Listeria spp.

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Listeria spp.
L. monocytogenes L. ivanovii L. murrayi L.
grayi L. seeligeri L. innocua L. welshimeri
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Listeria spp.

• ?????? ????? ????? (???? um 0.5-2.0 ) ???
  ???????.

• ???? ?????? ?????, ???? ????? ?????.
• ??????? ??????????, ?????? ??? ?- 10 CO2
• ????? 20-400 motility
• ?????? 4-450 pH 5 - 9.6
• ??? ???????, ???? ?????

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????????????? 5 ????? , ?? 2 ?????? ????"?

• ????? ????? ??????
• L. monocytogenes ???"? ?????? septicemia
  (??????,????? ???? ???) ????? ?????
  ??? ????

???, ????, ??? ???? ???? ????
??????? " " " " ???? L.
ivanovii ??? ???? ????
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?????? ?????????

• 13 ?????? ????????? ???????? ?? ???????? ???????
  ??? ????????.
• ???? ?? ??????? ??????? ????????? ????? ???????
  1/2a, 1/2b, 4b

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Camp test

• Rhodococcus equi Staph. aureus
• L. Monocytogenes -
• L. Ivanovii -

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• ??? ???
• ????? ?????? -"??????? ?????"
• ????? ??? ??? ????? ?????, ?????? ???
• ????? ???? ???.

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????????? encephalitis
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????? ??????

• listeriolysin O (haemolysin) LLO- ????? ??????
  ????? ????? ????? ??????? ?? ???????
• ?????? ????? ??????? ?????? ??? (surface
  proteins) internalin
• InlA ?- InlB ?? ??????? ??????

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• ??? stress -
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• ?????? ??????????? ???? ?????
• ?????? ????? ????? ?????
• ?????? ??????? ????? ??? ????

• ????? ??? ?????? ??????
• ???? ? C.N.S.
• ????? -?????? ???? ?? perivascular cuffing

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zipper mechanism

• zippering of the host cell membrane around the
  bacterium as it enters.
• This mode of entry into non-professional
  phagocytes is employed by Yersinia
  pseudotuberculosis and Listeria monocytogenes.
• Bacterial ligand interacts with a surface
  molecule on the host cell.
• The receptor is generally a protein involved in
  cell adhesion and/or activation of the
  cytoskeleton machinery.
• The ligand-receptor interaction induces local
  rearrangements in actin cytoskeleton and other
  signals that culminate in the tight envelopment
  of the bacterial body by the plasma membrane.

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• L. monocytogenes infects both human and aminals
  causing meningitis, sepsis, and abortion, 
• L.ivanovii is restricted to sheep and cattle, in
  which it causes septicemic disease, neonatal
  sepsis and abortion, but no brain infection.
• The other species are generally considered
  nonpathogenic

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Schema of intracellular life cycle of
pathogenic Listeria
Reproduced from Vazquez-Boland JA, et al., 2001.
Pathogenicity islands and virulence evolution
inListeria. Microbes Infect. 3(7)571-584.
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Virulence Factors

• InvasionAuto InlA InlB LpeA p60
• Peptidase Lsp
• Regulation PrfA
• Stress protein ClpC ClpE ClpP
• Toxin LLO LLS

• Actin-based motility ActA
• Adherence Ami FbpA
• Bile resistance BSH
• Exoenzyme Mpl PlcA PlcB SMase (L. ivanovii)
• Intracellular growth Hpt LplA1 SvpA

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Virulence Factors Actin-based motility

• ActA Factor responsible for actin-based motility
  and cell-to-cell spread

Listeria
 Domains of ActA and model of Listeria actin tail
assembly (Reproduced from Goldberg MB, 2001.
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Virulence Factors

• InvasionAuto InlA InlB LpeA p60
• Peptidase Lsp
• Regulation PrfA
• Stress protein ClpC ClpE ClpP
• Toxin LLO LLS

• Actin-based motility ActA
• Adherence Ami FbpA
• Bile resistance BSH
• Exoenzyme Mpl PlcA PlcB SMase (L. ivanovii)
• Intracellular growth Hpt LplA1 SvpA

