Symbiosis (2022) 86:139–153

https://doi.org/10.1007/s13199-022-00836-1

Role of vertically transmitted viral and bacterial endosymbionts

of Aedes mosquitoes. Does Paratransgenesis influence vector‑borne
disease control?
K. Kaavya1,2 · Jeeja Tharakan3 · C. O. Joshi1 · Embalil Mathachan Aneesh2

Received: 19 July 2021 / Accepted: 27 March 2022 / Published online: 8 April 2022
© The Author(s), under exclusive licence to Springer Nature B.V. 2022

Abstract
Mosquitoes stand as a growing menace to millions of people globally as they are effectual vectors of sundry pathogens. The
resurgence of mosquito-borne diseases across the world shows that the prevailing mosquito control measures are inadequate
to limit the risk of those diseases properly. Aedes species, particularly Aedes aegypti and Aedes albopictus, are the vectors
of arboviruses such as Dengue, Chikungunya, and Zika. Apart from being the vectors of viruses, mosquitoes host various
bacterial species and indulge in symbiotic interactions with them. Several studies have revealed the significant potentialities
of gut bacteria in controlling mosquitoes. A remarkably new initiative called the paratransgenesis approach plays a vital role
in this area of academics. In this study, infectious arboviruses and bacterial endosymbionts of Ae. aegypti and Ae. albopictus
that can endure vertical transmission have been reviewed for comprehending the role in mosquito control. This review can
unravel the major vertically transmitted arboviruses and bacterial species in Aedes mosquitoes, by divulging new strategies
for mosquito control.

Keywords Mosquito · Ae. Aegypti · Ae. Albopictus · Vertical transmission · Paratransgenesis · Arbovirus · Gut bacteria ·
Germline tissues

1 Introduction into 41 genera are observed (Harbach and Besansky 2014).

They are efficacious vectors of diseases like Malaria, Den-
Mosquitoes, the deadliest insects belonging to the family gue, Filariasis, and Haemorrhagic fever, instigating mil-
Culicidae and order Diptera transmit several serious human lions of deaths every single year (Bandyopadhyay et al.
diseases. Globally around 3540 mosquito species falling 2006; Bhatt et al. 2015; Rosenberg et al. 2018). This review
focuses on the vertical transmission (VT) of bacteria and
* Embalil Mathachan Aneesh viruses in Aedes mosquitoes, especially Ae. aegypti and Ae.
aneeshem@uoc.ac.in albopictus. Since infection control and epidemiology chiefly
K. Kaavya depend on transmission mode, a keen scientific study on VT
kaavyakolusu@gmail.com is necessary for comprehending the ecology and evolution of
Jeeja Tharakan pathogens (Mink 1993). Arboviruses’ strategies and meth-
jeejatharakan@gmail.com ods to infest mosquitoes’ organs are to be learned to bring
C. O. Joshi out effective vector control techniques. Random outbreaks
joshiadat@rediffmail.com of these arboviruses are, perhaps, due to their outrageous
capability to survive for extended periods and to carry out
1
Department of Zoology, Christ College Irinjalakuda VT. This review attempts to bring out ingenious perspec-
(affiliated to the University of Calicut), Thrissur, Kerala,
India tives on new strategies for controlling mosquito menace.
2 Further meticulous studies are needed to know more about
Centre for Research in Emerging Tropical Diseases
(CRET‑D), Department of Zoology, University of Calicut, the occurrence and stability of arboviral VT in adverse envi-
Malappuram, Kerala, India ronmental conditions. The gut microbiome of organisms is
3
Department of Zoology, St. Aloysius College Elthuruth, considered as an added organ due to its relevance, diversity,
Thrissur, Kerala, India and composition in the insect gut (Bordenstein and Theis

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140 K. Kaavya et al.

