Vibrionaceae

Vibrio
Comma-shaped, curved gram-negative rods
Most vibrios have polar flagella
Vibrious have various pili that is important for
virulence (toxin co-regulated pilus in V.cholerae)
O polysaccharide of LPS is used to subdivide vibrio
species into serogroups (140 serogroup of
V.cholerae,13 O serogroups of
V.parahaemolyticus,7 O serogroups of V.vulnificus)
V.vulnificus and non-O1 V.cholerae produce acidic
polysaccharide capsules that is important for
disseminated infections.
 vibrio
Grow on a variety of simple media within a
broad temperature range (14◦C -40 ◦C)
All species require salt for growth
(halophilic)
V.cholerae can grow on most media
without added salt
Vibrio tolerate a wide range of pH (6.5-9)
Are susceptible to stomach acids
 Vibrio cholera
Structure : Comma-shaped,
curved gram-negative rods,(2-4µm
long),
motile by a polar flagellum,
toxin co-regulated pilus (type IV pilus)
polysaccharide capsules (only in non-
O1 groups ),
unusual LPS (absence of KDO) ,
facultative anaerobe
 Vibrio cholerae
Culture : grows well at 37°C for 24 hours and
produces yellow colonies on TCBS (thiosulfate
–citrate -bile-sucrose ) agar ,grows in alkaline
peptone water (6-8 hours), grows on TTGA
( telluride –tourocolate- gelatin agar)

Growth characteristics: Simple nutritional

requirements ; don’t require salt for growth but
can tolerate it. Grows at very high PH (8.5-
9.5), optimum pH: 7-9, are killed by acid.
- Ferments sucrose and mannose .
- Is oxidase (+) ,susceptible to O/129 (2,4-
diamini-6,7-diisopropylpteridine)
 Vibrio cholerae (Antigenic structure )
heat-labile flagellar H antigen
O cell wall antigens ( strains subdivided into more than
140 serogroups)
Biotypes : Cholera (O1 serotype), El -Tor (O1 serotype) ,
Albensis (NAG), Proteus(NAG)

Strains of O group1 and 139 cause classic and El-Tor

cholera; non-O1/O139 causes cholera-like disease.

V.cholerae serogroup O1 is further subdivided into

serotypes (inaba, ogawa, hikojima) serotype ogawa
(express A and b antigen), serotype Inaba (express A
and C antigens), Hikojima (express A, B and C antigens)
strains can shift between Inaba and Ogawa, with
Hikojima a transitional state in which both Inaba and
Ogawa antigens are expressed
 Vibrio cholerae
Antigenic structure(cont.)
Classic cholera (responsible for first 6
pandemics) and El Tor ( responsible for
7th pandemic)

The El Tor biotype produces a

hemolysin, is VP(+), resistant to
polymyxin B and resistant to mukerjee
type IV bacteriophage.

V.cholera O139 have a polysaccharide

capsule like non-O1.
Virulence factors of V. cholerae O1 and O139
Cholera toxin :a heat-labile enterotoxin, interacts with G
protein that control adenylate cyclase, leading to the
catabolic conversion of ATP to cAMP. This results in a hyper
secretion of water and electrolytes.

Toxin co-regulated pilus: adherence to intestinal mucosal

cells; binding site for CTXø bacteriophage ( encoded genes
for cholera toxin)

