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

Fahlgren, Anna; Avican, Kemal; Westermark, Linda; Nordfelth, Roland; Fällman, Maria

doi:10.1128/iai.01793-14

Cited by 37 publications

(55 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, it is very likely that the ΔtatCL mutants that survived in the acidic environment in the stomach were still able to colonize the cecum and PPs at the later time points of infection. Our results also show that, in contrast to the two mutants, wild-type Y. pseudotuberculosis is able to replicate in the host intestine and also reach to MLNs already at 24 hpi, which is in line with the findings of previous studies (31).…”

Section: Discussionsupporting

confidence: 82%

“…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%

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: Discussionsupporting

confidence: 82%

Section: Resultsmentioning

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

“…To explore a potential connection between virulence and plasmid copy-numbers, we first determined plasmid (pIBX) copy-numbers in Y. pseudotuberculosis YpIII (YpIII/pIBX) (13) cultures under different conditions with a PCR-free whole-genome sequencing approach (14).…”

Section: +mentioning

confidence: 99%

Increased plasmid copy number is essential for Yersinia T3SS function and virulence

Wang

Avican

Fahlgren

et al. 2016

Science

Self Cite

View full text Add to dashboard Cite

These authors share the last authorship *Correspondence to: tomas.edgren@umu.se; hans.wolf-watz@umu.se. Abstract:Pathogenic bacteria have evolved numerous virulence mechanisms that are essential for establishing infections. The enterobacteria, Yersinia, uses a Type III Secretion System (T3SS), encoded by a 70-kb, low-copy, IncFII-class virulence plasmid. Here, we report a novel virulence strategy in Y. pseudotuberculosis in which this pathogen up-regulates the plasmid copynumber during infection. We show that increased dose of plasmid-encoded genes is indispensable for virulence and substantially elevates the expression and function of the T3SS.Remarkably, we found direct, tight coupling between plasmid replication and T3SS function.This regulatory pathway provides a framework for further exploration of the environmental sensing mechanisms of pathogenic bacteria.

show abstract

“…In vivo, Yop secretion is triggered by the close interaction between Yersinia and target cells, followed by translocation of virulence effectors into the cytoplasm of the host cell via T3SS (20,21). Mice are a commonly used virulence infection model for Y. pseudotuberculosis, with targeting of the gastrointestinal tract, where the pathogen infects the Peyer's patches of the small intestine and cecal lymphoid aggregates (22)(23)(24). The neutrophils that are subsequently recruited in large numbers to the site of infection have been shown to be the main target for Yop delivery during infection (23).…”

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

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

Cited by 37 publications

References 41 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

Increased plasmid copy number is essential for Yersinia T3SS function and virulence

Yersinia pseudotuberculosis Blocks Neutrophil Degranulation

Contact Info

Product

Resources

About