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Edwardsiella tarda Hfq: impact on host infection and global protein expression.

ABSTRACT: Hfq is an RNA-binding protein that plays an important role in many cellular processes. In this study, we examined the biological effect of the Hfq of Edwardsiella tarda, a severe fish pathogen with a broad host range that includes humans. To facilitate the study, a markerless hfq in-frame deletion wild type, TXhfq, was constructed. Compared to the wild type TX01, TXhfq exhibited (i) retarded planktonic and biofilm growth, (ii) decreased resistance against oxidative stress, (iii) attenuated overall virulence and tissue dissemination and colonization capacity, (iv) impaired ability to replicate in host macrophages and to block host immune response. Introduction of a trans-expressed hfq gene into TXhfq restored the lost virulence of TXhfq. To identify potential Hfq targets, comparative global proteomic analysis was conducted, which revealed that 20 proteins belonging to different functional categories were differentially expressed in TXhfq and TX01. Quantitative real time RT-PCR analysis showed that the mRNA levels of two thirds of the genes of the identified proteins were consistent with the proteomic results. Since TXhfq is dramatically attenuated in virulence, we further examined its potential as a naturally delivered vaccine administered via the immersion route in a flounder model. The results showed that TXhfq induced effective protection against lethal E. tarda challenge. Taken together, our study indicated that Hfq is required for the normal operation of E. tarda in multiple aspects, and that Hfq probably exerts a regulatory effect on a wide range of target genes at both transcription and post-transcription levels.

SUBMITTER: Hu YH

PROVIDER: S-EPMC4015145 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Edwardsiella tarda Hfq: impact on host infection and global protein expression.

Hu Yong-Hua YH Li Yong-Xin YX Sun Li L

Veterinary research 20140225

Hfq is an RNA-binding protein that plays an important role in many cellular processes. In this study, we examined the biological effect of the Hfq of Edwardsiella tarda, a severe fish pathogen with a broad host range that includes humans. To facilitate the study, a markerless hfq in-frame deletion wild type, TXhfq, was constructed. Compared to the wild type TX01, TXhfq exhibited (i) retarded planktonic and biofilm growth, (ii) decreased resistance against oxidative stress, (iii) attenuated overa ...[more]

PMID: 24568370

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Project description:UnlabelledEdwardsiella tarda is an important pathogenic bacterium that can replicate in macrophages. However, how the intramacrophage infection process affects the virulence of this bacterium is essentially unknown. Here, we show that E. tarda replicates and induces a caspase-1-dependent cell pyroptosis in a murine macrophage model. Via pyroptosis, intracellular E. tarda escapes to the extracellular milieu, forming a unique bacterial population. Being different from the bacteria cultured alone, this unique population possesses a reprogrammed transcriptional profile, particularly with upregulated type III secretion system (T3SS)/T6SS cluster genes. Subsequent studies revealed that the macrophage-released population gains enhanced infectivity for host epithelial cells and increases resistance to multiple host defenses and hence displays significantly promoted virulence in vivo Further studies indicated that T3SS is essentially required for the macrophage infection process, while T6SS contributes to infection-induced bacterial virulence. Altogether, this work demonstrates that E. tarda can utilize macrophages as a niche for virulence priming and for spreading infection, suggesting a positive role for intramacrophage infection in bacterial pathogenesis.ImportanceMany pathogens can replicate in macrophages, which is crucial for their pathogenesis. To survive in the macrophage cell, pathogens are likely to require fitness genes to counteract multiple host-killing mechanisms. Here, Edwardsiella tarda is proved to exit from macrophages during infection. This macrophage-released population displays a reprogrammed transcriptional profile with significantly upregulated type III secretion system (T3SS)/T6SS-related genes. Furthermore, both enhanced infectivity in epithelial cells and activated resistance to complex host defenses were conferred on this macrophage-primed population, which consequently promoted the full virulence of E. tarda in vivo Our work provides evidence that E. tarda can utilize macrophages as a niche for virulence priming and for spreading infection, highlighting the importance of the intramacrophage infection cycle for the pathogenesis of E. tarda.

Dataset Information

Edwardsiella tarda Hfq: impact on host infection and global protein expression.

Publications

Edwardsiella tarda Hfq: impact on host infection and global protein expression.

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