All Yersinia Are Not Created Equal: Phenotypic Adaptation to Distinct Niches Within Mammalian Tissues

Davis, Kimberly M.

doi:10.3389/fcimb.2018.00261

Cited by 31 publications

(26 citation statements)

References 77 publications

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“…The effectors counteract innate immunity and are required for Yersinia to colonize and replicate as extracellular microcolonies in lymph nodes, the preferred target tissue for these pathogens. For recent reviews on the pathogenesis of Y. pestis , Y. enterocolitica , and Y. pseudotuberculosis , see 39‐41.…”

Section: The Pyrin‐yersinia Effector Interactionmentioning

confidence: 99%

“…Effectors are preferentially translocated into phagocytes 40 . This target cell specificity is due in part to the fact that neutrophils and inflammatory monocytes are recruited in large numbers to sites of Yersinia infection and make direct contact with the bacteria 39,40 . This cellular recruitment results in the formation of granuloma‐like structures, variously characterized histopathologically as microabscesses, necrotic lesions, or pyogranulomas 42,43 .…”

Section: The Pyrin‐yersinia Effector Interactionmentioning

confidence: 99%

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The pyrin inflammasome and the Yersinia effector interaction

Malik

Bliska

2020

Immunological Reviews

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Pyrin is a cytosolic pattern‐recognition receptor that normally functions as a guard to trigger capase‐1 inflammasome assembly in response to bacterial toxins and effectors that inactivate RhoA. The MEFV gene encoding human pyrin is preferentially expressed in phagocytes. Key domains in pyrin include a pyrin domain (PYD), a linker region, and a B30.2 domain. Binding of ASC to pyrin by a PYD‐PYD interaction triggers inflammasome assembly. Pyrin is held in an inactive conformation by negative regulation mechanisms to avoid premature inflammasome assembly. One mechanism of negative regulation involves phosphorylation of the linker by PRK kinase which in turn is positively regulated by active RhoA. The B30.2 domain also negatively regulates pyrin. Gain of function mutations in MEFV responsible for the autoinflammatory disease Familial Mediterranean Fever (FMF) map to exon 10 encoding the B30.2 domain. Insights into pyrin regulation have come from studies of several Yersinia effectors, which are injected into phagocytes and interact with the RhoA‐PRK‐pyrin axis during infection. Two effectors, YopE and YopT, inactivate RhoA to disrupt phagocytic signaling. To counteract an effector‐triggered immune response, a third effector, YopM, binds to and inhibits pyrin by hijacking PRK and RSK and directing linker phosphorylation. Inhibition of pyrin by YopM is required for virulence of Yersinia pestis, the agent of plague. Recent results from infection studies with human phagocytes and mice producing pyrin B30.2 FMF variants show that gain of function MEFV mutations bypass inhibition by YopM. Population genetic data suggest that MEFV mutations were selected for in individuals of Mediterranean decent during historic plague pandemics. This review discusses current concepts of pyrin regulation and its interaction with Yersinia effectors.

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Section: The Pyrin‐yersinia Effector Interactionmentioning

confidence: 99%

Section: The Pyrin‐yersinia Effector Interactionmentioning

confidence: 99%

The pyrin inflammasome and the Yersinia effector interaction

Malik

Bliska

2020

Immunological Reviews

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“…Two of the best-characterized adhesins in the genus Yersinia are YadA and invasin. Yersinia pseudotuberculosis and Yersinia enterocolitica utilize invasin and YadA to establish infection in the small intestine ( 4 ). Invasin binds β1 integrins on M cells, promoting internalization of the enteropathogenic Yersinia organisms ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Tn-Seq Analysis Identifies Genes Important for Yersinia pestis Adherence during Primary Pneumonic Plague

