1. Erysipelothrix rhusiopathiae

2. Listeria monocytogenes Small, Gram +, nonsporing rodSmall, Gram +, nonsporing rod End-over-end tumbling motility when grown at 20-25°C, not at 37°CEnd-over-end tumbling motility when grown at 20-25°C, not at 37°C Facultative anaerobeFacultative anaerobe Isolated from soil, water, effluents, foods, humans/animal fecesIsolated from soil, water, effluents, foods, humans/animal feces Ruminants maintain Listeria spp in rural environment via continuous fecal-oral enrichmentRuminants maintain Listeria spp in rural environment via continuous fecal-oral enrichment

3. Six Species of Listeria L. monocytogenes – – potentially pathogenic, cause listeriosis – –humans, other vertebrates, domestic, wild birds, mammals L. ivanovii – –rare human disease – –common in abortions, stillbirths, neonatal septicemias: sheep, cattle L. seeligeri: avirulent, but implicated in one case of human listeriosis L. seeligeri, L. innocua, L. welshimeri, L. grayi: avirulent, saprophytes

4. Listeriosis Humans, domestic animalsHumans, domestic animals –described in ≥ 40 species of animals –usually follows ingestion –outbreaks, sporadic cases related to food –asymptomatic fecal carriage common, especially for those in contact with domestic animals –Incidence increases in summer, when outbreaks of food-borne disease are more common.

5. Listeriosis - Monogastrics Entry via GI tract, ~ 20 h incubation periodEntry via GI tract, ~ 20 h incubation period Relatively high infectious dose (~ 10 6 CFU)Relatively high infectious dose (~ 10 6 CFU) usually asymptomatic/mild, influenza-like symptoms in adult humansusually asymptomatic/mild, influenza-like symptoms in adult humans –more serious infection immunocompromised –CNS infections (encephalitis, meningitis), fatal bacteremia –puerperal sepsis –crosses placenta => in utero fetal infection stillbirths, preterm laborstillbirths, preterm labor infant born with systemic infectioninfant born with systemic infection

6. Listeriosis - Monogastrics two forms of neonatal meningeal sepsistwo forms of neonatal meningeal sepsis –early-onset, predominantly septicemia: low birth weight, obstetrical complications, genital tract colonization –late onset, meningitis: normal birth weight; obstetrical complications, colonization of genital tract infrequent outside neonatal period, incidence increases with advancing ageoutside neonatal period, incidence increases with advancing age overall: 5th most common cause of bacterial meningitis in the USoverall: 5th most common cause of bacterial meningitis in the US 2nd in neonates, individuals over 602nd in neonates, individuals over 60

7. Listeriosis - Ruminants meningoencephalitismeningoencephalitis most common form = circling disease (small ruminants)most common form = circling disease (small ruminants) –animal circles in one direction only –unilateral facial paralysis, difficulty in swallowing –fever, blindness, headpressing –paralysis, death in 2 - 3 days

8. Listeriosis - Ruminants –in pregnant animals, may localize in placentomes cross-over to amniotic fluid, multipliescross-over to amniotic fluid, multiplies ingested by fetus, causes fetal death, abortioningested by fetus, causes fetal death, abortion –in milking cows, mammary gland can be involved subclinical mastitis, contamination of milksubclinical mastitis, contamination of milk may survive low temp pasteurization inside MØmay survive low temp pasteurization inside MØ lengthy survival in naturelengthy survival in nature growth at low temperaturesgrowth at low temperatures –entry also by nasal mucosa, conjunctivae –direct access to nervous system via dental plates of trigeminal ganglia

9. Virulence Factors and Pathogenesis - Adherence and Invasion Uptake: induced phagocytosisUptake: induced phagocytosis –InlA, InlB (internalin): stimulates phagocytosis

10. After epithelial cell entryAfter epithelial cell entry –escapes phagosome, multiplies in cytoplasm –exocytosis from epithelial cell followed by phagocytosis by MØ, PMN –multiplication followed by death of phagocytes, secondary phagocytosis –systemic spread

11. Virulence Factors and Pathogenesis - Listeriolysin Major virulence factor: listeriolysinMajor virulence factor: listeriolysin –thiol-activated cytolysin, hemolysin –mediates escape from phagocytic vesicle –40-50% amino acid sequence similarity to other thiol-activated toxins (eg, streptolysin O) LLO mutants: LD 50 5 logs higher than WT, do not survive in MØLLO mutants: LD 50 5 logs higher than WT, do not survive in MØ B. subtilis expressing LLO escapes vesicle, enters cytoplasm of macrophagesB. subtilis expressing LLO escapes vesicle, enters cytoplasm of macrophages

12. Actin-based Motility Polymerize actin, form tailsPolymerize actin, form tails –move through cytoplasm –invade adjacent cells –depolymerized as organism moves –secreted actin nucleating factor: ActA –localized at one end of the bacterium

13. Virulence Factors and Pathogenesis Bacteria encountering plasma membrane continue to move forwardBacteria encountering plasma membrane continue to move forward –produce protrusions extending into adjacent cell: listeriopods –escape listeriopod in double- membrane vesicle, enter cytoplasm of adjacent cell Cell-cell spread mediated in part by PLCsCell-cell spread mediated in part by PLCs