound scopoletin in both Arabidopsis
and tobacco (Nicotiana tabacum) [34–38]. In addition, it
induces a rapid Ca2+ influx across the plasma membrane,
which is typical of an early plant defence response and is a
prerequisite for the induction of PCD [39, 40]. In a recent
study, a mutant of Arabidopsis with enhanced sensitivity to
thaxtomin A was found to exhibit more severe alterations
in Ca2+ and K+ fluxes in response to thaxtomin A treatment
as compared to the wild-type control, suggesting a distur-
bance in the regulation of ion movement across the plant
cell membrane [41]. Notably, the Arabidopsis mutant also
showed enhanced sensitivity to the cellulose biosynthesis
inhibitor isoxaben, suggesting that isoxaben and thaxtomin
may share a common mode of action, a notion supported by
other studies [35, 42].
 Li et al., Microbiology 2019;165:1025–1040

Fig. 2. Chemical structures of different phytotoxins produced by plant-pathogenic Streptomyces spp. Shown are thaxtomin A and C
(i), N-coronafacoyl-l-isoleucine (ii), borrelidin (iii), concanamycin A and B (iv), desmethylmensacarcin (v), fridamycin E (vi) and FD-891
(vii).

Thaxtomin biosynthesis the nitrotryptophyl and phenylalanyl moieties, and it is likely

The production of the thaxtomin family of molecules is
exclusive to plant-pathogenic Streptomyces spp. and involves
a biosynthetic gene cluster that is highly conserved in these
species [18]. In scab-causing Streptomyces spp., the cluster
consists of seven genes, of which six (txtA, txtB, txtC, txtD,
txtE and txtH) encode proteins involved in metabolite biosyn-
thesis, and one (txtR) encodes a cluster-situated regulator of
phytotoxin production [7, 18, 43]. The biosynthesis of thax-
tomin commences with the production of nitric oxide (NO)
from l-arginine by the nitric oxide synthase TxtD [44]. A
unique cytochrome 450 monooxygenase, TxtE, then nitrates
l-tryptophan using the NO produced by TxtD, generating
the intermediate L-4-nitrotryptophan [45]. Two nonribo-
somal peptide synthetases (NRPSs), TxtA and TxtB, utilize
l-phenylalanine and L-4-nitrotryptophan as substrates,
respectively, to generate a cyclic dipeptide intermediate called
thaxtomin D [46–48]. Thaxtomin D is N-methylated on both
that the methylation steps are catalyzed by the S-adenosylme-
thionine-dependent N-methyltransferase domains found in
TxtA and TxtB [7]. Hydroxylation of the phenylalanyl moiety
by the TxtC cytochrome P450 monooxygenase is the final step
in the synthesis of thaxtomin A [48]. The thaxtomin biosyn-
thetic gene cluster in S. ipomoeae lacks a txtC homologue, and
this agrees with the observation that this organism does not
produce thaxtomin A [18, 24].
Recent research from our laboratory has provided insights
into the role of the txtH gene that is located immediately
downstream of txtB in the thaxtomin gene cluster [7, 43].
txtH encodes a member of the MbtH-like protein (MLP)
family, which are typically required for the proper function of
NRPS enzymes [49]. Deletion of txtH resulted in a significant
reduction in thaxtomin A production in S. scabiei, although
some production could still occur (Y. Li, unpublished). It

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was predicted that two other MLPs encoded in the S. scabiei
genome might be able to partially compensate for the loss
of TxtH, since MLPs from different biosynthetic pathways
are known to exhibit functional crosstalk [50–53], and this
was confirmed by the construction of an MLP triple mutant,
for which thaxtomin A production was completely abolished
(Y. Li, unpublished). As txtH is conserved in the thaxtomin
gene clusters of plant-pathogenic Streptomyces spp. [7, 43],
our results suggest that TxtH is a key component of the thax-
tomin biosynthetic machinery in these species.
Regulation of thaxtomin production
The txtR gene within the thaxtomin gene cluster of plant-
pathogenic Streptomyces spp. encodes an AraC/XylS family
transcriptional regulator [7, 43, 54]. Disruption of this gene
in S. scabiei causes a reduction in the expression of txtA, txtB,
txtC and txtD and eliminates thaxtomin A production, and
the virulence of the mutant is severely reduced as compared
to wild-type S. scabiei [54]. Cellobiose, the smallest unit of
cellulose and a known inducer of thaxtomin A production,
can serve as a ligand for the S. scabiei TxtR and can induce
the expression of txtR and the thaxtomin biosynthetic genes
[54, 55]. The exposure of rapidly growing tobacco cell suspen-
sions to thaxtomin A causes the release of cellotriose, which
also serves as an inducer of thaxtomin production. Based
on these results, it was proposed that scab-causing Strepto-
myces spp. upregulate thaxtomin production and virulence
in response to cello-oligosaccharides that are released from
thaxtomin-sensitive plant tissues [55].