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Virulence Factors Adherence

• Ami plays a role in the adhesion of L.
  monocytogenes to eukaryotic cells via its cell
  wall-binding domain.
• FbpA A fibronectin-binding protein present on
  the listerial surface that can mediate adherence
  to host cells but also act like a chaperone for
  two virulence factors, LLO and InlB

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Virulence Factors

• InvasionAuto InlA InlB LpeA p60
• Peptidase Lsp
• Regulation PrfA
• Stress protein ClpC ClpE ClpP
• Toxin LLO LLS

• Actin-based motility ActA
• Adherence Ami FbpA
• Bile resistance BSH
• Exoenzyme Mpl PlcA PlcB SMase (L. ivanovii)
• Intracellular growth Hpt LplA1 SvpA

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Virulence Factors

• InvasionAuto InlA InlB LpeA p60
• Peptidase Lsp
• Regulation PrfA
• Stress protein ClpC ClpE ClpP
• Toxin LLO LLS

• Actin-based motility ActA
• Adherence Ami FbpA
• Bile resistance BSH
• Exoenzyme Mpl PlcA PlcB SMase (L. ivanovii)
• Intracellular growth Hpt LplA1 SvpA

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Virulence FactorsIntracellular growth

• Hpt (Hexose phosphate transporter) The mammalian
  G6PT is responsible for the uptake of G6P from
  the cytosol into the endoplasmic reticulum for
  its conversion into glucose.
• Hpt mimics the function of the mammalian G6PT to
  steal fueling metabolites from host cell cytosol
  for the benefit of the microbe.
• vpA (surface-virulence associated protein)  A
  novel factor may be involved in promoting
  bacterial escape from phagosomes of bacteria

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Virulence Factors

• InvasionAuto InlA InlB LpeA p60
• Peptidase Lsp
• Regulation PrfA
• Stress protein ClpC ClpE ClpP
• Toxin LLO LLS

• Actin-based motility ActA
• Adherence Ami FbpA
• Bile resistance BSH
• Exoenzyme Mpl PlcA PlcB SMase (L. ivanovii)
• Intracellular growth Hpt LplA1 SvpA

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Virulence FactorsInvasion

• Auto  surface protein in L. monocytogenes but
  absent in L. innocua  Required for entry of L.
  monocytogenes into nonphagocytic cells and
  necessary for full virulence
• InlA (Internalin), InlB Promote entry into
  host cells.  Mediate the crossing of the
  intestinal and placental barriers, and invasion
  of the central nervous system (CNS) may also be
  mediated by the interaction between InlA and
  E-cadherin.

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Virulence Factors

• InvasionAuto InlA InlB LpeA p60
• Peptidase Lsp
• RegulationPrfA
• Stress protein ClpC ClpE ClpP
• Toxin LLO LLS

• Actin-based motility ActA
• Adherence Ami FbpA
• Bile resistance BSH
• Exoenzyme Mpl PlcA PlcB SMase (L. ivanovii)
• Intracellular growth Hpt LplA1 SvpA

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Virulence FactorsRegulation

• PrfA (Pleiotropic regulatory factor)
• coordinates regulation of the virulence factors
  and is temperature controlled
• Influenced by environment temp., pH, nutrients
  etc.
• The main switch of a regulon including the
  majority of the known listerial virulence genes
  LIPI-1 genes (with prfA itself) and several genes
  of the subfamily of secreted internalins
  (e.g.,inlC of L.monocytogenes and i-inlE of
  L.ivanovii)
• PrfA negatively regulates stress response
  mediator gene clpC and the motility-associated
  genes motA and flaA

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Virulence Factors

• InvasionAuto InlA InlB LpeA p60
• Peptidase Lsp
• RegulationPrfA
• Stress protein ClpC ClpE ClpP
• Toxin LLO LLS

• Actin-based motility ActA
• Adherence Ami FbpA
• Bile resistance BSH
• Exoenzyme Mpl PlcA PlcB SMase (L. ivanovii)
• Intracellular growth Hpt LplA1 SvpA

