Role of Yersinia pestis Toxin Complex Family Proteins in Resistance to Phagocytosis by Polymorphonuclear Leukocytes

Spinner, Justin L.; Carmody, Aaron B.; Jarrett, Clayton O.; Hinnebusch, B. Joseph

doi:10.1128/iai.00648-13

Cited by 25 publications

(18 citation statements)

References 55 publications

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“…In this study, we show that pCD1 ϩ and pCD1 Ϫ Y. pestis, cultured at 21°C, is internalized, and a portion of intracellular bacteria remains viable within PMNs. Under similar infection conditions, pCD1 ϩ Y. pestis, grown at 37°C, is more resistant to phagocytosis, with 60 -65% intracellular after 1 h of incuba-tion with human PMNs [24] compared with 75-90% intracellular when grown at 21°C [44]. Similar to our findings with Y. pestis grown at 21°C, ϳ30% of the pCD1 ϩ Y. pestis grown at 37°C that is internalized is still viable 4 h after phagocytosis [24].…”

Section: Discussionsupporting

confidence: 86%

Yersinia pestissurvival and replication within human neutrophil phagosomes and uptake of infected neutrophils by macrophages

Spinner

Winfree

Starr

et al. 2013

Journal of Leukocyte Biology

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Yersinia pestis, the bacterial agent of plague, is transmitted by fleas. The bite of an infected flea deposits Y. pestis into the dermis and triggers recruitment of innate immune cells, including phagocytic PMNs. Y. pestis can subvert this PMN response and survive at the flea-bite site, disseminate, and persist in the host. Although its genome encodes a number of antiphagocytic virulence factors, phagocytosis of Y. pestis by PMNs has been observed. This study tests the hypotheses that Y. pestis, grown at the ambient temperature of the flea vector (21°C), where the major antiphagocytic virulence factors are not produced, can survive and replicate within human PMNs and can use PMNs as a route to infect macrophages subsequently. We show that Y. pestis is localized within PMN phagosomes, predominately as individual bacteria, and that intracellular bacteria can survive and replicate. Within 12 h of infection, ~70% of infected PMNs had PS on their surface and were plausibly competent for efferocytosis. With the use of live cell confocal imaging, we show that autologous HMDMs recognize and internalize infected PMNs and that Y. pestis survives and replicates within these HMDMs following efferocytosis. Addition of HMDMs to infected PMNs resulted in decreased secretion of inflammatory cytokines (compared with HMDMs incubated directly with pCD1(-) Y. pestis) and increased secretion of the anti-inflammatory cytokine IL-1ra. Thus, Y. pestis can survive and replicate within PMNs, and infected PMNs may be a route for noninflammatory infection of macrophages.

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Section: Discussionsupporting

confidence: 86%

Yersinia pestissurvival and replication within human neutrophil phagosomes and uptake of infected neutrophils by macrophages

Spinner

Winfree

Starr

et al. 2013

Journal of Leukocyte Biology

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“…In particular, conditions (5) and (6) indicate that this mechanism is likely to promote the evolution of blockage. Recent experimental studies have explored the outcome of competition between different strains of Y. pestis in fleas (Rempe et al 2012;Spinner et al 2013;Vadyvaloo and Hinz 2015;Fukuto et al 2018). These studies revealed that fitness costs are associated with mutations in several genes involved in flea-borne transmission (hfq (Rempe et al 2012), rovM (Vadyvaloo and Hinz 2015), and phoP (Fukuto et al 2018)).…”

mentioning

confidence: 99%

To block or not to block: The adaptive manipulation of plague transmission

2019

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The ability of the agent of plague, Yersinia pestis , to form a biofilm blocking the gut of the flea has been considered to be a key evolutionary step in maintaining flea‐borne transmission. However, blockage decreases dramatically the life expectancy of fleas, challenging the adaptive nature of blockage. Here, we develop an epidemiological model of plague that accounts for its different transmission routes, as well as the within‐host competition taking place between bacteria within the flea vector. We use this theoretical framework to identify the environmental conditions promoting the evolution of blockage. We also show that blockage is favored at the onset of an epidemic, and that the frequencies of bacterial strains exhibiting different strategies of blockage can fluctuate in seasonal environments. This analysis quantifies the contribution of different transmission routes in plague and makes testable predictions on the adaptive nature of blockage.

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“…The hypothesis that the Tc proteins are exported via the type III secretion system as suggested by Gendlina et al . () was recently challenged (Hinchliffe et al ., ; Spinner et al ., ).…”

Section: Introductionmentioning

confidence: 97%

“…In Y. pseudotuberculosis strain IP32953, the Tc subunit types A and B have been shown to be transcribed and secreted at 30°C to 37°C, whereas the enzymatically active component C is constitutively expressed (Waterfield et al ., ; Hares et al ., ). The insecticidal factors of Y. pestis are produced only below 37°C and confer increased resistance of this pathogen to killing by polymorphonuclear leucocytes (Spinner et al ., 2012; 2013). The hypothesis that the Tc proteins are exported via the type III secretion system as suggested by Gendlina et al .…”

Section: Introductionmentioning

confidence: 99%

YmoA negatively controls the expression of insecticidal genes in Yersinia enterocolitica

Starke

Fuchs

2014

Molecular Microbiology

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SummaryYersinia enterocolitica is toxic towards invertebrates due to the presence of the toxin complex (tc) genes that are activated by the thermolabile regulator TcaR2. In the search for further regulatory factors involved in insecticidal gene expression, the modulator of yersinial virulence, YmoA, was identified to silence all tc genes of the Y. enterocolitica strain W22703 (biovar 2, serovar O:9). Using promoter fusions with the luciferase reporter, we found that the deletion of ymoA results in elevated transcription of tcaR1, tcaR2, tcaA, tcaB, tcaC, tccC1 and tccC2 at both 15°C and 37°C. Complementation by episomal ymoA significantly reduced tc gene expression, thus validating the inhibitory activity of YmoA on the production of insecticidal proteins. YmoA contributes to the binding properties of H-NS to the tc promoters by forming a complex with this nucleoid-associated protein, and this complex not only binds to the upstream regions of all tc genes, but also to intragenic sites of tcaA and tcaB that play an important role in controlling the expression of both genes. At low temperature, the intracellular amount of thermostable YmoA is not reduced, but the repressor is less functional. These data point to H-NS/YmoA as an antagonist of the inducer TcaR2.

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Role of Yersinia pestis Toxin Complex Family Proteins in Resistance to Phagocytosis by Polymorphonuclear Leukocytes

Cited by 25 publications

References 55 publications

Yersinia pestissurvival and replication within human neutrophil phagosomes and uptake of infected neutrophils by macrophages

Yersinia pestissurvival and replication within human neutrophil phagosomes and uptake of infected neutrophils by macrophages

To block or not to block: The adaptive manipulation of plague transmission

YmoA negatively controls the expression of insecticidal genes in Yersinia enterocolitica

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