2015; Evans et al. 2013). The same is the case with mos- 2014; Anderson et al. 2014; Ciota et al. 2017; Shroyer 1990;
quitoes as they establish a key role in development, vector Thangamani et al. 2016) (Figs. 1, 2, Table 1).
competence, and susceptibility to infections. Understanding The rate of VT is the ratio of vertically acquired prog-
the common viruses and gut bacteria invading reproductive eny, without considering the number of infected mothers or
tissues and undergoing VT may facilitate new strategies for simply the proportion of females that vertically transmits to
mosquito control. For this extensive study, available arti- at least one of its progeny (Clements 2012). Filial infection
cles and review papers have been retrieved from PubMed, rate represents the rate of infection within a family. The rate
Science Direct, Frontiers, WHO, Science direct, Elsevier of VT varies with many factors both in natural and labo-
websites using keywords such as Mosquito, Ae. aegypti, Ae. ratory conditions, which include mosquito species, its age
albopictus, Vertical transmission, Arbovirus, Gut bacteria, and genetic factors, the strain of virus or bacteria, climate,
and Germline tissues. The authors are restricted to the arti- bloodmeal, and gonotrophic cycle (Beaty et al. 1980; Dutary
cles published in the English language majorly. and Leduc 1981; Hardy et al. 1984; Joshi et al. 2002; Jous-
set 1981; Rosen et al. 1978, 1983, 1989; Saiyasombat et al.
1.1 Vertical transmission 2011; Shroyer 1986, 1990; Tesh 1980). VT rate change with
these determining factors up to a large extent. Among these
Host to host transfer of pathogens occurs by two modes; factors, temperature plays a paramount significance. Low
Horizontal Transmission (HT) and Vertical transmission temperature supports higher infection levels (Hardy et al.
(VT) (Fine 1975). VT or Hereditary transfer refers to the 1980). Some studies (Hardy et al. 1980) suggests that the
parental mode of pathogen transfer, while HT is the non- appropriate temperature is 18°c and not more than 26°c,
parental manner. The pathogen transfer mainly prefers HT while others (Tesh 1980) concluded that no visible variation
however adverse environmental conditions, such as dry sea- with temperature ranging from 20°c - 30°c. Individual vari-
son in the tropics and cold season in the temporal region, ation in the rate of VT was displayed rather than at the level
and application of insecticides curtail host density and of strains in certain studies (Bosio et al. 1992). Individuals
thereby interrupt HT (Leake 1984). To ensure existence or also exhibit variation in rate of VT as a result of genetic
to prevent extinction during adverse conditions when there basis. Considering the age of mosquitoes, scientists have
is a low host population, arboviruses invade germline tis- worked and concluded that older mosquitoes exhibit less
sues and get vertically transmitted to the next generation viral transmission ability (Scott et al. 1994). The infection
(Bhatt et al. 2015; Hogenhout et al. 2008; Lequime et al. possibilities are more even in larval stages than in adult mos-
2016; Lipsitch et al. 1996; Mink 1993). VT, in consequence, quitoes (Billingsley 1990; Lutomiah et al. 2007; Miller and
acts as an important maintenance mechanism (Fine 1975;
Thangamani et al. 2016). So, a more extended desiccation
period provides chances for increased VT (Mourya 1987).
This kind of maintenance mechanism for transferring to
offspring is undertaken by most arboviruses, including the
dengue virus (Bosio et al. 1992; da Costa et al. 2017; Khin
and Than 1983). Mixed-mode transmission is the combina-
tion of both HT and VT. It is observed in both bacteria and
viruses (Ebert 2013; Messenger et al. 1999; Stewart et al.
2005; Turner et al. 1998).
Mechanisms of VT are Transovarial (TOT) and Transo-
vum or Trans-egg transmission. In Transovum or Trans-
egg transmission, the virus adheres to the egg surface at the
time of oviposition (Higgs and Beaty 2005). Amongst the
two modes of VT, in TOT, the virus makes entry into the
oocyte at its development period (Higgs and Beaty 2005),
which is much earlier and more promising than Trans-egg
transmission. Thus, TOT provides more chance for arbo-
viral infection in the next generations (Rosen 1987; Tesh
and Gubler 1975). For successful VT, the virus must enter
the germline of the host mosquito initially. Once the first
set of eggs is produced, virus entry into the ovary is well
promoted at the time of oogenesis. Thus, VT is ensured in Fig. 1  The important methods of pathogen transmission between dif-
gonotrophic cycles ensuing the foremost one (Agarwal et al. ferent hosts

13
Role of vertically transmitted viral and bacterial endosymbionts of Aedes mosquitoes. Does… 141

Fig. 2  The mechanism of the

major types of vertical transmis-
sion (Transegg and Transovarial
transmission)

Table 1  Table representing the vertically transmitted viruses in both Ae. aegypti and Ae. albopictus
Virus Genus Virus Species Reference
Ae. aegypti Ae. albopictus