Given that thaxtomin A targets cellulose biosynthesis in
plants, it was hypothesized that cello-oligosaccharides may
act as environmental signals for the perception of actively
expanding plant tissues that serve as infection sites for scab-
causing pathogens [56]. Indeed, recent studies have shown
that the expression of txtR in S. scabiei is controlled by CebR,
which has been characterized as a repressor of cellulose/
cellobiose/cello-oligosaccharide utilization in nonpathogenic
streptomycetes [57]. CebR binds to two sites (cbs) within the
thaxtomin gene cluster – one located upstream of txtR, and
another located within the txtB gene (Fig. 3). Cellobiose and
cellotriose serve as ligands for CebR and inhibit the DNA-
binding activity of the repressor, thereby inducing expres-
sion of the thaxtomin biosynthetic and regulatory genes [57].
Notably, deletion of cebR results in constitutive thaxtomin
A production and a hypervirulence phenotype, suggesting
that CebR serves as the ‘gatekeeper’ of pathogenicity in
S. scabiei [57]. A subsequent study revealed that the transport
of cellobiose and cellotriose into the cell by the CebEFG-MsiK
ABC transporter system is required for the cello-oligosac-
charide-mediated induction of thaxtomin production in
S. scabiei [58].
Given that cello-oligosaccharides can be produced through
the enzymatic degradation of cellulose from dead plant mate-
rial, it is unclear how S. scabiei and other scab-causing patho-
gens can sense the source of the cello-oligosaccharides that
induce thaxtomin production and pathogenicity. Expanding
plant tissues serve as both the site of action of thaxtomin and
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the infection site of the pathogen, and thus a mechanism
must be in place to prevent the unnecessary production of
the phytotoxin in the absence of expanding plant tissues
[59]. One possibility lies in the observation that cellotriose
is a more effective inducer of thaxtomin production than
cellobiose, and that cellotriose but not cellobiose is released
from actively growing plant tissues [55]. This has led to the
proposal that cellotriose may serve as a specific signal for the
presence of expanding plant tissues, while cellobiose, which is
the main product of cellulose degradation by the cellulolytic
system, may serve as a signal for the presence of dead cell
material [59]. This idea is supported by the observation that
the CebE component of the cello-oligosaccharide transporter
binds cellotriose with a much higher affinity than cellobiose,
suggesting that S. scabiei has the ability to sense and respond
to very low levels of cellotriose released from expanding plant
tissues [58].
An additional inducer of thaxtomin production in S. scabiei
is suberin, an insoluble lipidic biopolymer that is one of
the main components of the potato periderm [60]. A study
by Lerat et al. showed that S. scabiei cultured in a minimal
medium containing cellobiose or suberin produced only
trace levels of thaxtomin A, whereas the addition of
both cellobiose and suberin to the medium significantly
enhanced the phytotoxin production level, as well as
expression of the thaxtomin biosynthetic genes [61]. This
suggests that suberin and cellobiose exhibit a synergistic
effect on thaxtomin production in S. scabiei. While it is
unclear how suberin functions as an inducer of thaxtomin
biosynthesis, a proteomic analysis revealed that suberin
upregulates proteins related to morphological differentia-
tion and secondary metabolism in S. scabiei [62], and it has
been shown to hasten morphological differentiation and to
enhance the production of secondary metabolites in both
pathogenic and nonpathogenic Streptomyces spp. [63].
Notably, Padilla-Reynaud and colleagues recently found
that suberin stimulates the production of glycosyl hydro-
lases such as cellulases when added to media containing
cellulose [64]. This led to the proposal that the onset of
virulence mechanisms in S. scabiei requires both suberin
and cellulose, where the former stimulates the production
of cellulases that generate cellobiose from the cellulose.
Thaxtomin production, in turn, is induced both by the
cellobiose generated and by suberin, which serves as a
general trigger of specialized metabolism in Streptomyces
spp. [64].
The production of thaxtomin in S. scabiei is additionally
under the control of several members of the bld (bald)
gene family of global regulators that control morphological
development, and in some cases secondary metabolism in
Streptomyces spp. [65]. The txtR cluster-situated regulatory
gene contains a single TTA codon, the translation of which
requires the leucyl-tRNA encoded by the bldA gene. Dele-
tion of bldA in S. scabiei abolishes thaxtomin A produc-
tion and significantly reduces expression of the thaxtomin
biosynthetic genes [66]. Other bld genes that were shown
to modulate thaxtomin biosynthetic gene expression and
 Li et al., Microbiology 2019;165:1025–1040

Fig. 3. Model of thaxtomin A regulation in S. scabiei. Cello-oligosaccharides are predicted to be released from expanding cell walls and
are transported into the S. scabiei through the CebEFG-MsiK ABC transporter. Once inside the cell, the cello-oligosaccharides bind to
CebR, and this results in the derepression of the thaxtomin gene cluster by causing the release of CebR from the cbs sites (indicated
by ○). Expression of the thaxtomin biosynthetic genes, which may be enhanced by the binding of cellobiose to the TxtR activator, leads
to the production of thaxtomin A, which then inhibits cellulose biosynthesis in expanding plant tissues and causes the release of
more cellotriose, thereby creating a positive feedback loop for thaxtomin A biosynthesis. The main component of the potato periderm,
suberin, is also known to stimulate thaxtomin A production, presumably by affecting secondary metabolism in S. scabiei. In addition, the
expression of txtR is regulated by the bldA tRNA, which is required for translation of the TTA codon within the txtR coding sequence, as
well as by the transcriptional regulators bldC, bldD, bldG and bldH. Image made in BioRender (biorender.com).