Accessory cholera enterotoxin : increases intestinal

secretion

Zonula occludens toxin :loosens the tight junctions of small

intestine increases intestinal permeability

Chemotaxis protein: adhesin factor

Neuraminidase : modifies cell surface to increase GM1

binding sites for cholera toxin
 Pathogenesis of V.cholerae
- Bacteriophage CTXΦ encodes the genes for :
Two subunits of cholera toxin (ctxA and ctxB genes)
Gene for accessory cholera enterotoxin(ace gene)
Gene for zonula occludens (zot gene)
Gene for chemotaxis proteins ( cep gene)
- Chromosomal CTX virulence cassette and ToxT (a
regulating protein) are controlled by ToxR protein that
responds to PH and temperature.
- Lysogenic Bacteriophage CTXΦ binds to the toxin co-
regulate pilus (tcp) and moves into the bacterial cell and
integrates into V.cholerae genome.
- Adherence of V.cholerae to mucosa cell layer:
1- toxin co-regulated pili (controlled by ToxT protein)
2- chemotaxis proteins
 Pathogenesis of V.cholerae
Cholera toxin is a complex A-B toxin (similar to E.coli
LT toxin)
5 B subunits bind to GM1 gangliosides receptor on epithelial
cells of intestinal epithelial cells, after endocytosis A subunit
translocates across the membrane of vacuole. A subunit has
ADP-ribosyltransferase activity and interact with Gs
membrane protein that regulate adenylate cyclase. Leading to
the catabolic conversion of ATP to cAMP, increase in cAMP
levels, with enhanced hypersecretion of water , chloride and
decrease absorption of Na and Cl (watery diarrhea)
zonula occludens and accessory cholera enterotoxin
produce significant diarrhae in absence of cholera toxin
(in serotype O1)
 Mechanism of Cholera toxin
 Chromosomally-encoded;
Lysogenic phage conversion;
Highly conserved genetic
sequence
 Reduction of disulfide bond in A-
subunit activates A1 fragment that
ADP-ribosylates guanosine
triphosphate (GTP)-binding protein
(Gs) by transferring ADP-ribose
from nicotinamide adenine
dinucleotide (NAD)
 ADP-ribosylated GTP-binding
protein activates adenyl cyclase
leading to an increased cyclic AMP
(cAMP) level and hypersecretion of
fluids and electrolytes
 1 2

Mechanism
of Action of
Cholera
Toxin

3 4
NOTE: In step #4,
uptake of Na+ and Cl-
from the lumen is also
blocked.

HCO3- = bicarbonate
which provides
buffering capacity.
Mechanism of Action of Cholera Toxin
 Vibrio cholera ( epidemiology)
Serotypes O1 is responsible for major pandemics (7 worldwide
epidemics) with significant mortality in developing countries; O139
can cause similar diseases and may cause a pandemic (1992-
1993 in Bengal)

Is endemic in India and southeast Asia.

Organism found in estuarine and marine environments

Organism can multiply freely in water

Bacterial levels increase in contaminated waters during the warm

months

Spread by consumption of contaminated food or water,

asymptomatically infected humans are reservoir ( spread vibrio for
4 weeks after infection by stool)

Direct person-to-person spread is rare because the infectious dose

is high ( because most organisms are killed by stomach acids
 Vibrio cholera
Pathogenesis :
- Is pathogenic only for humans.

- When vehicle is water, V.cholera>1010 is need for

disease , and when vehicle is food >102-104.

- Cholera is not a invasive infection and do not reach

to bloodstream.

- Attach microvilli of the brush border of epithelial

cells.
 V.Cholerae (clinical findings )
About 60-75% 0f infections are asymptomatic
Incubation period is 1-4 days

Cholera : begins with an abrupt onset of

watery diarrhea (rice water stool)
vomiting
and can progress to severe dehydration,
metabolic acidosis (bicarbonate loss)
hypokalemia, and hypovolemic shock (potassium
loss),
cardiac arrhythmia
renal failure
the mortality rate is between 25-60% in untreated
patients and less than 1% in treated patients.
V.Cholerae (clinical findings )
Gastroenteritis : milder forms of
diarrheal disease can occur in toxin-
negative strains of V.cholerae O1 and
in non-O1 serotypes

