Yersinia pseudotuberculosis Efficiently Escapes Polymorphonuclear Neutrophils during Early Infection

Westermark, Linda; Fahlgren, Anna; Fällman, Maria

doi:10.1128/iai.01634-13

Cited by 27 publications

(30 citation statements)

References 46 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Bioluminescent in vivo imaging (BLI) allows the detection, visual characterization, and semiquantification of bacteria during infection of mice in real time (29). This method has widely been used to monitor Y. pseudotuberculosis YPIII infections using an in vivo imaging spectrum (IVIS) for BLI analysis (30)(31)(32)(33). To allow similar studies in strain IP32953, we constructed bioluminescent variants of the wild-type strain and the ΔtatC and ΔsufI mutant strains by integration of the complete lux operon from Photorhabdus luminescens into the 16S rRNA gene using a thermosensitive plasmid, p16Slux.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, we found that the wtL strain formed large numbers of foci and that some of them were not surrounded by neutrophils, which could make it possible for these bacteria to spread and cause systemic infection. The T3SS effectors YopH, YopE, and YopK are essential for the targeting of and escape from neutrophils during early infection (30). Our previous studies showed that the T3SS function was not affected in the ΔtatC mutant (22,23).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Tat Substrate SufI Is Critical for the Ability of Yersinia pseudotuberculosis To Cause Systemic Infection

et al. 2017

Self Cite

View full text Add to dashboard Cite

The twin arginine translocation (Tat) system targets folded proteins across the inner membrane and is crucial for virulence in many important humanpathogenic bacteria. Tat has been shown to be required for the virulence of Yersinia pseudotuberculosis, and we recently showed that the system is critical for different virulence-related stress responses as well as for iron uptake. In this study, we wanted to address the role of the Tat substrates in in vivo virulence. Therefore, 22 genes encoding potential Tat substrates were mutated, and each mutant was evaluated in a competitive oral infection of mice. Interestingly, a ΔsufI mutant was essentially as attenuated for virulence as the Tat-deficient strain. We also verified that SufI was Tat dependent for membrane/periplasmic localization in Y. pseudotuberculosis. In vivo bioluminescent imaging of orally infected mice revealed that both the ΔsufI and ΔtatC mutants were able to colonize the cecum and Peyer's patches (PPs) and could spread to the mesenteric lymph nodes (MLNs). Importantly, at this point, neither the ΔtatC mutant nor the ΔsufI mutant was able to spread systemically, and they were gradually cleared. Immunostaining of MLNs revealed that both the ΔtatC and ΔsufI mutants were unable to spread from the initial infection foci and appeared to be contained by neutrophils, while wild-type bacteria readily spread to establish multiple foci from day 3 postinfection. Our results show that SufI alone is required for the establishment of systemic infection and is the major cause of the attenuation of the ΔtatC mutant.KEYWORDS Yersinia pseudotuberculosis, Tat pathway, virulence, SufI, mesenteric lymph nodes, neutrophils T he genus Yersinia includes three species that are pathogenic to humans: Yersinia pestis, the causative agent of plague, and the two enteropathogens Y. enterocolitica and Y. pseudotuberculosis, which normally cause a self-limiting disease with symptoms ranging from mild diarrhea, enterocolitis, septicemia, and mesenteric lymphadenitis to reactive arthritis in humans after ingestion of contaminated food or water (1). Once it is ingested, Y. pseudotuberculosis traverses the epithelial barrier through M cells and infects the associated lymphoid tissues, such as Peyer's patches (PPs) and cecal patches, and later spreads to the mesenteric lymph nodes (MLNs). Although the infection is usually self-limited in humans, the infection caused by the two enteropathogenic Yersinia species in mice readily progresses to become systemic and disseminates to the spleen and liver (2). The main virulence arsenal of Yersinia is the type III secretion system (T3SS), which is encoded by an ϳ70-kb virulence plasmid. The T3SS enables the translocation of virulence effector proteins directly into the cytosol of the target host cell, which results in the disruption of host signaling and early immune

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Tat Substrate SufI Is Critical for the Ability of Yersinia pseudotuberculosis To Cause Systemic Infection

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Given the presence of PMNs around bacterial foci in the cecal aggregates and the previously demonstrated importance of YopH and YopE for the antiphagocytic capacity of Y. pseudotuberculosis against PMNs (20,35,36), it was not surprising that these effectors together were found to be important for initial establishment of infection, which is a prerequisite for the development of persistent infection. Further, by using universal markers, we could not reveal any obvious effects on T cells, B cells, macrophages, and dendritic cells during the persistent state.…”

mentioning

confidence: 99%

Colonization of Cecum Is Important for Development of Persistent Infection by Yersinia pseudotuberculosis