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Fig. 4. Schematic diagram showing the genetic organization of the pathogenicity islands from Streptomyces turgidiscabies Car8,
Streptomyces scabiei 87–22 and Streptomyces acidiscabies 84.104. The complete S. turgidiscabies pathogenicity island (PAISt, 674 kb)
is flanked by two attachment sites (attL and attR) consisting of an 8 bp palindromic sequence. The PAISt can be further divided into
two modules that are separated by an internal attachment site (attI). The 569 kb module contains the thaxtomin (txt) gene cluster
(green arrow), the plant fasciation (fas) gene cluster (red arrow) and an integrase (intSt) gene (grey arrow), while the 105 kb module
contains nec1 (blue arrow), tomA (yellow arrow) and a remnant of the intSt gene (grey triangle). attR is located within the 3′ end of the
bacA gene (purple arrow), while attL and attI are located within truncated copies of the bacA 3′ end (purple triangles). The S. scabiei and
S. acidiscabies pathogenicity islands (PAISs and PAISa) consist of two distinct regions designated the colonization region (CR) and the
toxicogenic region (TR). The CR in both species is identical to the 105 kb module from the PAISt, except that it is flanked by imperfect 8 bp
palindromic att sites (residues that are different are in red). The TR region in S. scabiei is flanked by 12 bp attL and attR sites and contains
an internal attI site that divides the region into two sub-regions called TR1 and TR2. TR1 is conserved in S. acidiscabies and contains the
txt gene cluster, while TR2 is missing from S. acidiscabies and contains an integrase gene (black arrow), a recombination directionality
factor gene (white arrow) and conjugation genes (light blue arrow). The complete TR in S. scabiei and the TR1 in S. acidiscabies is inserted
at the 3′ end of the aviXI gene (brown arrow). The fas gene cluster is missing from both S. scabiei and S. acidiscabies. Note that other
genes present on the PAIs are not shown here. Diagram is not to scale.

metabolite production include bldC, bldD, bldG and bldH,
all of which encode transcriptional regulators [66].
Horizontal gene transfer of the thaxtomin biosynthetic genes
The conservation of the thaxtomin biosynthetic gene cluster
among phylogenetically distinct Streptomyces spp. suggests
that horizontal gene transfer has played a role in the emer-
gence of new plant-pathogenic Streptomyces species in
agricultural settings [11, 18]. In S. turgidiscabies Car8, the
thaxtomin biosynthetic genes, along with other known or
putative virulence factors, are localized on a large (674 kb)
pathogenicity island (PAISt) that can transfer to other Strep-
tomyces species and integrates by site-specific recombination
at an 8 bp palindromic sequence (TTCATGAA) within the
3′ end of the bacitracin resistance gene bacA (Fig. 4) [67, 68].
The PAISt excises from the S. turgidiscabies chromosome in
modules of different sizes, and transfer of the complete PAISt
can confer a pathogenic phenotype on the nonpathogenic
species Streptomyces diastatochromogenes [67, 68]. In S. scabiei
87–22 and S. acidiscabies 84.104, the virulence genes found on
the PAISt are localized in two separate regions of the chromo-
some, called the toxicogenic region (TR) and the colonization
region (CR) (Fig. 4). The thaxtomin biosynthetic genes are
located in the TR, while other known or putative virulence
genes such as nec1 and tomA are found in the CR [43, 68, 69].
The S. scabiei TR can be further divided into two sub-regions
(TR1 and TR2) that are flanked by two attachment (att) sites
and are separated by an internal att site. TR1, which is 20 kb
in size, contains the entire thaxtomin gene cluster, and TR2,
which is 157 kb, includes putative integrative and conjugative
elements (Fig. 4) [70]. Zhang and colleagues showed that the
CR and TR1 are conserved in several different pathogenic
Streptomyces species, while TR2 is only conserved in strains
of S. scabiei and a novel pathogenic strain (96–12) from Egypt
[43]. The entire TR in S. scabiei and in Streptomyces sp. 96–12,
as well as the TR1 in S. acidiscabies and S. europaeiscabiei, is
integrated at the 3′ end of an aviXI gene encoding a putative

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ATP/GTP-binding protein (Fig. 4) [43, 70]. Excision of the
entire TR, as well as TR1 and TR2, from the S. scabiei 87–22
chromosome has been detected, but only TR2 or the entire
TR could be transferred into the genome of a nonpathogenic
recipient, and the recipient only became pathogenic after
receiving the entire TR [43, 70]. These results suggest that
TR2 is required for mobilization, while TR1 is required for
pathogenicity, and both are required for the emergence of new
plant-pathogenic species [43]. It is notable, however, that the
genetic background of strains acquiring the thaxtomin gene
cluster on the TR and PAISt influences the ability of the recipi-
ents to produce thaxtomin A [67, 71]. This may explain why
the emergence of new plant pathogens is relatively infrequent
in agricultural systems [11].
Coronafacoyl phytotoxins
The ability of S. scabiei to produce coronafacoyl phyto-
toxins was first established when a biosynthetic gene cluster
predicted to produce such metabolites was identified in the
genome sequence of S. scabiei 87–22 [72]. Several features
of coronafacoyl phytotoxin production in S. scabiei and in
other plant pathogens were already covered in detail in a
recent review from our laboratory [73]. Here, we will limit
our discussion to the general features of this family of phyto-
toxins, their bioactivities and proposed roles in pathogen
infection and disease development.