Extraintestinal infections :septicemia

( in patients with liver disease or
hematologic malignancies
 V.cholera(Diagnosis)
Specimens : stool on Carry Blair transport
medium; Cary-Blair transport media must be
refrigerated in delayed specimen transports
Microscopic examination of stool : nonproductive
because of dilution of water diarrhea, darkfield or
phase contrast shows motile vibrios.
Culture : should be performed early in course of
disease with fresh stool specimens ; alkaline
peptone broth (PH 8.6), TCBS agar , MacConkey
agar, blood agar
Identification, serotyping and biotyping: by
selective biochemical tests and by serotyping
using polyvalent anti O group 1 antisera ,anti O
group 139 antisera, serogrouping Ogawa,Inaba
and Hikojima
 V.Cholera
Treatment, prevention, and control
Treatment : fluid and electrolyte replacement are
crucial
Sodium chloride (3.5 g/L)
+ Potassium chloride (1.5 g/L)
+ Rice flour (30-80g/L)
+ Trisodium citrate (2.9 g/L)

Antibiotics reduce the bacterial burden and exotoxin

production , as well as duration of diarrhea

Doxycicline (adults) ,SXT (children), or furazolidone

(pregnant women) is administrated

Improved hygiene is critical for control

Prevention: Combination inactivated whole cell and

cholera toxin B subunit vaccines provide limited
protection; other vaccines are in development
 Vibrio parahemolyticus
Structure : Curved gram-negative , facultative
anaerobe, fermenter, simple nutritional
requirements but requires salt for growth

Virulence factor :thermostable direct hemolysin

(TDH or kanagawa hemolysin): an entertoxin
that induces chloride ion secretion in epithelia cells
by increasing intracellular calcium ;produces β-
hemolytic colonies on agar media with human
blood .

Epidemiology : Organism found in estuarine and

marine environment
- Associated with consumption of contaminated
shellfish
- a major pathogen in countries where raw fish is
eaten
Vibrio parahemolyticus (clinical diseases)
Gastroenteritis: range from self- limited
diarrhea to a mild, cholera-like illness.
Incubation period : 5-72 hours ( mean 24
hours)
Symptoms: an explosive onset of watery
diarrhea ( non blood or mucus except in
severe cases) and nausea ,vomiting,
abdominal cramps ,headache , and low- grade
fever for 72 hours

Wound infection : Associated with exposure to

contaminated seawater
 Vibrio parahemolyticus

Diagnosis: culture on TCBS

Treatment ,prevention ,and control:

- self-limited disease ,although antibiotics
can shorten length of symptoms and fluid
loss
- Disease prevented by proper cooking of
shellfish
- No vaccines are available
 Vibrio vulnificus
Structure : curved gram-negative facultative
anaerobe, fermenter, simple nutritional
requirements but requires salt for growth

Virulence :Antiphagocytic polysaccharide

capsule ( important for the ability to produce
severe, disseminated infections), cytolysins,
collagenase, protease, siderophores

Epidemiology : infection associated with

exposure of a wound to contaminated salt
water or ingestion of improperly prepared
shellfish.
 Vibrio vulnificus(Diseases)
primary septicemia after consumption of
contaminated raw oysters or rapidly progressive
wound infection after exposure to contaminated
seawater.

Wound infections: potentially fatal infections

characterized by fever , chills, erythema, pain, vesicles
or bullae formation , tissue necrosis, (mortality range
20%-30%)
Primary septicemia: sudden onset of fever, chills,
vomiting, diarrhea, abdominal pain. Secondary skin
lesions with tissue necrosis. Mortality rate 50%
Infections are most severe in patients with hepatic
disease, hematologic diseases, chronic renal failure
and those receiving immunosuppressive drugs
 Vibrio vulnificus
Diagnosis : culture of wound and
blood on TCBS

Tratment, prevention, and control:

- life-threatening illness that must be
promptly treated with antibiotics,
- Minocycline combined with
fluoroquinolone or cefotaxime is the
treatment of choice
- No vaccine is available
 Other vibrios

V.mimicus: diarrhea after ingestion of

uncooked seafood (raw oyster)
V.holisae: diarrhea
V.fluvialis : diarrhea
V.alginolyticus: eye, ear, wound
infections after exposure to seawater
V.damsela: wound infection
Aeromonadaceae
 Aeromonas
Are 1-4µm long and Motile species have
single polar flagellum (nonmotile species
apparently not associated with human
disease)

Facultatively anaerobic fermented rods.

