An iron-regulated LysR-type element mediates antimicrobial peptide resistance and virulence in Yersinia pseudotuberculosis

Arafah, Sonia; Rosso, Marie-Laure; Rehaume, Linda; Hancock, Robert E. W.; Simonet, Michel; Marceau, Michaël

doi:10.1099/mic.0.026690-0

Cited by 12 publications

(10 citation statements)

References 51 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additional studies will be needed to differentiate the contributions of the feo genes in iron replenishment and CAMP resistance for the intracellular survival and growth of Y. pestis . Interestingly, another study has recently linked iron uptake with polymyxin B resistance in Y. pseudotuberculosis, a coregulator of the yfe and pbgP genes being responsible for both phenotypes [61]. …”

Section: Discussionmentioning

confidence: 99%

Tn5AraOut mutagenesis for the identification of Yersinia pestis genes involved in resistance towards cationic antimicrobial peptides

Guo

Nair

Galván

et al. 2011

Microbial Pathogenesis

View full text Add to dashboard Cite

Bacterial pathogens display a variety of protection mechanisms against the inhibitory and lethal effects of host cationic antimicrobial peptides (CAMPs). To identify Yersinia pestis genes involved in CAMP-resistance, libraries of DSY101 (KIM6 caf1 pla psa) minitransposon Tn5AraOut mutants were selected at 37°C for resistance to the model CAMPs polymyxin B or protamine. This approach targeted genes that needed to be repressed (null mutations) or induced (upstream PBAD insertions) for the detection of CAMP resistance, and predictably for improved pathogen fitness in mammalian hosts. Ten mutants demonstrated increased resistance to polymyxin B or protamine, with the mapped mutations pointing towards genes suspected to participate in modifying membrane components, genes encoding transport proteins or enzymes, or the regulator of a ferrous iron uptake system (feoC). Not all the mutants were resistant to both CAMPs used for selection. None of the polymyxin B- and only some protamine-resistant mutants, including the feoC mutant, showed increased resistance to rat bonchoalveolar lavage fluid (rBALF) known to contain cathelicidin and β-defensin 1. Thus, findings on bacterial resistance to polymyxin B or protamine don’t always apply to CAMPs of the mammalian innate immune system, such as the ones in rBALF.

show abstract

Section: Discussionmentioning

confidence: 99%

Tn5AraOut mutagenesis for the identification of Yersinia pestis genes involved in resistance towards cationic antimicrobial peptides

Guo

Nair

Galván

et al. 2011

Microbial Pathogenesis

View full text Add to dashboard Cite

show abstract

“…Primers used are listed in Table S4. Control primers were for the 16S rRNA as described previously [82]. Results were analyzed using the Bio-Rad CFX software.…”

Section: Methodsmentioning

confidence: 99%

IscR Is Essential for Yersinia pseudotuberculosis Type III Secretion and Virulence

et al. 2014

View full text Add to dashboard Cite

Type III secretion systems (T3SS) are essential for virulence in dozens of pathogens, but are not required for growth outside the host. Therefore, the T3SS of many bacterial species are under tight regulatory control. To increase our understanding of the molecular mechanisms behind T3SS regulation, we performed a transposon screen to identify genes important for T3SS function in the food-borne pathogen Yersinia pseudotuberculosis. We identified two unique transposon insertions in YPTB2860, a gene that displays 79% identity with the E. coli iron-sulfur cluster regulator, IscR. A Y. pseudotuberculosis iscR in-frame deletion mutant (ΔiscR) was deficient in secretion of Ysc T3SS effector proteins and in targeting macrophages through the T3SS. To determine the mechanism behind IscR control of the Ysc T3SS, we carried out transcriptome and bioinformatic analysis to identify Y. pseudotuberculosis genes regulated by IscR. We discovered a putative IscR binding motif upstream of the Y. pseudotuberculosis yscW-lcrF operon. As LcrF controls transcription of a number of critical T3SS genes in Yersinia, we hypothesized that Yersinia IscR may control the Ysc T3SS through LcrF. Indeed, purified IscR bound to the identified yscW-lcrF promoter motif and mRNA levels of lcrF and 24 other T3SS genes were reduced in Y. pseudotuberculosis in the absence of IscR. Importantly, mice orally infected with the Y. pseudotuberculosis ΔiscR mutant displayed decreased bacterial burden in Peyer's patches, mesenteric lymph nodes, spleens, and livers, indicating an essential role for IscR in Y. pseudotuberculosis virulence. This study presents the first characterization of Yersinia IscR and provides evidence that IscR is critical for virulence and type III secretion through direct regulation of the T3SS master regulator, LcrF.

show abstract

“…81, 90, 91 In Y. pestis, r egulation of yfe by the LysR-type homologue and mntH by OxyR has not been tested.…”

Section: In Vitro and In Silico Analysis Of Transition Metal Transpormentioning

confidence: 99%

The role of transition metal transporters for iron, zinc, manganese, and copper in the pathogenesis of Yersinia pestis

2015

View full text Add to dashboard Cite

Yersinia pestis, the causative agent of bubonic, septicemic and pneumonic plague, encodes a multitude of Fe transport systems. Some of these are defective due to frameshift or IS element insertions, while others are functional in vitro but have no established role in causing infections. Indeed only 3 Fe transporters (Ybt, Yfe and Feo) have been shown to be important in at least one form of plague. The yersiniabactin (Ybt) system is essential in the early dermal/lymphatic stages of bubonic plague, irrelevant in the septicemic stage, and critical in pneumonic plague. Two Mn transporters have been characterized (Yfe and MntH). These two systems play a role in bubonic plague but the double yfe mntH mutant is fully virulent in a mouse model of pneumonic plague. The same in vivo phenotype occurs with a mutant lacking two (Yfe and Feo) of four ferrous transporters. A role for the Ybt siderophore in Zn acquisition has been revealed. Ybt-dependent Zn acquisition uses a transport system completely independent of the Fe-Ybt uptake system. Together Ybt components and ZnuABC play a critical role in Zn acquisition in vivo. Single mutants in either system retain high virulence in a mouse model of septicemic plague while the double mutant is completely avirulent.

show abstract

An iron-regulated LysR-type element mediates antimicrobial peptide resistance and virulence in Yersinia pseudotuberculosis

Cited by 12 publications

References 51 publications

Tn5AraOut mutagenesis for the identification of Yersinia pestis genes involved in resistance towards cationic antimicrobial peptides

Tn5AraOut mutagenesis for the identification of Yersinia pestis genes involved in resistance towards cationic antimicrobial peptides

IscR Is Essential for Yersinia pseudotuberculosis Type III Secretion and Virulence

The role of transition metal transporters for iron, zinc, manganese, and copper in the pathogenesis of Yersinia pestis

Contact Info

Product

Resources

About