Flavivirus Dengue DENV1 (Chen et al. 1990; Rosen et al. 1983) (Bosio et al. 1992; Mitchell and Miller
1990; Rosen 1988; Shroyer 1990)
DENV2 (Arunachalam et al. 2008; Khin and (Castro et al. 2004; Martins et al. 2012;
Than 1983; Martins et al. 2012; Thenmozhi et al. 2007)
Mourya et al. 2001)
DENV3 (Arunachalam et al. 2008; Martins (Martins et al. 2012)
et al. 2012; Joshi et al. 2002)
DENV4 (Hull et al. 1984) (Maia et al. 2019)
Zika Virus (Ciota et al. 2017; Thangamani et al. (Guo et al. 2020)
2016)
Yellow Fever Virus (Aitken et al. 1979; Beaty et al. 1980)
Kamiti River Virus (Lutomiah et al. 2007)
Murray Valley Encephalitis Virus (Kay and Carley 1980)
Japanese Encephalitis Virus (Rosen et al. 1978)
West Nile Virus (Baqar et al. 1993) (Baqar et al. 1993)
Alphavirus Chikungunya Virus (Agarwal et al. 2014; Chompoosri (Chompoosri et al. 2016)
et al. 2016)
Orthobunyavirus San Angelo Virus (Shroyer 1986; Tesh and Shroyer 1980)

Lehane 1993); that is the focal point behind it. Due to the
development of peritrophic matrix just after blood feeding
in adult mosquitoes, the viruses arriving the adult host body
via bloodmeal might not easily escape through peritrophic
membrane to make infection. While, viruses infecting larvae
find their way directly into midgut which increase the pos-
sibilities for infection (Lutomiah et al. 2007).
Experimental conditions can also alter the rate and pat-
tern of VT (Lutomiah et al. 2007). Natural conditions are
better than laboratory conditions for sufficient infection that
leads to VT (Anderson and Main 2006). Even though all the
suitable natural conditions are available, VT is less observed
in the initial gonotrophic cycle (Tesh 1984). Viruses entering
via bloodmeal needs surplus time to incorporate into ovaries.
So the transmission happens only after further gonotrophic
cycles (Agarwal et al. 2014). The rate of VT increases with
each gonotrophic cycle (Angel and Joshi 2009; Flores et al.
2010; Olson et al. 2000; Pierro et al. 2003; Rosen et al.
1989) and it is greater in the 3rd gonotrophic cycle (Diallo
et al. 2000). An epitome of the gradual increase in VT is;
La cross virus in Ae. triseriatus (Miller et al. 1979). VT
rate remains stable after the second generation (Joshi et al.
2002). Transmission retains up to three generations and
gradually decreases. And further, VT decreases with each