21 species have been described

Produce large zones of hemolysis on blood

agar.

Virulence factors: endotoxin, hemolysins,

heat-labile and heat-stable enterotoxin
 Afimbriated Aeromonas
hydrophila

Nonadherent
Afimbriated
Bacterial Cells
and Buccal Cells
 Fimbriated Aeromonas
hydrophila

Adherent
Fimbriated
Bacterial Cells
and Buccal Cells
 Aeromonas
Grow on differential media used for
g(-) enteric rods and Their colony
morphology are similar to that of
them.

Are oxidase (+) and resistant to

O/129, not growth on media
containing 6% NaCl

A.hydrophila comlex ,A.caviae

complex , A.veronii biovar sobria
 Aeromonas (Diseses)
diarrheal disease (in otherwise healthy people) :
acute watery diarrhea, dysenteric diarrhea ( severe
abdominal pain, blood, leukocytes in the stool), chronic
illness with intermittent diarrhea.
Occur after ingestion of contaminated water or food
(fresh meat, diary products)
wound infections :opportunistic systemic disease
( immunocompromised patients, hepatobiliary disease
or underlying malignancy patients)
Occur after a traumatic injury associated with
exposure to contaminated water

Treatment: are resistant to penicillin, most

cephalosporins and erythromycins
Are susceptible to tetracycline, aminoglycosides, and
ciprpfloxacin
 Characteristics of Aeromonas and
Plesiomonas Gastroenteritis
Epidemiological
Features Aeromonas Plesiomonas
Natural Habitat Fresh or brackish water Fresh or brackish water
Source of Infection Contaminated water or food Contaminated water or food

Clinical Features

Diarrhea Present Present

Vomiting Present Present
Abdominal Cramps Present Present
Fever Absent Absent
Blood/WBCs in Stool Absent Present

Pathogenesis Enterotoxin (??) Invasiveness

 Plesiomonas
Is a g(-) rod with Multiple polar flagella (lophotrichous)

Is common in tropical and subtropical areas.

Is isolated from freshwater fish and many animals.
Most isolates are from stool cultures from patients
with diarrhea

Grows on differencial media used to isolate salmonella

and shigella from stool specimens.

Share antigens with S.sonnei and cross-reaction with

Shigella antisera occur

Is oxidase (+) ,DNase (+)

Plesiomonas shigelloides
Campylobacter
 Campylobacter
Comma shaped ,gram (-) rods,0.2-0.5μm wide ₓ 0.5-
5.0 μm
Motile by a polar flagellum
Most species microaerophilic
25 species and 11 subspecies
Different O antigens, heat-labile capsular and flagellar
antigens are used for epidemiological classification of
clinical isolates
C.jejuni : gastroenteritis
C.coli : gastroenteritis
C.upsalensis: gastroenteritis
C.fetus: systemic infections (bacteremia, septic
thrombophlebitis, arthritis, septic abortion, meningitis)
 Campylobacter jejuni
Structure :Thin ,gram (-) rods with comma , S or gull
wings shapes, motile with a single polar flagellum.

Culture: Charcoal or blood (remove toxic oxygen

radicals) with antibiotic added media is required
grows at 37-42°C in a microaerophilic conditions ( 5%-
7% oxygen) and 5%-10% CO2 on selective Skirrow`s
medium contains vancomycin ,polymyxin B , and
trimethoprim . Colonies are colorless to gray.

Growth characteristics : oxidase (+), catalase (+)

Small size of Campylobacter is used for recovering by
filtration of stool specimen ( 0.45 μm filter)
Do not oxidize or ferment carbohydrates

Antigenic structure : LPS , enterotoxins

 Campylobacter (Virulence)
cytotoxic enzymes , enterotoxins, adhesins are
detected
Factors that regulate adhesion, motility and invasion
into intestinal mucosa are poorly defined.