General features
Coronafacoyl phytotoxins are non-host-specific phytotoxins
that are known or suspected to be produced by different
plant-pathogenic bacteria, including several pathovars (pv)
of Pseudomonas syringae [73]. Members of this phytotoxin
family are composed of the bicyclic hydrindane ring-based
polyketide coronafacic acid (CFA) and an amino acid or
amino acid derivative linked via an amide bond. Coronatine
(COR), the best-characterized coronafacoyl phytotoxin, is
the primary family member produced by P. syringae and
other Pseudomonas spp. and consists of CFA linked to an
ethylcyclopropyl amino acid called coronamic acid [73].
Recently, S. scabiei 87–22 was shown to be able to produce
N-coronafacoyl-l-isoleucine (CFA-Ile) (Fig. 2), which is also
produced by P. syringae in minor amounts [74]. Other minor
coronafacoyl phytotoxins have also been reported in S. scabiei
and/or Pseudomonas spp., including CFA-allo-isoleucine,
CFA-serine, CFA-valine (CFA-Val), CFA-norvaline, CFA-
threonine and norcoronatine [73].
Biological activities
Most studies on the bioactivity of coronafacoyl phytotoxins
have focused on COR, since it is the predominant family
member produced by P. syringae and is the most toxic form
[73]. COR exhibits a wide range of biological activities in
plant tissues, including induction of tissue hypertrophy
and diffuse leaf chlorosis, stimulation of ethylene produc-
tion, anthocyanin accumulation, inhibition of root elonga-
tion, changes in chloroplast structure and accumulation of
proteinase inhibitors. CFA-Ile and other family members,
such as CFA-Val, display similar bioactivities to COR, but
1032
are not as biologically active as COR. In contrast, CFA alone
exhibits very little to no biological activity, indicating that
the attached amino acid is essential for the toxic effects of
coronafacoyl phytotoxins [73].
Proposed role in pathogen infection and disease
development
Coronafacoyl phytotoxins are important virulence factors
that contribute to pathogen persistence and disease symptom
development, although they are not essential for pathogenicity
of the producing organism [73]. COR has been shown to
function by activating jasmonic acid (JA) signalling in plants
due to its ability to interact with the same host receptor as
jasmonoyl-l-isoleucine (JA-Ile), the most bioactive form of
JA (Fig. 5) [75, 76]. JA is an important signalling molecule
that controls various biological processes, including defence
against herbivores and necrotrophic pathogens [77]. Another
important signalling pathway in plants is the salicylic acid
(SA) pathway, which is responsible for regulating defence
again biotrophic and hemibiotrophic pathogens, among other
things [77]. The JA and SA signalling pathways are antago-
nistic in that activation of JA signalling leads to inhibition of
SA signalling pathways, and vice versa [78]. Thus, activation
of the JA signalling pathway by COR leads to suppression of
SA-mediated signalling, which is critical for host defences
against infection by P. syringae [79]. COR also suppresses
callose deposition in an SA-independent manner, and it
facilitates pathogen entry into the plant host by overcoming
stomatal defences [80, 81]. Therefore, the production of COR by
P. syringae provides an adaptive advantage by allowing the
pathogen to manipulate the hormone signalling networks to
overcome host defences during infection [82].
The role of coronafacoyl phytotoxin production in CS
disease development remains unclear, but as S. scabiei
is the only plant-pathogenic Streptomyces sp. known to
produce this family of phytotoxins [73], the phytotoxins
are not essential pathogenicity determinants for the
induction of CS disease. Recent work from our labora-
tory, however, suggests that there is a positive correlation
between CFA-Ile production levels and the severity of
disease symptom development on potato tuber tissue [84].
Previously, a mutant strain of S. scabiei 87–22 that could
not produce CFA-Ile was shown to exhibit the same viru-
lence phenotype as the wild-type strain in a potato tuber
bioassay [72], but work from our laboratory has shown that
S. scabiei 87–22 only produces trace levels of CFA-Ile in
liquid culture [74]. Thus, to examine the impact of CFA-Ile
production on the virulence of S. scabiei, we constructed
strains that produced elevated levels of CFA-Ile, and we
showed that higher phytotoxin production levels corre-
lated with increased necrosis and pitting of the potato
tuber tissue (Fig. 6) [84]. Our results therefore suggest that
the severity of CS disease symptoms caused by different
S. scabiei strains may be mediated in part by the relative
levels of coronafacoyl phytotoxins produced by each strain.
It remains to be determined whether CFA-Ile produc-
tion contributes to host invasion or suppression of plant
 Li et al., Microbiology 2019;165:1025–1040

Fig. 5. Role of coronafacoyl phytotoxins in modulating jasmonate hormone signalling in plants. COR produced by P. syringae is structurally
similar to JA-Ile and functions as a molecular mimic of JA-Ile by interacting with the same host receptor. JA-Ile and COR both promote the
interaction of the SCFCOI1 ubiquitin ligase with JAZ transcriptional repressors, and this leads to ubiquitination and subsequent destruction
of the JAZ repressor proteins by the 26S proteasome. JAZ protein degradation allows transcription factors (TF) (e.g. MYC2) associated
with the promoters of early JA-responsive genes to activate target gene expression. CFA-Ile produced by S. scabiei is structurally similar
to both COR and JA-Ile, and thus it is predicted to activate jasmonate signalling pathways in a similar manner. Note that other proteins
involved in repression or activation of JA-responsive genes in plants [83] are not shown here. Image made in BioRender (biorender.com).