Eichelberger

Sepúlveda

Ford

et al. 2020

mSphere

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Following inhalation, Yersinia pestis rapidly colonizes the lung to establish infection during primary pneumonic plague. Although several adhesins have been identified in Yersinia spp., the factors mediating early Y. pestis adherence in the lung remain unknown. To identify genes important for Y. pestis adherence during primary pneumonic plague, we used transposon insertion sequencing (Tn-seq). Wild-type and capsule mutant (Δcaf1) Y. pestis transposon mutant libraries were serially passaged in vivo to enrich for nonadherent mutants in the lung using a mouse model of primary pneumonic plague. Sequencing of the passaged libraries revealed six mutants that were significantly enriched in both the wild-type and Δcaf1 Y. pestis backgrounds. The enriched mutants had insertions in genes that encode transcriptional regulators, chaperones, an endoribonuclease, and YPO3903, a hypothetical protein. Using single-strain infections and a transcriptional analysis, we identified a significant role for YPO3903 in Y. pestis adherence in the lung and showed that YPO3903 regulated transcript levels of psaA, which encodes a fimbria previously implicated in Y. pestis adherence in vitro. Deletion of psaA had a minor effect on Y. pestis adherence in the lung, suggesting that YPO3903 regulates other adhesins in addition to psaA. By enriching for mutations in genes that regulate the expression or assembly of multiple genes or proteins, we obtained screen results indicating that there may be not just one dominant adhesin but rather several factors that contribute to early Y. pestis adherence during primary pneumonic plague. IMPORTANCE Colonization of the lung by Yersinia pestis is a critical first step in establishing infection during primary pneumonic plague, a disease characterized by high lethality. However, the mechanisms by which Y. pestis adheres in the lung after inhalation remain elusive. Here, we used Tn-seq to identify Y. pestis genes important for adherence early during primary pneumonic plague. Our mutant enrichment strategy resulted in the identification of genes important for regulation and assembly of genes and proteins rather than adhesin genes themselves. These results reveal that there may be multiple Y. pestis adhesins or redundancy among adhesins. Identifying the adhesins regulated by the genes identified in our enrichment screen may reveal novel therapeutic targets for preventing Y. pestis adherence and the subsequent development of pneumonic plague.

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“…Yersinia pseudotuberculosis (Yptb) is a Gram-negative, extracellular bacterium that is pathogenic to humans and mice (Davis, 2018;Galindo et al, 2011). Yptb is transmitted via the fecal-oral route.…”

Section: Introductionmentioning

confidence: 99%

“…Infection typically causes self-limiting gastroenteritis and mesenteric lymphadenitis. In mice, and occasionally in humans, Yptb spreads to the liver and spleen and causes systemic disease leading to sepsis (Davis, 2018;Galindo et al, 2011;Mikula et al, 2012). The ability of Yptb to multiply in lymphoid tissues and spread to systemic organs depends on the presence of pYV, a virulence plasmid that encodes type III secretion system (T3SS) and several effector proteins called Yersinia outer proteins (Yops).…”

Section: Introductionmentioning

confidence: 99%

Leptin signaling regulates physiological damage and host-pathogen cooperation

Sanchez

Troha

Stengel

et al. 2020

Preprint

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To combat infections, hosts employ a combination of antagonistic and cooperative defense strategies. The former refers to pathogen killing mediated by resistance mechanisms, while the latter refers to physiological defense mechanisms that promote host health during infection independent of pathogen killing, leading to an apparent cooperation between the host and the pathogen. Previous work has shown that leptin, a pleiotropic hormone that plays a central role in regulating appetite and energy metabolism, is indispensable for resistance mechanisms, while a role for leptin signaling in cooperative host-pathogen interactions remains unknown. Using a mouse model of Yersinia pseudotuberculosis (Yptb) infection, the causative agent of Far East scarlet-like fever, we unexpectedly found that genetic inhibition of leptin signaling conferred protection from Yptb infection due to increased host-pathogen cooperation rather than greater resistance defenses. The protection against Yptb infection was not due to differences in food consumption, lipolysis or fat mass. Furthermore, we found that the survival advantage was associated with increased liver damage and dysfunction. Our work reveals an additional level of complexity for the role of leptin in infection defense and suggests that in some contexts, in addition to tolerating the pathogen, tolerating organ damage and dysfunction is more beneficial for survival than preventing the damage.

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All Yersinia Are Not Created Equal: Phenotypic Adaptation to Distinct Niches Within Mammalian Tissues

Cited by 31 publications

References 77 publications

The pyrin inflammasome and the Yersinia effector interaction

The pyrin inflammasome and the Yersinia effector interaction

Tn-Seq Analysis Identifies Genes Important for Yersinia pestis Adherence during Primary Pneumonic Plague

Leptin signaling regulates physiological damage and host-pathogen cooperation

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