Guillain – Barre syndrome believed to be an

autoimmune disorder of the peripheral nervous
system characterized by development of symmetrical
weakness over several days and recovery requiring
months . caused by antigenic cross-reactivity between
oligosaccharides in bacterial capsule and
glycosphingolipids on surface of peripheral nerve
gangliosides
Reactive arthritis: immune-related late complication ;
painful joint swelling that may last for weeks to a year
 Campylobacter jejuni
Pathogenesis :
Is acquired by the oral from food, drink or contact
with infected animals and animal products.
Is susceptible to acids, 100-500 organisms is
need for infection.
Risk of disease is influenced by infectious dose.
Patient`s immune status affects the severity of
disease
Patients with hypogammaglobulinemia have
prolonged , severe disease
 Campylobacter jejuni(Pathogenesis)
Multiply in the small intestine, invade the
epithelium, produce inflammation.

Mucosal surface appears:

- ulcerated, edematous, bloody
- crypt abscesses in epithelial glands
- infiltration of the lamina propria with
neuthrophils, mononuclear cells, and
eosinophils
Campylobacterjejuni(Pathogenesis)
Gastrointestinal disease produces
histologic damage to the mucosal
surfaces of the jejunum, ileum, colon
Rarely , the bloodstream is invaded
(like enteric fever) (1.5/1000)
Role of cytopathic toxins, enterotoxins
and endotoxic activity have not been
defined
Are killed rapidly by complement and
antibody- mediated serum killing
 Campylobacter( epidemiology)

Zoonotic infection ; improperly prepared poultry

is a common source of human infections

Infections acquired by ingestion of contaminated

food (poultry), unpasteurized milk, or
contaminated water

person- to- person (fecal-oral) spread is unusual

Worldwide distribution, with enteric infections most

commonly seen in warm months.
Campylobacter (diseases)
 Campylobacter jejuni(diseases)
Acute enteritis with diarrhea, malaise, fever, and abdominal pain.
More than10 bowel movement per day , bloody stools
Most infections are self-limited but can persist for a week or more
Colitis, abdominal pain mimicking acute appedicitis, bacteremia
Chronic enteric infection develop in immunocompromised
patients (AIDS) and difficult to treat.
Extraintestinal infections are uncommon
Complications:
- C.jejuni ( serotype O:19)and C.upsalensis are associated with
Guillain-Barre syndrome(1/1000)
- reactive arthritis
Campylobacter jejuni(Diagnosis)
Specimens :stool

smears: typical “gull wing “shaped rod in

Gram strain ,Darkfield ,phase contrast
microscopy

Culture :requires use of selective media

( Skirrow ) or incubated in 5-10 CO2 (5-7%
O2 , microaerophilic condition) and 42 °C ;
requires incubation for 2 or more days.

Identification: catalase (+). Oxidase(+)

Campylobacter ( diagnosis )
Campylobacter jejuni(Diagnosis)

Antigen detection: immunoassay

detection of C.jejuni and C.coli
Sensitivity 80%-90% , specificity
>95%
Antibody detection: serologic testing
for IgM and IgG are useful for
epidemiological survays
 Campylobacter
( treatment, prevention ,and control)
Treatment : for gastroenteritis , infection is self-
limited and is managed by fluid and electrolyte
replacement
Serve gastroenteritis and septicemia are treated
with erythromycin, azithromycin (drugs of choice) ,
tetracycline, clindamycin, amoxiclave, imipenem, or
fluoroquinolones.
More strains are resistant to penicillin,
cephalosporins and sulfanamide

Prevention: Gastroenteritis is prevented by proper

preparation of food and consumption of pasteurized
milk; preventing contamination of water supplies
also controls infection.
 Campylobacter fetus
C.fetus is associated with septicemia and is
disseminated to multiple organs and causes diarrhea
(uncommon disease)

Spread from the gastrointestinal tract to the blood and

distal foci.