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Virulence FactorsStress protein

• ClpC An ATPase promoting early escape form the
  phagosome of macrophages
• also required for adhesion and invasion, possibly
  by modulating the expression of InlA,InlB and
  ActA
• ClpE An ATPase required for prolonged survival
  at 42 degree  Acts synergistically with ClpC in
  cell division
• ClpP  Serine protease involved in proteolysis
  and is required for growth under stress
  conditions

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Virulence Factors

• InvasionAuto InlA InlB LpeA p60
• Peptidase Lsp
• Regulation PrfA
• Stress protein ClpC ClpE ClpP
• Toxin LLO LLS

• Actin-based motility ActA
• Adherence Ami FbpA
• Bile resistance BSH
• Exoenzyme Mpl PlcA PlcB SMase (L. ivanovii)
• Intracellular growth Hpt LplA1 SvpA

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Virulence FactorsToxin

• LLO (Listeriolysin O)  Mediates lysis of the
  primary phagosomes formed after the uptake of
  extracellular bacteria, and required for the
  efficient escape from the double-membrane vacuole
  that forms upon cell-to-cell spead  The pores or
  membrane lesions caused by LLO facilitate the
  access of Listeria phospholipases to their
  substrates, leading to total dissolution of the
  physical barrier that delimits the phagosomal
  compartment  Multifunctional virulence factor
  induce a number of host cell responses, such as
  cell proliferation, activation of MAP kinase
  pathway in epithelial cells, modulation of
  internalization via calcium signaling and
  cytokine expression in macrophages, etc.

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34
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• ????? ????? ? ???? ?? ??
• ???? ?????????? ???????? ?? ????? ??' ????????.
• ???????? ?????? ??? ??????? ????? ???? cutaneous
  listeriosis
• ???? ???????

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• 1) ?????? ??????????
• ?????? ????? ?????
• ??????? ??????
• ????? ?-trigeminal nerve ? ???? ???
• nystagmus, blindness, unilateral facial paralysis
• ????? ???????

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2) ?????

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• ????? ???????? ?? ???????
• ??????? ?????
• ????? ???? ?????? neonatal death
• ???? 6 ?? 8 ???? ???? ?????
• ????? 3 ?? 11 " " "
• ????? 20 - 1 ?????
• ??? ( stress )

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• ???? ???? ??? ( ????????? )
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• ??????? ??????? - serosal haemorrhages
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• ???????????????? (?????????) false positive
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• 1-2 ?????? ??????? ???????

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Listeria monocytogenes infection in Israel and
review of cases worldwide

• Emerging Infectious Diseases,  March, 2002  by
  Yardena Siegman-Igra,  Rotem Levin,  Miriam
  Weinberger,  Yoav Golan,  David Schwartz,  Zmira
  Samra,  Hana Konigsberger,  Amos Yinnon,  Galia
  Rahav,  Nathan Keller,  Nail Bisharat,  Jehuda
  Karpuch,  Renato Finkelstein,  Michael Alkan,
   Zvi Landau,  Julia Novikov,  David Hassin,
   Carlos Rudnicki,  Ruth Kitzes,  Shmouel Ovadia,
   Zvi Shimoni,  Ruth Lang,  Tamar Shohat
• Listeria monocytogenes, an uncommon foodborne
  pathogen, is increasingly recognized as a cause
  of life-threatening disease. A marked increase in
  reported cases of listeriosis during 1998
  motivated a retrospective nationwide survey of
  the infection in Israel. From 1995 to 1999, 161
  cases were identified 70 (43) were perinatal
  infections, with a fetal mortality rate of 45.
  Most (74) of the 91 nonperinatal infections
  involved immunocompromised patients with
  malignancies, chronic liver disease, chronic
  renal failure, or diabetes mellitus. The common
  clinical syndromes in these patients were primary
  bacteremia (47) and meningitis (28). The crude
  case-fatality rate in this group was 38, with a
  higher death rate in immuno-compromised patients.