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142
cycle (Beaty et al. 1980). Considering the varied outcomes
of diverse works, it can be conferred that the chance for viral
invasion into the ovaries starts from the second gonotrophic
cycle leading to high rate of VT during and after second
gonotrophic cycles and will gradually subside later after few
cycles of transmission.
1.2 Vertical transmission of virus
The important arboviruses infecting Aedes mosquitoes
include Chikungunya virus (CHIKV) belonging to Alphavi-
rus, Dengue virus (DENV), Zika virus (ZIKAV), Yellow
fever virus (YFV), West Nile Virus (WNV), Japanese
Encephalitis Virus (JEV), and Kunjin Virus belong to Fla-
vivirus causing serious diseases like Chikungunya, Dengue
fever, Yellow fever, West Nile fever, Japanese Encephalitis,
and Encephalitis.
Several studies agree that the virus infecting via blood-
meal undergoes replication in posterior midgut epithelial
cells (Olson et al. 2000; Pierro et al. 2003; Romoser et al.
2004; Smith et al. 2007). After that, the transfer of the
virus from the midgut to hemocoel and secondary tissues
takes place. Dissemination through hemolymph gradu-
ally increases with time after infection which may lead to
delayed VT (Dubrulle et al. 2009). Many viruses occur to
be infecting the ovaries of Aedes mosquitoes (Larsen and
Ashley 1971). To survive in the ovaries, the viruses should
bear stressful conditions all through the development of the
host mosquito (Hardy et al. 1983).
VT is chiefly relied upon by alphavirus and flavivirus
(Baqar et al. 1993; Rosen et al. 1989; Tesh and Gubler
1975). The major flaviviruses including DENV, YFV, JEV
(Japanese Encephalitis virus), St. Louis Encephalitis virus,
WNV, Tick-borne Encephalitis virus undertake VT in both
natural and experimental conditions (Adams and Boots
2010; Blitvich and Firth 2015; Bolling et al. 2015; Tesh
et al. 2016). Natural VT has been reported widely. Though
the focus on this by experiments is vital, studies on VT of
alphavirus in laboratory conditions are scanty (Mourya
1987; Vazeille et al. 2009). In experimental studies, the pro-
cedures and associated factors contribute to the transmission
variably. The mode of viral entry can make any alteration
in viral infection susceptibility, which appears to be true for
DENV 2 and DENV 3 in Ae. aegypti (Gubler et al. 1979)
and Ae. albopictus (Gubler and Rosen 1976). The intratho-
racic infection makes viral infection more stable than oral
infection (Hardy et al. 1978). Way of viral incorporation can
also influence the VT rate. Needle inoculation was found to
be less reliable for TOT (Saiyasombat et al. 2011), while it
has been successful in some other studies (Chandler et al.
1990; Tesh 1980; Turell 1988). The more successful viral
infection route is oral than intrathoracically (Smith et al.
2007).
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K. Kaavya et al.
In Transovarial transmission, the virus incorporates into
the ovary and gets transferred from mother to progeny or
next-generation, whereas in Transovum transmission, the
virus infects the eggs. Efficient and stable VT of the virus
ensues by invading follicles and carrying out TOT than
trans-egg transmission (Saiyasombat et al. 2011). TOT rate,
stability, and ability to follow TOT are higher in mosquitoes
that are already infested with vertically transmitted viruses
(Shroyer 1986). The entry of the virus into ova is essential
for the VT to occur (Diallo et al. 2000; Miller et al. 2000;
Tesh and Cornet 1981). Inside eggs, most viruses are highly
adaptable to survive for a longer period (Beaty et al. 1980).
An example of the Trans-egg mode of VT is the transmis-
sion of the flaviviruses, JEV and SLE in Ae. albopictus mos-
quitoes (Rosen 1988).
TOT does not occur for all arboviruses (Watts and
Eldridge 1975). Even susceptibility to infection varies for
each viral strain (Tesh et al. 1976). Likewise, certain strains
are more effectual in transmission (Tesh 1980; Tesh and
Shroyer 1980), while others are not. Many viruses estab-
lished a low rate of TOT in mosquitoes (Rosen et al. 1978;
Tesh 1980). TOT is mainly preferred by flaviviruses (Sai-
yasombat et al. 2011). While contrary to other arboviruses,
Flavivirus gets inadequately transmitted employing TOT,
as well demonstrated in many studies (Aitken et al. 1979;
Beaty et al. 1980; Francy et al. 1981; Hardy et al. 1984;
Kay and Carley 1980; Rosen et al. 1978). Additionally, fla-
vivirus also prefers transovum transmission (Rosen 1988).
So far, different works have confirmed the TOT of Dengue
virus, Japanese Encephalitis Virus, La Crosse virus, San
Angelo Virus, West Nile Virus, and Yellow Fever Virus in
Aedes mosquitoes. VT studies are mostly done on DENV
than other arboviruses. TOT of DENV serotypes in both
Aedes species under natural and laboratory conditions were
done (Chen et al. 1990; De Figueiredo et al. 2010; Martins
et al. 2012; Mitchell and Miller 1990; Rosen 1988; Rosen
et al. 1985). The VT rate of DENV 1 is higher among all
other DENV serotypes (Lequime et al. 2016). The VT rate