Spread is common in debilitated and

immunocompromised patients (liver disease, diabetes
mellitus, chronic alcoholism, malignancies)

S protein (heat-stable S layer) in C.fetus inhibits C3b

binding and subsequent complement and antibody
-mediated phagocytosis and killing (resistant to serum
killing)
 Campylobacter fetus
Diseases:
- intravascular infections
(septicemia, endocarditis, septic
thrombophlebitis)
- extraintestinal infections
(meningoencephalitis, abscesses)

Diagnosis: like C. jejuni, but cannot

grow at 42 C
 C.upsalensis
Catalase (-) or weakly (+).
Growths at 42C
Highly susceptible to drugs in selective media
(skirrow )
Filter method is suitable for isolation
Domestic pets and cats are reservoir
Opportunistic agent of infections in children
Present as acute enteritis with diarrhea , fever and
abdominal pain
Isolates from stool, blood , fetoplasental material of
human
Is associated with Guillain-Barre syndrome
Arcobacter
 Arcobacter
The genus Arcobacter which is related to Campylobacter was
introduced in 1991.
Nevertheless, unlike Campylobacter, Arcobacter spp. are
aerotolerant and their optimal growth temperature is at 30oC.
Members of this genus inhabit very diverse environments
Distinguishing from Campylobacter:
- Hydrolysis of indoxyl acetate
- growth at 15-36 C ,but not at 42C
- Inability to hydrolyze hippurate
• separated to 5 major groups:
A.cryaerophilus (2 subgroups)
A.nitrofigilis
A.butzleri
A.skirrowii
A. halophilus
 Arcobacter
A.cryaerophilus: grows well under aerobic
conditions. May require microaerophilic conditions
for initial isolation
Optimal growth at 30 C
Resemble C.fetus but is Indoxyl acetate (+)
Sensitive to nalidixic acid, resistant to cephalothin
Growth in CIN agar is better than Skirrow
A. cryaerophilus has been found both in
association with diseased as well as healthy
humans and animals caused that these bacteria
were considered to play a role as food borne or
waterborne agents
 Arcobacter
A.nitrofigilis:
a nitrogen fixing bacterium
a cryophilic species
Grows optimally at 25C
Urea (+)
Non pathogenic for human

A. skirrowii:
isolates from fluids of bulls, aborted fetuses and
diarrheal feces from cows , pigs and sheep.
 Arcobacter
A.butzleri: aerotolerant both at 30C and
36C ( separatation from A. cryaerophilus
)
Grows on MacConkey and glycine and
nitrate containing media and in 1.5% and
3.5% NaCl
Isolated from stools of patients with
diarrheal illness.
Rarely isolates from abdominal
contents , peritoneal fluid and blood
Helicobacter
 Helicobacter
First isolated by Marshal and Warren in1983
Spiral , G(-) rods resembling campylobacter
(0.5-1.0μm wide*2-4 μm long) , coccoid form in
older cultures
Motile (polar flagella)
catalase and oxidase (+)
- 30 species are characterized according to:
sequence analysis of their 16S rRNA genes
cellular fatty acid , (different from
Campylobacter with high % of O:14 and low
O:16 and presence of O:18-OH-3)
presence of polar flagella
 Helicobacter ( diseases)
H.pylori : (gastric)
Gastritis , peptic ulcer, gastric adenocarcinoma,
gastric mucosa-associated lymphoid tissue (MALT)
B-cell lymphomas
H.cinaedi: enterohepatic (isolated from homosexual
men with HIV)
Gastroenteritis, septicemia, proctocolitis, cellulitis
H.fennelliae : enterohepatic(isolated from
homosexual men with HIV)
Gastroenteritis, septicemia, proctocolitis
Helicobacter species flexispira taxon 8:
bactermia with cellulitis in immunocompromised
patients
H.canadensis : Gastroenteritis
H.canis:Gastroenteritis
H.pullorum:Gastroenteritis
 Helicobacter pylori
Morphology : Curved, gram- negative rods ,
motile by multiple flagella at one pole
Lipid A has low endotoxin activity compared
with other (-) bacteria
O side chain is antigenically similar to Lewis
blood group antigens, which may protect the
bacteria from immune clearance
 H.pylori
Culture: require complex medium
supplemented with 5% defibrinated horse
or sheep blood, serum, charcoal, starch,
egg yolk( Brucella agar ,BHI,or TSB
mediums with supplements and
antibiotics ) .
Microaerophilic conditions( 10% CO2, 5%
O2 and 85% N2 or 10%CO2 with air ).
Grows in 3-6 days at 37°C in a
microaerophilic environment in Skirrow`s
medium with vancomycin, polymyxin B
and trimethoprim ; and in chocolate
medium
 H.pylori
Growth characteristics : oxidase- positive ,
catalase-positive, do not ferment or
oxidase carbohydrates, metabolize amino
acids by fermentative pathways

