Virulence Factors for Gastrointestinal Pathogens*

Organism

Virulence factor

How it promotes virulence.

Dental Caries

Streptococcus mutans and 
Streptococcus sobrinus, Lactobacillus casei, 
Actinomyces sp., 
Bifidobacterium sp., and low-pH tolerant Streptococcus sp.

1. Adhesins
2. Acidogenicity- sucrose to lactic acid
3. Aciduricity
4. EPS
5. Intracellular polysaccharides

1. Bind to surface of tooth
2. rapid uptake and fermentation of carbohydrates to lactic acid/acidic byproducts
3. the ability to tolerate, grow, and continue to make acid in acidic  environments
4. synthesis of extracellular polymers or EPS from sucrose to consolidate attachment of the plaque to the surface of the tooth
5. production of intracellular polysaccharides during periods of excess carbohydrate availability which can be converted to acid during times when carbohydrates are not available.

Periodontal disease (gingivitis and periodontitia)

Polymicrobial

Adhesins, hemolysins, proteases, collagenases

Bind to surface of tooth, hemolysins and proteases cause damage of gingiva

Stomatitis

HSV

Latency in host tissues

Allows lifelong infection, sporadic viral shedding and recurrences of viral infection.

Stomatitis

Candida albicans

Biofilm formation, germ tube formation

Imbalance of host microbiota resulting in overgrowth of Candida, allows organism to penetrate host tissues

Mumps

Mumps virus

The hemagglutinin-neuraminidase on the Mumps virus binds to a trisaccharide containing an α2,3-linked sialic acid on host cells

Tropisms for glandular tissue and tissues of the CNS

Peptic ulcer disease

Helicobacter pylori

1. pH sensing
2. produce flagella,
3. urease,
4. Vac A (vacuolating toxin)
5. Cag A

1. Ability to sense pH triggers organism to make urease
2. Flagella help bacteria get through the mucus that covers the host cells of the stomach/duodenum
3. urease produces ammonium ions, which buffer the gastric acid.
4. The Vac A protein causes vacuoles to form in certain cells and produces pores in human cells.
5. The Cag A protein is injected in host cells by the bacteria, which causes several changes in host cell signaling

Food poisoning

Staphylococcus aureus

8 enterotoxins; heat stable

Cause serotonin release in the intestine, which then binds to 5-hydroxytryptamine receptors on vagal afferent neurons and causes emesis.

Food poisoning; B. cereus type I

Bacillus cereus; emesis

Heat-stable enterotoxin depsipeptide cereulide

Nausea and vomiting is believed to be caused by cereulide's binding to and activation of 5-HT3 receptors (5-hydroxytryptamine, or serotonin receptors) that increase afferent vagus nerve stimulation.

Food poisoning; B. cereus type II

Bacillus cereus; diarrhea

Heat-labile enterotoxins hemolysin BL (HBL) and nonhemolytic enterotoxin

Enterotoxins adenyl cyclase-cyclic adenosine monophosphate system in intestinal epithelial cells and causing fluid accumulation in the lumen of the intestine.

Food poisoning

Clostridium perfringens

Enterotoxin

Enterotoxin binds to the brush-border membrane in the intestine and disrupts ion transport, altering membrane permeability. Excess amounts of ions and water enter the lumen, resulting in a watery diarrhea.

Noninflammatory viral gastroenteritis

Rotavirus, adenovirus, Coronavirus (SARS CoV-2) and Caliciviruses (Noroviruses and Sapoviruses)

Noroviruses- bind to the histocompatibility blood group antigens expressed on epithelial cells.

SARS CoV-2 binds to ACE-2 (angiotensin converting enzyme-2) on the surface of epithelial cells.

Rotavirus infect cells in the villi of the small intestine causing shortening and blunting of the microvilli. The Rotavirus multiplies in the cells cytoplasm and damages the host cell’s transport systems. One viral protein NSP4 is a viral enterotoxin that induces fluid secretion via a calcium dependent signal transduction pathway.
Adenovirus infects epithelial cells of the intestine.