of DENV is greater for Ae. albopictus than for Ae. aegypti
(Bosio et al. 1992; Lequime et al. 2016; Rosen et al. 1983).
While the converse is the case in studies by Lee (Lee and
Rohani 2005; Lee et al. 1997).
1.3 Vertical transmission of bacteria
Bacteria observed most commonly in all Aedes spp. are
considered as the Core Microbiota of mosquitoes (Dada
et al. 2014; Dennison et al. 2014; Guégan et al. 2018). Pro-
teobacteria, Bacteroidetes, Firmicutes, and Actinobacteria
phyla represent the major microbiota of adult mosquitoes
(Mancini et al. 2018; Minard et al. 2013; Wang et al. 2011).
It was exactly true for both Ae. aegypti and Ae. albopictus
(Bennett et al. 2019). Among the 4 phyla, Proteobacteria
Role of vertically transmitted viral and bacterial endosymbionts of Aedes mosquitoes. Does…
dominates in the gut and other tissues of Aedes, Anopheles,
and Culex mosquitoes (Mancini et al. 2018; Pidiyar et al.
2004; Rani et al. 2009; Zouache et al. 2011). Enterobacter,
Escherichia, Klebsiella, Pseudomonas, and Serratia occur
to be the common bacterial genera in Aedes, Anopheles, and
Culex mosquitoes (Demaio et al. 1996; Pidiyar et al. 2002;
Touré et al. 2000). Mosquitoes acquire most of the bacterial
microorganisms from breeding water at their larval stage
(Boissière et al. 2012; Coon et al. 2016; Coon et al. 2014;
Duguma et al. 2015; Duguma et al. 2013; Gimonneau et al.
2014; Straif et al. 1998; Wang et al. 2011). Microbes in the
aquatic habitat which enter the mosquito larval gut have
a profound role in its survival, growth, and development.
Microbiota shows an indelible role in the development of
host mosquitoes (Coon et al. 2014, 2016, 2017). It is exem-
plified by many researchers through observing the develop-
ment of mosquitoes after the removal of their microbiota. In
most cases, larvae fail to develop entirely (Coon et al. 2014;
Thongsripong et al. 2018). Not only in the development
and survival of its host mosquitoes but also for its patho-
gen transmission abilities, these gut microbiomes extend
sufficient impact. The vector competence of mosquitoes is
largely influenced by its microbiota (Apte-Deshpande et al.
2012; Cirimotich et al. 2011; Dodson et al. 2014; Dong
et al. 2012; Engel and Moran 2013; Jupatanakul et al. 2014;
McMeniman et al. 2009; Okech et al. 2007; Pumpuni et al.
1993, 1996; Ramirez et al. 2012, 2014; Takken et al. 2013).
The susceptibility of mosquitoes to pathogens seems to be
lower due to the influence of gut microbiota (Bahia et al.
2014; Cirimotich et al. 2011; Dong et al. 2012; Xi et al.
2008).
More bacterial diversity is observed in Ae. aegypti in
comparison with Ae. albopictus (Mancini et al. 2018;
Minard et al. 2013). A conceivable reason for this might be
the high tolerance of Ae. aegypti to bacterial symbiotic asso-
ciations (Minard et al. 2013). Bacteria not only invade the
mosquito gut, but also invade salivary glands, malpighian
tubules, and germline tissues (Chavshin et al. 2015; Gusmão
et al. 2010; Mancini et al. 2018; Muturi et al. 2018; Sharma
et al. 2014). VT of bacterial symbionts is made possible by
invading and manipulating the reproductive organs of insects
(Dale and Moran 2006; Engelstädter and Hurst 2009; Moya
et al. 2008). A palpable example of it is Wolbachia which
incorporates into reproductive tissues and manipulates host
reproduction for VT (O'Neill et al. 1992; Rousset et al. 1992;
Werren et al. 2008).
Asaia and Wolbachia were detected from the reproduc-
tive organs of mosquitoes (Ricci et al. 2012). Wolbachia
invading the ovary successfully undergo VT in mosquitoes
(Fraser et al. 2017; Hughes and Rasgon 2014; Jiggins 2017).
A holistic view of the bacterial consortium associated with
the reproductive tissues of Ae. aegypti and Ae. albopictus
has been brought out by the work of Mancini (Mancini et al.
143
2018). Actinobacter, Elizabethkingia, Pseudomonas, Ochro-
bactrum, Sphingomonas genera occur in the reproductive
tissues of Ae. aegypti while Wolbachia, Serratia, Cupriavi-
dus, and Sphingomonas genera in the reproductive tissues of
Ae. albopictus. Zouache and co-researchers (Zouache et al.
2009) carried out relevant work on the bacterial consortia
in reproductive and somatic tissues of Ae. albopictus. They
detected the incidence of Wolbachia, Mesorhizobium, and
Eubacteria genera from the reproductive tissues. And con-
cluded that Proteobacteria invades both somatic and repro-
ductive tissues of Ae. albopictus. Microbiota in the repro-
ductive system is more heterogeneous than in other organs.
1.4 Bacteria undergoing vertical transmission
VT is the main mode of transmission for insects’ primary
symbionts while secondary symbionts that get horizon-
tally acquired also endure VT (Dale and Moran 2006). VT
is relied upon by mosquito midgut bacteria in many cases
(Favia et al. 2008; Straif et al. 1998). Transovarial mode of
VT is undertaken by bacterial microbes such as Wolbachia,
Rickettsia, Spiroplasma, Buchnera, and Hamiltonella (Bru-
min et al. 2012; Dykstra et al. 2014; Herren et al. 2013;
Newton et al. 2015; Wilkinson et al. 2003). In An. gambiae,