-Urease production at very high levels is

typical of gastric helicobacters, and
uncommon in intestinal helicobacters

- Flagella and urease are important for

survival in gastric acids and rapid
movement through the viscous mucus
layer towards a natural pH environment
H.pylori ( Virulence factors)
 H.pylori (pathogenesis)
Virulence factors:
A-Initial colonization of H.pylori facilitate by:
1- blockage of acid production by acid inhibitory
protein
2- Urease activity ;
- neutralization of gastric acids by production of
the ammonia
- stimulate monocytes and neuthrophils
chemotaxis
- stimulate production of inflammatory cytokines
- stimulate production of high amount of gastrin
and acid
 H.pylori (pathogenesis)
B- H.pylori can pass through the gastric mucus by
actively motility of flagella

C- adhere to the gastric epithelial cells by multiple

surface-adhesion proteins
- haemagglutinins ; binding to N-acetyl-noraminil-
lactose
- sialic acid- binding adhesin
- pili; adhere to phosphatidyl-ethanol amin and
laminin
- Lewis blood group adhesin; may protect the
bacteria from immune clearance
 Surface proteins can also bind host proteins and
help the bacteria evade immune detection.
 H.pylori (pathogenesis)
D- Localized tissue damage is mediated by:
1- Urease byproducts
2-Mucinase; disrupts gastric mucus
3-Phospholipases; C,A1,A2 ; disrupts gastric
mucus
4-Vacuolating cytotoxin A (VacA); after
endocytosis by epithelial cells, damage the
cells by producing vacuoles
- 60% of H.pylori strains produces Vac A
but toxin production is not seen in strains of
Patient with long time non-ulcerative gastritis
 H.pylori (pathogenesis)
E- Cag A protein ; interferes with the normal
cytoskeletal structure of the epithelial cells
- an important virulence factor of H.pylori is the
Cytotoxin-associated gene (cagA) that resides on
a pathogenicity island containing approximately 30
genes.
- These genes encode a structural (type IV
secretion system) that acts like a syringe to inject
the Cag A protein into the host epithelia cell
The cag PAI (phosphoribosylanthranilate
isomerase) genes also induce IL-8 production,
which attracts neutrophils.
Release of proteases and reactive oxygen
molecules by the neuthrophils is believed to
contribute to gastritis and gastric ulcers
 H.pylori (pathogenesis)
F- Superoxide dismutase; prevent
phagocyting killing by neutralizing
oxygen metabolites
Catalase; prevent phagocyting killing
by neutralizing oxygen peroxides
Heat- shock proteins; enhances
expression of urease
 H.pylori (pathogenesis)
Long life colonization in the antrum of stomach
of untreated humans
Grows at pH = 6-7
Gastric mucus is impermeable to acid and has
a buffering capacity.
On the lumen side of the mucus pH is low (1-
2) ;on the epithelial side pH is about 7.4
H.pylori produces a protease
urease activity produces ammonia
TNF-α, IL-6 and IL-8 , urease activity and
cytokines are caused Chronic inflammation of
stomach
 H.pylori (pathogenesis)

H.pylori infection (weeks to months)

chronic superficial gastritis ( years to
decades )
- peptic ulcer disease; chronic
- superficial gastritis;
- chronic atrophic gastritis gastric
adenocarcinoma
 H.pylori ( epidemiology)
Infections are common, particularly in people in a low
socioeconomic class or in developing nations (70%-90%)

Humans are the primary reservoir; Incidence of carriage in

developing nations (70%-90%) most before age 10 years.