Invade and destroy mature epithelial cells in the middle and upper villus, causing decreased absorption of sodium and water from the bowel lumen.

Noninflammatory bacterial gastroenteritis

ETEC

Two enterotoxins called LT (heat labile toxin) and ST (heat stable toxin)

Both toxins ultimately stimulate the secretion of chloride by the host cells, which results in a watery diarrhea

Noninflammatory bacterial gastroenteritis

EAEC

aggregative adherence fimbriae I (AAFI), enteroaggregative heat stable toxin, plasmid encoded toxin

AAFI allows EAEC to adhere to the intestinal mucosa which enhances mucus production by the host cells. The mucus then encases the bacteria in a biofilm on the surface of the intestinal mucosa, and production of toxins follows.
Both toxins induce fluid secretion and the prolonged watery diarrhea associated with this infection.

Noninflammatory bacterial gastroenteritis

EPEC

Makes NO toxin

attaching-and-effacing histopathology in the small intestine

Noninflammatory bacterial gastroenteritis

Vibrio parahemolyticus

Thermostable hemolysin (Kanagawa hemolysin)

The hemolysin induces chloride ion secretion in epithelial cells by increasing intracellular calcium levels

Noninflammatory bacterial gastroenteritis; Cholera

Vibrio cholerae

Enterotoxin known as cholera toxin

An A-B toxin; On exposure to small bowel epithelial cells, each B subunit rapidly binds to GM1 monosialoganglioside. The A moiety migrates through the epithelial cell membrane and catalyzes the transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD) to a GTP-binding protein that regulates adenylate cyclase activity. The ADP-ribosylation of GTP-binding protein inhibits the GTP turnoff reaction and causes a sustained increase in adenylate cyclase activity. The resultant increased intracellular cyclic AMP acts at two sites to cause net secretion of isotonic liquid within the small bowel lumen. First, the increased cyclic AMP inhibits sodium chloride absorption across the glycocalyx via the cotransport mechanism; and second, the increase in cyclic AMP stimulates active chloride secretion into the gut lumen. Water in the tissues follows the ions, causing the profuse watery diarrhea.

Parasitic gastroenteritis

Giardia lamblia

Flagella, taglin (trypsin-induced Giardia lectin), GLAM-1 (Giardia lamblia adherence molecule- 1), adhesive disk, and parasite induced disaccharidase deficiency, cyst

Flagella help trophozoite make contact with enterocytes. Taglin and GLAM-1 help the trophozoite to bind to the enterocyte. The adhesive disk helps the trophozoite remain on the surface of the enterocyte. Inflammation and certain factors produced by the parasite causes a disaccharidase deficiency in the small intestine. The epithelial cells lining the microvilli do not absorb ingested disaccharides, causing an osmotic diarrhea with bloating, flatulence, and watery diarrhea. The cyst keeps the parasite alive in the environment outside the host’s intestines.

Pseudomenbranous colitis

Clostridioides difficile

Toxins A and B

Toxin A disrupting intercellular tight junctions.  Toxin B disrupts intestinal cell cytoskeletons through actin depolymerization.

Inflammatory Bacterial dysentery

Campylobacter jejuni

Shiga toxin

interrupts protein synthesis by removing an adenine residue from the 28S rRNA in the 60S ribosomal unit

Inflammatory Bacterial dysentery

Shigella sp.

Shiga toxin

See above

Inflammatory Bacterial dysentery

EHEC

Shiga toxin

See above

Inflammatory Parasitic dysentery

Entamoeba histolytica

Trogocytosis, cyst

E. histolytica ‘nibbles’ sections of human cell membrane, trogocytosis. The amoeba then recycles and presents the human cell’s membrane proteins to disguise itself from the immune system. The cyst keeps the parasite alive in the environment outside the host’s intestines.