defence responses in the same way as COR; however, the
structural similarities between COR, CFA-Ile and JA-Ile
suggest that CFA-Ile might also function as a JA-Ile mimic
and induce JA signalling pathways during pathogen infec-
tion (Fig. 5). Interestingly, a recent analysis of the National
Center for Biotechnology Information (NCBI) database
revealed that coronafacoyl phytotoxin biosynthetic genes
are not confined to plant-pathogenic bacteria species, but
can also be found in nonpathogenic bacteria, including
several Streptomyces spp. [73]. This suggests that corona-
facoyl phytotoxins are not exclusively virulence factors and
that there are likely additional roles for these metabolites
that remain to be discovered.
Concanamycins
Concanamycins were first isolated from S. diastatochromo-
genes S-45 [85] and are characterized by an 18-membered
tetraenic macrolide ring incorporating a methyl enol ether,
and by a β-hydroxyhemiacetal side chain. Concanamycins
display antifungal and anti-neoplastic activity, but not
antibacterial activity [7]. Strains of S. scabiei isolated in

1033
 Li et al., Microbiology 2019;165:1025–1040
Fig. 6. Increased CFA-Ile production by S. scabiei is correlated with
enhanced disease symptom severity on potato tuber tissue. Tuber
discs were infected with wild-type S. scabiei 87–22 (i) and with two
engineered S. scabiei strains (ii, iii) that produce elevated levels of CFA-
Ile. A vector control strain (iv) was also included. The relative level of
CFA-Ile produced by each strain is as follows: i ≈ iv<ii<iii.
Japan were shown to produce two members of the concana-
mycin family – concanamycin A and B (Fig. 2) – and both
compounds were shown to exhibit root growth inhibitory
activity against rice (Oryza sativa), rape (Brassica napus)
and alfalfa (Medicago sativa) seedlings [16, 86]. A biosyn-
thetic gene cluster for concanamycin was identified in the
genome sequence of S. scabiei 87–22 [87], and production
of concanamycin A by this strain was confirmed in oat
bran broth [88]. As with CFA-Ile, other plant-pathogenic
Streptomyces spp. do not appear to produce concanamycins
[16, 89, 90].
Recently, Natsume and colleagues examined the effects of
concanamycins on the lesion type formed during infection
of potato tubers by plant-pathogenic Streptomyces spp. [91].
The authors showed that treatment of potato tuber slices with
pure concanamycin A produces slightly sunken lesions, while
thaxtomin A treatment results in a flat, necrotic surface. In
addition, a synergistic effect was observed when both phyto-
toxins were added to the same tuber slice [91]. Concanamycin
A and B were detected in lesions of pot-grown potato tubers
infected with S. scabiei but not with S. acidiscabies. Notably,
the potatoes infected with S. scabiei had deep-pitted lesions,
while the S. acidiscabies-infected potatoes had corky, raised
lesions. A similar observation was made with field-grown
diseased potatoes, where the concanamycin content tended
to be higher in tubers with deep-pitted lesions than in those
with corky, raised lesions. Overall, the results suggest that
differences in concanamycin production by Streptomyces spp.
may contribute to the observed differences in lesion types on
scab-infected potato tubers [91].
Other phytotoxins
Recent studies have revealed that other phytotoxic special-
ized metabolites might play a role in disease development
by Streptomyces spp. isolated from specific regions. In Iran,
1034
for example, a Streptomyces strain was isolated from deep-
pitted lesions on potato tubers and was shown to produce
the 18-membered macrolide borrelidin (Fig. 2). Bioassays
revealed that the pure borrelidin could induce necrosis of
potato tuber tissue and cause stunting of radish (Raphanus
sativa) seedlings [92]. The polyketide desmethylmensac-
arcin (Fig. 2) was purified from cultures of a S. niveiscabiei
strain isolated in Uruguay, and the pure compound was
shown to induce deep necrotic lesions on potato tuber tissue
and to cause stunting of radish seedlings, and it was more
aggressive than pure thaxtomin A in the bioassays [93].
Fridamycin E (Fig. 2) was recently purified from cultures of a
S. turgidiscabies strain that was isolated from NS lesions on
potato tubers in northern Sweden, and the compound was
able to inhibit the sprouting of potato microtubers or reduce
the growth of sprouts in a concentration-dependent manner,
although it did not induce NS lesions on the microtubers [94].
A new species of Streptomyces called S. cheloniumii, which
is closely related to S. diastatochromogenes, was isolated in
Japan and was found to cause russet-like scab symptoms, but
not CS symptoms, on potato tubers [16]. A 16-membered
macrolide called FD-891 (Kamenoko-byo toxin) (Fig. 2) was
isolated from culture extracts of the organism and was able to
cause necrosis of potato tuber tissue and inhibit root growth
in rice and shoot growth in alfalfa [16]. In a recent study
from our laboratory, a Streptomyces strain was isolated from
a CS lesion on a potato tuber in Newfoundland, Canada, and
this strain was shown to produce a compound that exhibits
phytotoxicity against different plant species, although this
compound has not yet been identified [88]. It is noteworthy
that in all of the cases described, thaxtomin phytotoxins were
not produced by any of the pathogenic strains, and this was
confirmed in several instances by genome sequencing of the
strains or by microarray or Southern analysis using probes
specific for the thaxtomin cluster [21, 92–94]. In addition,
the identified compounds were not previously known to
exhibit phytotoxicity. It remains to be determined whether
these phytotoxins are essential pathogenicity determinants
for the producing organisms, but the absence of thaxtomin
production in these strains suggests that multiple phytotoxic
specialized metabolites contribute to the pathogenic pheno-
type of Streptomyces spp.
