Yersinia Virulence Factors

Yersinia Virulence Factors

• Type 3 secretion system (T3SS) is found in all pathogenic Yersinia.
• Y.pestis has acquired additional plasmid DNA that enables: • Colonization and transmission via the flea vector • Survival in blood • Lost motility and cell adhesive properties to enable colonization of mammalian host

Enterobactericeae: Common Aspects

• Optimum temperature: 37°C
• Gram-negative, non-spore forming rods
• Facultative anaerobes
• Catalase positive, oxidase negative, nitrate reductase positive
• G+C content: 38-60%, genome size: ~5 Mbp
• Motile via peritrichous flagella (a few exceptions)
• Habitats: gastrointestinal tract of hosts, including humans, animals, and insects
• Widespread contamination of environment: sewage, soil, water, plants, and food
• Routes of infection: oral, via wounds, urinary tract, and respiratory tract
• Disease patterns: diarrhea, sepsis, urinary tract, CNS, and brain

Genus Salmonella

• Classification of Salmonella species is complex
• 2 species, 7 subspecies, and >2,600 serovars
• Some serovars are host-restricted (e.g., Typhi, human; Abortusovis, sheep)
• Most serovars infect a wide range of hosts (e.g., Typhimurium)

Genus Salmonella: General Characteristics

• Non-lactose fermenter (E. coli ferments lactose, but Shigella does not)
• Indole test negative (E. coli positive, Shigella variable)
• Various selective media can distinguish Salmonella from E. coli/Shigella by: • H2S production • Acid production during carbohydrate fermentation • XLD media, SS media

Typhoidal Salmonella: Impact and Disease

• Typhoid fever (S. Typhi): ~15 million new cases each year, with about 1% deaths
• 1st phase: slow fever, rose spots, mild, bacteremia
• 2nd phase: organism reaches gallbladder, formation of ulcers, hemorrhage, death (20%)
• Typhoid state: “muttering delirium” or “coma vigil” (picking at bedclothes and imaginary objects)

Non-Typhoid Salmonella (NTS): Impact

• Global burden: ~94 million cases (155,000 deaths) each year, of which about 80 million were estimated as foodborne origin
• UK data: 8-9,000 confirmed cases per year
• Predominant serovars: Salmonella Enteritidis, Salmonella Typhimurium, Salmonella Heidelberg, Salmonella Newport
• NTS causes self-limiting enteritis in healthy individuals
• Can be invasive (iNTS) in regions with immunocompromised/malnourished individuals (e.g., in sub-Saharan Africa)

Mechanism of UPEC Infection

• Intestine of healthy individuals contains UPEC
• Periurethral contamination with UPEC can occur after a bowel movement or be propelled into the bladder during sexual intercourse
• For infection, P fimbriae must bind to the P blood group antigen, which is found in 99% of people (D-galactose-D-galactose)

Yersinia

• Yersinia use M cells to enter the host but remain extracellular on macrophages
• Despite different routes of host entry, all pathogenic Yersinia cross the epithelial barrier
• Yersinia does this via M (microfold) cells, specialized epithelial cells of mucosal-associated lymphoid tissue (MALT)
• Yersinia quickly traffics to lymph nodes or tissues and establishes itself
• Yersinia spreads systematically by accessing the bloodstream and colonizing deep tissue sites, such as liver and spleen

Yersinia Virulence Factors

• Type 3 secretion system (T3SS) is found in all pathogenic Yersinia.
• Y.pestis has acquired additional plasmid DNA that enables colonization and transmission via the flea vector and survival in blood, but has lost motility and cell adhesive properties.

Salmonella

Typhoidal Salmonella

• Typhoid fever (S.Typhi) affects ~15 million people each year, with a 1% death rate.
• The disease has two phases:
  • 1st phase: slow fever, rose spots, mild, bacteremia.
  • 2nd phase: organism reaches gallbladder, formation of ulcers, hemorrhage, death (20%).
• Typhoid state is characterized by "muttering delirium" or "coma vigil" (picking at bedclothes and imaginary objects).
• Enteric fever (S.Paratyphi) is similar to typhoid fever but less severe and rare.

Non-Typhoidal Salmonella (NTS)

• Global burden: ~94 million cases (155,000 deaths) each year, with ~80 million cases being foodborne.
• UK data: 8-9,000 confirmed cases per year.
• Predominant serovars: S.Enteritidis, S.Typhimurium, S.Heidelberg, and S.Newport.
• NTS causes self-limiting enteritis in healthy individuals, but can be invasive (iNTS) in regions with immunocompromised/malnourished individuals, e.g., in sub-Saharan Africa.

E. coli (MNEC)

• Affects 1 in every 2,000-4,000 infants.
• Major cause of CNS infections in infants <1 month old.
• Primary bloodstream infection with secondary distribution to the CNS is the mechanistic basis of infection.
• 80% of E. coli strains involved synthesize K-1 capsular antigens, which is a major virulence factor.

Intestinal Pathogenic E. coli

• Common cause of gastrointestinal infections (1 in 5 people affected each year in the UK).
• Transmitted by infected food and water (or via person-to-person).
• Symptoms vary depending on pathotype:
  • Mild watery diarrhea: typically ETEC.
  • Dysentery: typically EIEC.
  • Severe bloody diarrhea: typically EHEC.
  • Persistent diarrhea: typically EPEC, EAggEC.
  • Vomiting, abdominal pain, fever: all; haemolytic uraemic syndrome (HUS): only EHEC.

Genus Shigella

• 4 Shigella species based on serological typing:
  • A: S.dysenteriae (most severe, ancient cause of epidemics).
  • B: S.flexneri (most frequent, 60% cases in developed world).
  • C: S.boydii (confined to the Indian sub-continent).
  • D: S.sonnei (mildest infection, developed world).
• Phylogenetic typing (16S rRNA) shows that Shigella spp. and E. coli are closely related.

Shigella Virulence Factors

• Plasmid-borne factors (pINV):
  • Entry region: codes for type 3 secretion system (T3SS), which allows the bacterium to inject proteins directly into the host cell.
  • T3SS is pivotal to infection.
• Chromosomal factors:
  • SHI-1: enterotoxins (SigA, Pic, Set1A,1bB).
  • SHI-2: siderophores (IucA-D, IutA).
  • SHI-3: siderophores (IucA-D, IutA).
  • SHI-O: serotype conversion/O-antigen.
  • Stx-phage p27: shiga toxin.

Order: Enterobacterales

• General morphological and biochemical characteristics:

  • Emended family Enterobacteriaceae.
  • 29 genera, including the type genus Escherichia.
  • Optimum temperature: 37°C.
  • Gram-negative, non-spore forming rods.
  • Facultative anaerobes.
  • Catalase positive.
  • Oxidase negative.
  • Nitrate reductase positive.
  • G+C content: 38-60%.
  • Genome size: ~5 Mbp.
  • Motile, via peritrichous flagella (a few exceptions).

• Family Yersiniaceae:

  • 7 genera, including the type genus Yersinia.
  • Optimum temperature: 28-29°C.
  • Some lack nitrate reductase.
  • G+C content: ~47%.
  • Genome size: 4.6 Mbp.
  • Non-motile at 37°C (with all but Y.pseudotuberculosis).