Elizabethkingia meningoseptica was observed to be under-
going VT by colonizing reproductive tissues like the ovary
(Akhouayri et al. 2013). Elizabethkingia carryout various
transmission routes such as VT, HT, and transtadial trans-
mission (Akhouayri et al. 2013; Coon et al. 2014; Ngwa
et al. 2013). Endosymbionts with VT or maternal route of
transmission provide some benefits to hosts and modify
hosts’ reproduction for its own survival (Stouthamer et al.
1999; Werren 1997). Mosquitoes entertain VT by releasing
back their acquired bacteria to breeding water during egg-
laying so that larvae persisting in water can acquire it (Coon
et al. 2016).
1.4.1 Wolbachia
Wolbachia, an Alphaproteobacterium strictly gets mater-
nally transmitted (Stouthamer et al. 1999; Tram et al. 2003;
Zug and Hammerstein 2015) which is achieved by inducing
Cytoplasmic Incompatibility (CI), that is sperm-egg incom-
patibility (Clancy and Hoffmann 1998; Dobson et al. 2001;
Jiggins 2017; Rousset and Raymond 1991; Sinkins et al.
1995; Sinkins 2004; Turelli and Hoffmann 1995; Werren
et al. 2008). Due to CI, Wolbachia-infested females get a
reproductive advantage (Turelli and Hoffmann 1995; Wer-
ren et al. 1995) and infected males do not produce viable
offsprings if they mate with an uninfected female, embryos
die at an early stage (Bahia et al. 2014; Chavshin et al. 2015;
Gusmão et al. 2010). Even though Wolbachia invades male
reproductive tissues, they avoid paternal transmission by
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144
getting eliminated at the time of spermatogenesis itself
(Binnington and Hoffmann 1989; Bressac and Rousset 1993;
Clark et al. 2002; Ijichi et al. 2002).
Microorganisms harness various routes to invade repro-
ductive tissues and further support VT. Wolbachia invades
the germinal tissues by incorporating into the posterior
region of oocytes to invade the pole cells (Hadfield and
Axton 1999; Kose and Karr 1995). Invasion into germinal
tissues happens mainly during oogenesis (Fast et al. 2011;
Newton et al. 2015). VT of Wolbachia is detected in Aedes
and Anopheles mosquitoes (Bian et al. 2013; Coon et al.
2014; Hoffmann et al. 2011, 2014). In both Ae. aegypti and
Ae. albopictus, Transovarial mode of VT is the utmost prom-
ising mode of VT (Dobson et al. 2001, 2004; Sinkins et al.
1995; Xi et al. 2005). Wolbachia is extensively studied and
well examined to be used in vector control by transinfection
(Bourtzis et al. 2014; Hughes and Rasgon 2014; McGraw
and O'neill 2013). Ae. aegypti species do not possess natu-
ral Wolbachia infection (Ruang-areerate and Kittayapong
2006). Transinfection of Wolbachia into Ae. aegypti decrease
its VC for dengue virus (Bian et al. 2010; Hoffmann et al.
2011; Mohanty et al. 2016; O'Neill et al. 1992; Saridaki
and Bourtzis 2010), Chikungunya virus (Aliota et al. 2016b;
Moreira et al. 2009) and Zika virus (Aliota et al. 2016a).
Experiments verified Wolbachia’s efficiency in averting
the replication of viruses, including Dengue, Chikungunya,
Zika, and Yellow fever virus (Aliota et al. 2016a; Bian et al.
2010; Frentiu et al. 2014; Moreira et al. 2009; Van den Hurk
et al. 2012). Due to Wolbachia’s immense role in prevent-
ing sundry pathogenic infections in mosquitoes (Bian et al.
2010; Moreira et al. 2009), it may be implemented mag-
nificently in vector control initiatives (Ricci et al. 2012)
in the very near future with new methods to culture them
in vitro and introduce Wolbachia in wild mosquito popula-
tion successfully.
1.4.2 Asaia
Asaia, an Alphaproteobacterium gets transmitted in vari-
ous manners, such as horizontal, vertical, venereal, and
transstadial transmission (Crotti et al. 2009; Damiani et al.
2008; Favia et al. 2007, 2008). Asaia efficiently invades and
occupies the gut, salivary glands, and reproductive tissues
of mosquitoes with the aim of undergoing VT (Capone
et al. 2013; Damiani et al. 2008, 2010; Favia et al. 2007).
VT of Asaia is detected in Ae. aegypti and Anopheles mos-
quitoes (Favia et al. 2007). Asaia impedes the transmis-
sion of Wolbachia in Anopheles mosquitoes (Guégan et al.
2018; Hughes et al. 2014; Rossi et al. 2015). And intrigu-
ingly Asaia fails to infect the reproductive tissues of Ae.
albopictus and Culex quinquefasciatus, which are naturally
infected with Wolbachia (Rossi et al. 2015). Shreds of evi-
dence reveal the venereal transmission of Asaia whereby
13
K. Kaavya et al.
it gets transmitted from male to female during mating
(Beard et al. 2002; De Freece et al. 2014; Favia et al. 2007).
Paratransgenesis approaches utilize Asaia for controlling
mosquito-borne diseases (Favia et al. 2008), especially to
control Plasmodium infection because of its importance in
the development of Anopheles mosquitoes and as well as its
ability to produce anti-plasmodium molecules (Riehle and
Jacobs-Lorena 2005; Riehle et al. 2007; Saldaña et al. 2017;
Yoshida et al. 2001).
1.4.3 Serratia
Serratia, a Gammaproteobacteria member colonizes the
gut, salivary glands, and germline tissues of mosquitoes,