Person-to-person spread is important (typically fecal-oral)

is worldwide with no seasonal incidence of disease

70%-100% of patients with gastritis, gastric ulcer, duodenal

ulcers are infected with H.pylori

Colonization with H.pylori appears to offer protection from

gastroesophagal reflux disease and adenocarcinoma of
the lower esophagus and gastric cardia
 Diseases
Gastritis ; infiltration of neutrophils and
mononuclear cells in to gastric mucosa.
Acute phase: feeling of fullness; nausea;
vomiting; hypochlorhydria ( decreased
acid production );
Chronic phase: disease confined to the
gastric antrum in individuals with normal
acid secretion, or involve the entire
stomach (pangastritis) if acid secretion is
suppressed.
 Diseases
Peptic ulcer (10-15%) in chronic gastritis.
Developing to gastric ulcer (isolate 85%) or
duodenal ulcer(isolate 95%)
Gastric cancer; replacement of normal
gastric mucosa with fibrosis and
proliferation of the epithelium in chronic
gastritis. (high risk for cancer is associated
with cagA positive strains and high levels
of IL-1 production)
MALT lymphoma; monoclonal population of
B cells
 H.pylori(Diagnosis)
Microscopy : Histological examination of
biopsy specimen is sensitive and specific;
hematoxylin-eosin stain, Gram stain Warthin-
Starry silver stain( 100% sensitivity and
specificity)

Urease test: relatively sensitive and highly

specific; urea breath test is a noninvasive test
(detection in 1-2 hours with sen. 75-95%and
spe. 100%)
Noninvasive urease testing of human breath:
C13 or C14 labeled urea solution ( excellent
spe. and sen.)
 H.pylori(Diagnosis)
H.pylori antigen test : polyclonal and
monoclonal immunoassays for
H.pylori antigens; performs with stool
specimens; sensitive and specific
95%;

Serology: useful for demonstrating

exposure to H.pylori .IgM disappears
rapidly. IgA and IgG persist for
months to years
 H.pylori(Diagnosis)
Culture : requires incubation in
microaerophilic condition ; chocolate agar
(nonspecific medium) and modified
Skirrow medium (specific medium) are
required ; growth is slow (up to 2 weeks) ;
relatively insensitive unless multiple
biopsies are cultured
Identification; microscopic morphology,
oxidase , catalase, urease

Nucleic-Acid based amplification tests:

PCR based tests are restricted to
research labs and not in clinical use
.
 H.pylori ( treatment)
Treatment : multiple regimens have been evaluated for
treatment of H.pylori infections.

Combined therapy with tetracycline, metronidazole,

bismuth, and omperazole for 2 weeks has had high
success rate
Omperasole + a macrolide (clarithromycin ) a beta-
lactam(amoxicillin) for 7-10 days .
resistance to clarithromycin and metronidasole is
important.( susceptibility testing is recommended)

Prophylactic treatment of colonized individuals has not

been useful and potentially has adverse effects, such
as predisposing patients to adenocarcinomas of the
lower esophagus
 prevention and control
Human vaccines are not currently
available
Use of H.pylori antigens in experimental
vaccines that stimulate TH1 cells leads
to enhanced inflammation
Use of antigens in combination with
mucosal adjuvants that induce aTH2
cell response is protective in an animal
model
 Other Helicobacters ( diseases)
H.cinaedi: enterohepatic (isolated from
homosexual men with HIV)
Gastroenteritis, septicemia, proctocolitis,
cellulitis
H.fennelliae : enterohepatic (isolated from
homosexual men with HIV)
Gastroenteritis, septicemia, proctocolitis
Helicobacter species flexispira taxon 8:
bactermia with cellulitis in immunocompromised
patients
H.canadensis : Gastroenteritis
H.canis: Gastroenteritis
H.pullorum: Gastroenteritis