Phytohormones
Plant pathogens have evolved strategies to influence plant
hormone signalling pathways in order to facilitate infection
of the host. For example, some pathogens produce toxins
or effectors that manipulate phytohormone signalling path-
ways and, as discussed already, the production of COR by P.
syringae is an example of such a strategy. In addition, many
plant pathogens produce phytohormones such as cytokinins,
auxin and ethylene as a way to alter hormone signalling in the
host. As hormones regulate various processes during growth
and stress responses in plants, the manipulation of phytohor-
mone signalling pathways can allow pathogens to suppress
plant defence responses and/or take over development and
nutrient allocation processes in order to facilitate colonization
 Li et al., Microbiology 2019;165:1025–1040
and dissemination. We direct readers to a recent review for
more information on this topic [95]. Here, we will focus
on the production of phytohormones by plant-pathogenic
Streptomyces spp. and their potential role in the virulence of
these organisms.
Cytokinins
Cytokinins (CKs) are classically known as ‘growth’ hormones
due to their role in regulating plant growth and development.
Many plant pathogens produce CKs to assist the translocation
of nutrients into infection sites in order to enhance pathogen
proliferation [95]. In a study by Kers and colleagues, a putative
CK biosynthetic gene cluster was identified adjacent to the
thaxtomin gene cluster on the S. turgidiscabies PAISt (Fig. 4)
[67]. The gene cluster was determined to be highly similar in
content and organization to the plant fasciation (fas) operon
that is present in Rhodococcus fascians, which induces leafy
galls on a wide range of plant hosts [67, 96]. The R. fascians
fas genes are located on a linear virulence plasmid [97], while
in S. turgidiscabies the fas operon is flanked by two trans-
posable elements on the chromosome [98]. Intriguingly, the
fas operon is not present in other scab-causing Streptomyces
spp. (Fig. 4), suggesting that the operon was obtained by
S. turgidiscabies Car8 after the PAISt was mobilized into this
organism [43, 67, 98].
The R. fascians fas operon is required for the pathogenicity
of the organism [99] and directs the synthesis of a mixture of
CKs [100]. In S. turgidiscabies, the genes within the fas operon
are all expressed under conditions that support thaxtomin
production, and culture supernatants were shown to exhibit
CK activity [98]. Furthermore, Arabidopsis and tobacco
seedlings infected with a thaxtomin-deficient mutant of
S. turgidiscabies developed leafy galls, and this effect was
not observed when a fas operon mutant was used in infec-
tion assays [98]. It is unclear what role CK production by
S. turgidiscabies plays in pathogen infection and CS disease
development, but it is noteworthy that this species has been
reported to produce particularly large, erumpent lesions on
potato tubers, and it is possible that CK production contrib-
utes to greater reproduction or dispersal of the pathogen in
these larger lesions [98].
Indole-3-acetic acid
Indole-3-acetic acid (IAA) is the best-characterized member
of the auxin class of plant hormones and plays a critical role
in regulating plant growth and development [95]. IAA can be
produced by a wide variety of plant growth-promoting and
plant-pathogenic bacteria, and the biosynthesis of IAA involves
three major pathways that use l-tryptophan as the starting
precursor [101]. Studies have shown that IAA is a relevant
virulence factor in several plant-pathogenic bacteria [87, 102].
In the genus Streptomyces, production of IAA has been found
across several species, including S. scabiei [87]. The genome of
S. scabiei 87–22 revealed the presence of the genes scab_75511
and scab_75501, which are homologues of iaaM and iaaH,
respectively of the indole-3-acetimide pathway, which is
the best-characterized pathway in phytopathogenic bacteria
1035
[87, 101]. Mutants of S. scabiei lacking either iaaH or iaaM
had reduced IAA production and caused less necrosis on
radish roots compared to the wild-type strain [103]. However,
a study by Lerat and colleagues showed that the production
of IAA by S. scabiei is significantly enhanced by the addition
of l-tryptophan to the culture medium, while thaxtomin A
production was reduced under the same conditions, as was
virulence on radish seedlings [104]. Thus, the role of IAA
production as a virulence factor for S. scabiei requires further
investigation.
Ethylene
Ethylene (ET) is a volatile hormone that, together with JA,
is an important regulator of plant defence responses against
necrotrophic pathogens [105]. In S. scabiei 87–22, a homo-
logue of the microbial ethylene-forming enzyme (EFE) was
predicted to be encoded in the genome of this organism [87].
EFE is classified as a member of the Fe(II)- and 2-oxoglu-
tarate-dependent oxygenase superfamily and catalyzes the
synthesis of ET from 2-oxoglutarate [106]. ET production
by plant-pathogenic microbes such as P. syringae, Ralstonia
solanacearum and Botrytis cinerea has been documented
[95], and although disruption of the efe gene in P. syringae pv.
phaseolicola did not affect virulence, efe mutants of P. syringae
pv. glycinea were significantly reduced in their ability to grow
in planta [107]. Currently, it is unknown whether S. scabiei
produces ET and whether ET contributes to the virulence
phenotype of this organism.