including Aedes and Anopheles (Gonzalez-Ceron et al.
2003; Mancini et al. 2018). Transmission modes include
horizontal, vertical, and transstadial in their host species.
VT is detected in Anopheles mosquitoes (Wang et al. 2017),
whereas transstadial mode of transmission is confirmed in
Ae. aegypti (Woodring et al. 1998). Works of Apte-Desh-
pande (Apte-Deshpande et al. 2012, 2014) bring out some
more suppositions, such as the constructive influence of Ser-
ratia odorifera towards the susceptibility and replication of
infectious viruses, including DENV and CHIKV. Thus, the
cultivable bacteria justify the criteria of a fruitful candidate
for paratransgenesis.
1.5 Paratransgenesis
Manipulating symbiotic microbes to act counter to patho-
genic infections in insects is a new approach in vector con-
trol, known as paratransgenesis (Beard et al. 1993; Boissière
et al. 2012; Dong et al. 2009; Wang et al. 2012; Wang and
Jacobs-Lorena 2013; Yoshida et al. 2001). The technique
aims at the preclusion of vector-borne diseases by putting
control over vector population via transgenesis of its sym-
bionts. Genetic manipulation of the symbionts and utiliz-
ing it as an expression vector is the elementary principle.
Transgenic symbionts are developed with proteins having
abilities to prevent disease transmission in corresponding
vectors. Within the vectors, the successfully introduced and
thus established transgenic symbionts negatively encourage
disease transmission.
Vector competence of mosquitoes is the focal target of
the genetically modified symbiont. Symbionts are manip-
ulated and altered in such a way that it limits the vector
competence of the mosquito. Stable association between the
symbiont and host is the utmost important factor (Wang and
Jacobs-Lorena 2013). The symbionts with obligate relation-
ship and stable association with the vector, or those who
support the vector for its fitness, and can undergo VT are
thus the best candidates of paratransgenesis. Symbionts uti-
lized for the paratransgenesis approach should satisfy some
Role of vertically transmitted viral and bacterial endosymbionts of Aedes mosquitoes. Does…
characteristics; symbiont needs to be easily cultured in in-
vitro conditions, malleable to genetic modifications (Wang
and Jacobs-Lorena 2013), express the introduced effector
molecules with the desired action, colonize and survive in
the host body without any fitness cost, transmit transsta-
dially, and grow in culture (Bahia et al. 2014; Favia et al.
2007). Easily cultivable symbionts in lab conditions like
Asaia (Favia et al. 2007), and Pantoea (Bisi and Lampe
2011; Straif et al. 1998) are the prominently studied ones.
The genetic manipulation must not negatively (Bisi and
Lampe 2011; Straif et al. 1998) affect the survival and fit-
ness of the bacterial symbionts, and should remain stable
after the modification also (Wang and Jacobs-Lorena 2013).
Even more than one transgenic symbionts can be introduced
into a vector population to inhibit the pathogenic propulsion
in various ways (Fang et al. 2011). Bacteria invading the
mosquito gut can be modified to be employed in vector con-
trol by paratransgenesis interventions (Boissière et al. 2012;
Riehle et al. 2007). Asaia, Enterobacter, Pantoea, Serratia,
and Wolbachia provide these characteristics and are hence,
used in these approaches (Bahia et al. 2014; Eappen et al.
2013; Favia et al. 2008; Gonzalez-Ceron et al. 2003; Yoshida
et al. 2001). And many new bacterial symbionts have been
utilized for this approach to control vector-borne diseases
(Djadid et al. 2011), Wolbachia provides inhibitory effects
on the replication and thus spread of many viral infections.
So, transinfection of Wolbachia into mosquitoes in labora-
tory conditions proved to be a good method. It was stud-
ied and found to be working against plasmodium, dengue
virus, yellow fever virus, and chikungunya virus (Bian et al.
2013; Blagrove et al. 2013; Hughes et al. 2011; Kambris
et al. 2009; Moreira et al. 2009). In the future, the barrier
for culturing Wolbachia strains in vitro may lead to great
contributions at the application level.
Beyond bacteria, other microorganisms like viruses and
fungi associated with mosquitoes can also be applied in par-
atransgenesis means (Chavshin et al. 2012; Ren et al. 2008;
Wang et al. 2011). Effector molecules are the backbone of
this method, as it helps in blocking the disease transmission
without causing any other non-target effects. It works by
interacting with the host vector or pathogen to inhibit the
invasion of the disease-causing pathogen.
The technique has been most efficiently employed and
continues to be an effective strategy for malaria control
widely by modifying bacterial symbionts to produce anti-
parasitic molecules in order to confer resistance against
plasmodium infection in Anopheles mosquitoes (Wang
et al. 2012; Wang and Jacobs-Lorena 2013). The bacteria
Pantoea agglomerans act as a good candidate for the same.
Anti-malarial effector proteins such as SM1(salivary and
midgut peptide 1, defensins, cecropins, and scorpine, pro-