et al. 2014

Self Cite

View full text Add to dashboard Cite

bYersiniosis is a human disease caused by the bacterium Yersinia pseudotuberculosis or Yersinia enterocolitica. The infection is usually resolved but can lead to postinfectious sequelae, including reactive arthritis and erythema nodosum. The commonly used Yersinia mouse infection model mimics acute infection in humans to some extent but leads to systemic infection and eventual death. Here, we analyzed sublethal infection doses of Y. pseudotuberculosis in mice in real time using bioluminescent imaging and found that infections using these lower doses result in extended periods of asymptomatic infections in a fraction of mice. In a search for the site for bacterial persistence, we found that the cecum was the primary colonization site and was the site where the organism resided during a 115-day infection period. Persistent infection was accompanied by sustained fecal shedding of cultivable bacteria. Cecal patches were identified as the primary site for cecal colonization during persistence. Y. pseudotuberculosis bacteria were present in inflammatory lesions, in localized foci, or as single cells and also in neutrophil exudates in the cecal lumen. The chronically colonized cecum may serve as a reservoir for dissemination of infection to extraintestinal sites, and a chronic inflammatory state may trigger the onset of postinfectious sequelae. This novel mouse model for bacterial persistence in cecum has potential as an investigative tool to unveil a deeper understanding of bacterial adaptation and host immune defense mechanisms during persistent infection.

show abstract

“…Previously we have shown that Y. pseudotuberculosis efficiently evades neutrophilic attack in the early stages of infection and that mice with reduced numbers of neutrophils are more sensitive to initial bacterial colonization (32), indicating that neutrophil escape is an important feature of virulent Yersinia species. While it is well appreciated that Y. pseudotuberculosis resists phagocytic engulfment by both neutrophils and macrophages (33,34), less is known about how this pathogen faces the challenge posed by neutrophil degranulation.…”

mentioning

confidence: 99%

Yersinia pseudotuberculosis Blocks Neutrophil Degranulation

2016

Self Cite

View full text Add to dashboard Cite

bNeutrophils are essential components of immunity and are rapidly recruited to infected or injured tissue. Upon their activation, neutrophils release granules to the cell's exterior, through a process called degranulation. These granules contain proteins with antimicrobial properties that help combat infection. The enteropathogenic bacterium Yersinia pseudotuberculosis successfully persists as an extracellular bacterium during infection by virtue of its translocation of virulence effectors (Yersinia outer proteins [Yops]) that act in the cytosol of host immune cells to subvert phagocytosis and proinflammatory responses. Here, we investigated the effect of Y. pseudotuberculosis on neutrophil degranulation upon cell contact. We found that virulent Y. pseudotuberculosis was able to prevent secondary granule release. The blocking effect was general, as the release of primary and tertiary granules was also reduced. Degranulation of secondary granules was also blocked in primed neutrophils, suggesting that this mechanism could be an important element of immune evasion. Further, wild-type bacteria conferred a transient block on neutrophils that prevented their degranulation upon contact with plasmid-cured, avirulent Y. pseudotuberculosis and Escherichia coli. Detailed analyses showed that the block was strictly dependent on the cooperative actions of the two antiphagocytic effectors, YopE and YopH, suggesting that the neutrophil target structures constituting signaling molecules needed to initiate both phagocytosis and general degranulation. Thus, via these virulence effectors, Yersinia can impair several mechanisms of the neutrophil's antimicrobial arsenal, which underscores the power of its virulence effector machinery. N eutrophils are an important element of the innate immune response. Circulating neutrophils are recruited into tissues upon injury or infection in order to play key roles in the defense against bacterial or fungal pathogens. Several mechanisms are used to eliminate microbial invaders such as phagocytosis, neutrophil extracellular trap (NET) formation, and degranulation. Degranulation is triggered upon the activation of neutrophils by microbial or inflammatory stimuli and leads to the release of granule contents. Neutrophils contain four types of granules and are categorized as peroxidase-positive (azurophilic or primary) granules, peroxidase-negative (specific or secondary, and gelatinase or tertiary) granules, and secretory vesicles (1, 2). Secretory vesicles and tertiary granules are released during adhesion and transmigration through the endothelium, respectively, whereas the primary and secondary granules hold the majority of the cell's antimicrobial activity and are released at the infectious site (1-3). Primary granules contain high quantities of myeloperoxidase (MPO), as well as defensins, elastase, heparin binding proteins, and proteinases. Secondary granules are rich in lactoferrin and enzymes such as collagenase and gelatinase, as well as the LL-37 precursor hCAP-18. However, these granules...

show abstract

Yersinia pseudotuberculosis Efficiently Escapes Polymorphonuclear Neutrophils during Early Infection

Cited by 27 publications

References 46 publications

The Tat Substrate SufI Is Critical for the Ability of Yersinia pseudotuberculosis To Cause Systemic Infection

The Tat Substrate SufI Is Critical for the Ability of Yersinia pseudotuberculosis To Cause Systemic Infection

Colonization of Cecum Is Important for Development of Persistent Infection by Yersinia pseudotuberculosis

Yersinia pseudotuberculosis Blocks Neutrophil Degranulation

Contact Info

Product

Resources

About