Secreted proteins
In addition to producing small molecules, many plant-path-
ogenic microbes secrete proteins, typically called effectors,
into host plant cells in order to promote pathogenesis, or they
produce extracellular enzymes that break down plant cell wall
polymers for nutrient acquisition and to enable penetration
and spread through host tissues [108, 109]. The following is an
overview of some of the secreted proteins that are known or
suspected to be involved in the pathogenicity of Streptomyces
spp.
Nec1
The nec1 gene was initially discovered in a genetic screen
meant to identify the thaxtomin biosynthetic genes [11].
nec1 encodes a 16 kDa secreted protein that exhibits necro-
genic activity on excised potato tissue [110]. The low G+C
content (54%) of the gene relative to the rest of the Strep-
tomyces genome, together with the presence of flanking
sequences similar to transposon elements, suggests that the
gene was transferred into Streptomyces spp. from a different
source, although to date no known homologues have been
identified in the DNA or protein databases [110]. nec1 is
conserved in several scab-causing species and is located on
the PAISt in S. turgidiscabies and in the CR in S. scabiei,
S. acidiscabies, S. europaeiscabiei and S. stelliscabiei (Fig. 4)
[43, 67, 69]. However, nec1 is not an essential pathogenicity
factor, as several pathogenic Streptomyces strains lack this
gene [14, 111–113].
 Li et al., Microbiology 2019;165:1025–1040
The Nec1 protein may be secreted by Streptomyces spp.
using either the Sec or Tat secretion pathways based on
bioinformatics analysis of the N-terminal amino acid
sequence [114]. Although the protein lacks any recogniz-
able domains or motifs, the C-terminal region is essential
for its necrotizing activity. Deletion of nec1 in S. turgidis-
cabies greatly reduces its virulence in plant bioassays using
Arabidopsis, tobacco and radish as hosts, and the mutant is
compromised in its ability to aggressively colonize radish
roots [114]. Currently, the specific target of Nec1 and its
function remain unknown, although it has been suggested
that Nec1 functions early in the infection process and may
be involved in the suppression of plant defence responses
[114].
Very little is known regarding the regulation of nec1 expres-
sion in pathogenic Streptomyces spp., although it has been
determined that the protein is produced and secreted in a rich
medium that does not support thaxtomin production [114].
The expression of the nec1 gene is also not dependent on the
thaxtomin inducer, cellobiose [55]; however, expression does
appear to be modulated by several bld gene global regulators
that also control thaxtomin production in S. scabiei [66].
TomA
The tomA gene was first discovered in a partial sequence of
the PAISt from S. turgidscabies Car8 [67]. Like nec1, the gene
is conserved in several scab-causing streptomycetes and is
located in the CR in S. scabiei, S. acidiscabies, S. europaeiscabiei
and S. stelliscabiei (Fig. 4) [43, 67, 69]. tomA encodes a homo-
logue of tomatinase (TomA), a well-characterized enzyme
found in fungal pathogens of tomato [67]. Tomatinase is a
member of the saponinase family of secreted enzymes that
function as glycosyl hydrolases targeting saponins, which are
preformed plant glycosides conferring resistance to pathogen
attack. Tomatinase acts on α-tomatine, a type of saponin that
is used by tomato plants in defence responses [115, 116]. In
the tomato fungal pathogen Septoria lycopersici, TomA has
a dual function, as it hydrolyzes α-tomatine to protect itself
and the degradation products also interfere with the defence
response of the plant [116]. Tomatinase is also required for
the full virulence of two other tomato fungal pathogens,
Fusarium oxysporum f.sp. lycopersici and Cladosporium
fulvum [117, 118]. In contrast, mutants of a tomA homologue
identified in the bacterial tomato wilt pathogen Clavibacter
michiganensis subsp. michiganensis were not compromised
in virulence [115].
The role of TomA in Streptomyces plant pathogenicity remains
unclear. The TomA enzyme from S. scabiei 87–22 was shown
to exhibit activity against α-tomatine, but not against the
potato glycoalkaloids α-chaconine or α-solanine [119]. Given
that S. scabiei is not a known tomato pathogen, the signifi-
cance of the specific activity of TomA towards α-tomatine is
unknown. In addition, a tomA mutant of S. scabiei was unaf-
fected in virulence, and the gene is often lacking in pathogenic
isolates from the environment [14, 113, 119]. It is notable
that tomA in S. scabiei is co-transcribed with an upstream
gene (blgA) encoding a predicted β-glucosidase [119], and
1036
this gene cluster is present in two copies in the genome of
S. turgidiscabies Car8. One copy is located on the PAISt and
shows high identity (98%) with the cluster in S. scabiei, while
the other copy is located elsewhere on the chromosome and
shows reduced identity (87%) with the S. scabiei cluster [18].
Tat-secreted proteins
The twin-arginine translocase (Tat) system is a protein export
pathway that is found in most bacteria and transports fully
folded proteins across the cytoplasmic membrane [120]. In
Streptomyces spp., the system resembles that found in Gram-
negative bacteria in that it consists of three essential compo-
nents – TatA, TatB and TatC [121]. Mutations in the Tat system
components or in Tat-secreted proteins have been shown
to attenuate virulence in some plant pathogens [120, 122].