duced by several bacterial symbionts showed effectiveness
against Plasmodium falciparum development. SM1 inhibits
145
Plasmodium infection with its specific binding to midgut
epithelium and salivary glands (Bisi and Lampe 2011; Fieck
et al. 2010; Moreira et al. 2002). The effector molecules
against malaria infection, with anti-plasmodium abilities,
belong to different classes. Defensins and cecropins are pro-
duced from the immune system of mosquito, scorpine toxin
derived from other species, and molecules like SM1 and
mutant phospholipaseA2 which binds and block the recep-
tors of pathogen entry. In Aedes mosquitoes, effectors such
as cecropins are shown to prevent the transmission of den-
gue, and chikungunya. In order to prevent dengue infestation
in Ae. aegypti, Metarhizium anisopliae fungus transformed
to produce scorpine effector molecules was observed to be
successful (Durvasula et al. 1999; Fang et al. 2011). In the
future, improved introduction and establishment of these
engineered transgenic symbionts into wild mosquito popu-
lation may outcompete other control strategies and be a suc-
cessful method with effectiveness against a wide variety of
host mosquitoes and pathogens.
Further studies are required to find out all the possible
microbiota with the potential for paratransgenic approaches
to establish a strong vector control.
2 Conclusion
Mosquitoes are inhabited by diverse groups of viruses and
bacteria in reproductive tissues and are highly important in
their fitness, survival, and disease transmission. Acquiring
details about the vertically transmitted viruses and bacteria
of mosquitoes can open up the chances of bacterial adapta-
tions for controlling mosquito behavior.
We reviewed the available research articles on VT of
the microbial inhabitants of mosquitoes. We observed that
among the diverse modes of transmission, the probable
chance for VT intensify when hostile circumstances for other
modes exist. We examined all the possible factors affecting
mechanism of VT and the wide varieties of microbes car-
ryingout the VT pathway. Understanding all the possible
transmission modes of arboviruses is vital when methods
of human infections evolved devastatingly. Earlier studies
have already demonstrated the various role of gut bacteria
in mosquitoes, but the studies focusing on bacteria in Aedes
mosquitoes’ reproductive tissues are few. Even though Ae.
aegypti and Ae. albopictus are important vectors seen in
India, studies highlighting their germline bacteria, and VT
is nearly lacking. VT method gets thoroughly established
in an adult only after the first gonotrophic cycle and after
several rounds of transmission, it will decrease. The main set
of arboviruses undertaking VT are DENV, WNV, JEV, and
CHIKV, St. Louis Encephalitis virus and the bacterial gen-
era are Wolbachia, Asaia, Serratia, Rickettsia, Spiroplasma,
Buchnera, Hamiltonella and Elizabethkingia.
13
146
Evidences of several arboviruses choosing VT as an
important maintenance mechanism at altered rates in dif-
ferent mosquito species bring out the evolutionary changes
involved for better diseases transmission abilities through
suitable host species. This finding highlights that these
adaptations may lead to advanced vector abilities and
hence, further disease outbreaks. Despite the enormous
number of works on mosquito gut bacteria and mosquito-
borne viral diseases, studies on the bacteria and viruses in
germline tissues that undergo VT in Aedes mosquitoes are
scarce. Understanding the vertically transmitted viral and
bacterial species and their specializations to safely inhabit
mosquitoes may uncover idealistic and promising mosquito
control methods. The use of gut bacteria in paratransgenic
approaches paved the ways to develop innovative techniques
to scourge mosquito-borne diseases. Gut bacteria, especially
Wolbachia and Serratia have been very well utilized in para-
transgenesis. A very relevant future goal is the identification
of new microbes with required characteristics to be utilized
for paratransgenesis techniques and practical application of
the approach with successful strategies for introduction of
the transgenic mosquitoes into wild population clearing all
the limiting constrains.
Acknowledgments The authors would like to thank Department of
Zoology, University of Calicut for the laboratory facilities provided.
The authors offer sincere gratitude to the University Grants Commis-
sion, Government of India for financial support of the author Kaavya
K. in the form of UGC Junior Research Fellowship.
Code availability Not applicable.
Data availability Data sharing not applicable to this article as no data-
sets were generated or analysed during the study.
Declarations
Conflict of interest The authors declare that they have no conflict of
interest.
Ethics approval This article does not contain any studies with human
participants or animals performed by any of the authors.
Consent to participate Not applicable.
Consent for publication Not applicable.
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