In S. scabiei 87–22, over 100 proteins have been predicted
to be exported by the Tat system, and a ΔtatC mutant was
severely reduced in virulence on Arabidopsis seedlings [121],
suggesting that one or more Tat-secreted proteins might func-
tion as virulence factors in this organism. Indeed, inactiva-
tion of seven genes encoding proteins that were verified to be
secreted via the Tat system resulted in reduced virulence of
S. scabiei, and several of these genes encode proteins that have
homologues in fungal plant pathogens [121].
Scabin
Scabin is a 22 kDa secreted single-domain enzyme that is
produced by S. scabiei 87–22 and is a predicted virulence
factor in this organism [121, 123]. Scabin is a member of
the mono-ADP-ribosyltransferase (mART) family of toxins,
which includes bacterial toxins such as the cholera toxin
(from Vibrio cholerae), ExoA (from Pseudomonas aeruginosa)
and others (as reviewed by [124, 125]). mART toxins catalyze
the transfer of ADP-ribose from nicotinamide adenine dinu-
cleotide (NAD+) to a target host molecule, leading to func-
tional inactivation of the target. Additionally, most mART
enzymes display NAD+ glycohydrolase (GH) activity [126].
Scabin shares 40 % amino acid identity with the Pierisin
family of mART toxins that target the guanine base in DNA,
leading to cell apoptosis. Purification and characterization
of the Scabin enzyme confirmed that the enzyme exhibits
both GH and ADP-ribosyltransferase activity and targets
guanine-containing DNA substrates [123]. Interestingly,
Scabin showed weak activity against genomic DNA from
S. scabiei and P. aeruginosa, whereas it showed higher activity
against genomic DNA from potato. Currently, the role of this
protein in the virulence of S. scabiei is under investigation.
Plant polymer-degrading enzymes
Secreted plant polymer-degrading enzymes such as cellu-
lases, pectate lyases, lipases and esterases are known viru-
lence factors in several plant-pathogenic bacteria. A recent
comparison of the genome sequences of pathogenic and
nonpathogenic Streptomyces spp. revealed the presence
of several genes that encode predicted plant polymer-
degrading enzymes and are exclusive to the pathogenic
species, suggesting that such enzymes might contribute
to the virulence of these organisms [18]. As discussed
 Li et al., Microbiology 2019;165:1025–1040
previously, there is evidence that suberin stimulates
the production of extracellular cellulolytic enzymes by
S. scabiei and that this contributes to the onset of thaxtomin
production and pathogenicity in this organism [64]. In
addition, a study by Komeil and colleagues showed that
extracellular esterase activity can be detected in cultures of
S. scabiei containing plant polymers, with the highest activity
observed in the presence of suberin [60]. Two genes encoding
putative suberinases, estA and sub1, were detected in the S.
scabiei genome, and while estA was expressed in the pres-
ence of different plant polymers, sub1 was only expressed
in the presence of suberin or cutin [60]. Notably, sub1 (also
called scab_78931) has been identified as a member of the
Streptomyces pathogen-specific genome due to its conserva-
tion in different pathogenic species and its absence from
nonpathogenic species [18]. Although sub1 had previously
been predicted to encode a cutinase [87], it is possible that the
encoded enzyme enables the degradation of suberin in order
to facilitate the penetration of the tuber periderm during
pathogen infection, although this remains to be determined.
Concluding remarks
Research on the molecular genetics of plant-pathogenic Strep-
tomyces spp. has revealed important insights into the strate-
gies that enable them to be highly successful pathogens. The
novel thaxtomin phytotoxins have been identified as essential
pathogenicity determinants produced by several species, and
mobilization of the thaxtomin biosynthetic genes can, in some
cases, lead to the emergence of new pathogenic species. New
evidence suggests that other phytotoxic compounds also
contribute to the development or severity of diseases caused
by Streptomyces spp., including the concanamycin and coro-
nafacoyl phytotoxins, as well as specialized metabolites that
were not previously known to exhibit phytotoxicity. Further
research is needed to clearly establish the role of newly discov-
ered phytotoxins in Streptomyces plant pathogenicity and to
identify the host cell targets. The novel secreted Nec1 protein
is another known virulence factor in scab-causing Strepto-
myces spp., and the identification of its host cell target will
be critical for elucidating the mode of action of this protein
during plant–microbe interactions. In addition, there is
evidence that Tat-secreted proteins contribute to the virulence
phenotype of S. scabiei, and other secreted proteins, along
with phytohormone biosynthetic pathways for the production
of CK, IAA and ET, have a potential role in promoting host
colonization and tissue penetration by Streptomyces patho-
gens. CS is a notoriously difficult disease to control, and thus
a thorough understanding of the molecular mechanisms of
plant pathogenicity will be key to the development of better
management strategies for CS and other diseases caused by
the Streptomyces.
Funding information
This work was supported by a Natural Sciences and Engineering
Research Council of Canada Discovery Grant (grant no. 2018-05155) to
D. R. D. B. J. L. was supported by a China Scholarship Council grant (no.
201603250060).
1037
Conflicts of interest
The authors declare that there are no conflicts of interest.
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