The haemin storage (Hms+) phenotype of Yersinia pestis is not essential for the pathogenesis of bubonic plague in mammals

LillardJr, James W.; Bearden, Scott W.; Fetherston, Jacqueline D.; Perry, Robert D.

doi:10.1099/13500872-145-1-197

Cited by 64 publications

(72 citation statements)

References 63 publications

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“…This is required for colonization and eventual blockage of the flea proventriculus -allowing efficient transmission of plague from some fleas, like the oriental rat flea, to mammals (Bacot & Martin, 1914;Bacot, 1915;Hinnebusch et al, 1996;Lillard et al, 1997Lillard et al, , 1999Pendrak & Perry, 1991Perry et al, 1990Perry et al, , 1993Perry et al, , 2004Perry & Fetherston, 1997;Pollitzer, 1954). Biofilm formation is not involved in mammalian virulence -an in-frame deletion in hmsR did not affect the LD 50 in a bubonic plague model .…”

Section: Introductionmentioning

confidence: 99%

Identification of critical amino acid residues in the plague biofilm Hms proteins

et al. 2006

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Yersinia pestis biofilm formation causes massive adsorption of haemin or Congo red in vitro as well as colonization and eventual blockage of the flea proventriculus in vivo. This blockage allows effective transmission of plague from some fleas, like the oriental rat flea, to mammals. Four Hms proteins, HmsH, HmsF, HmsR and HmsS, are essential for biofilm formation, with HmsT and HmsP acting as positive and negative regulators, respectively. HmsH has a β-barrel structure with a large periplasmic domain while HmsF possesses polysaccharide deacetylase and COG1649 domains. HmsR is a putative glycosyltransferase while HmsS has no recognized domains. In this study, specific amino acids within conserved domains or within regions of high similarity in HmsH, HmsF, HmsR and HmsS proteins were selected for site-directed mutagenesis. Some but not all of the substitutions in HmsS and within the periplasmic domain of HmsH were critical for protein function. Substitutions within the glycosyltransferase domain of HmsR and the deacetylase domain of HmsF abolished biofilm formation in Y. pestis. Surprisingly, substitution of highly conserved residues within COG1649 did not affect HmsF function.

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Section: Introductionmentioning

confidence: 99%

Identification of critical amino acid residues in the plague biofilm Hms proteins

et al. 2006

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“…Y. pestis biofilms, in which bacteria are surrounded by a self-synthesized polysaccharide-rich matrix, appear to be made only when the bacteria colonize fleas. Several proteins required for Y. pestis biofilms are proteolytically degraded at mammalian body temperatures (25), in vitro biofilms are greatly diminished at 37°C, and a Y. pestis strain defective for biofilm genes was nevertheless highly virulent in a mouse infection (3,22,32).…”

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confidence: 99%

The Yersinia pestis Rcs Phosphorelay Inhibits Biofilm Formation by Repressing Transcription of the Diguanylate Cyclase Gene hmsT

et al. 2012

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c Yersinia pestis, which causes bubonic plague, forms biofilms in fleas, its insect vectors, as a means to enhance transmission. Biofilm development is positively regulated by hmsT, encoding a diguanylate cyclase that synthesizes the bacterial second messenger cyclic-di-GMP. Biofilm development is negatively regulated by the Rcs phosphorelay signal transduction system. In this study, we show that Rcs-negative regulation is accomplished by repressing transcription of hmsT. Yersinia pestis, the agent of bubonic plague, infects fleas, its vectors, by producing bacterial biofilms that can colonize the insect foregut (19). Growth of the biofilm interferes with blood feeding by the infected fleas and potentiates regurgitative transmission. Complete blockage of the foregut by the bacterial biofilm can occur, and blocked fleas bite mammals repeatedly in futile feeding attempts, further enhancing transmission. Y. pestis biofilms, in which bacteria are surrounded by a self-synthesized polysaccharide-rich matrix, appear to be made only when the bacteria colonize fleas. Several proteins required for Y. pestis biofilms are proteolytically degraded at mammalian body temperatures (25), in vitro biofilms are greatly diminished at 37°C, and a Y. pestis strain defective for biofilm genes was nevertheless highly virulent in a mouse infection (3,22,32).Y. pestis biofilms are positively regulated by cyclic-di-GMP (cdi-GMP), which is synthesized by diguanylate cyclase (DGC) enzymes. The Y. pestis genome encodes several putative DGCs, but only two of them, HmsT and Y3730, are related to biofilm formation (3,8,22,32). Yersinia pseudotuberculosis, a bacterium closely related to Y. pestis, also makes biofilms that are regulated by hmsT (10). The biofilm-promoting activity of c-di-GMP has not been determined, but in other systems, c-di-GMP has been shown to be an allosteric activator of glycosyltransferases (27,28).Y. pestis and Y. pseudotuberculosis biofilms are negatively regulated by the Rcs phosphorelay system (33). Rcs consists of two membrane-bound proteins, RcsC and RcsD, a DNA-binding response regulator, RcsB, and an accessory protein, RcsA. In phosphorelays of this type, outputs can be dependent on RcsB alone, acting in homodimers, or on heterodimers of RcsB and RcsA (23). Genetic investigation showed that in Y. pestis, rcsA is a nonfunctional pseudogene, while in Y. pseudotuberculosis, rcsA is functional and represses biofilms (33). Although rcsD has a frameshift in Y.pestis, it is still functional and may dephosphorylate RcsB to derepress biofilms (33).The factors determining hmsT transcription have not been examined. In the present study, we show that in Y. pestis and Y. pseudotuberculosis, Rcs represses hmsT transcription. MATERIALS AND METHODSBacterial strains and plasmids. The strains and plasmids used are shown in Table 1. CDY497 was made by a method to insert PCR products into the chromosome using the Red recombination system (11, 33). For strains containing ⌬lacZ::Cm, the same method was used, after which reporter constr...

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“…At least two haemin storage loci (hmsHFRS and hmsT) enable Yersinia pestis to accumulate haemin, ferric iron and Congo Red in a process that is only active at temperatures lower than 34°C (Perry et al, 1990;Lillard et al, 1999). Interestingly, as recently shown by Perry et al (2004), thermal control of the Hms+ phenotype is unlikely to depend on transcriptional regulation for at least two reasons.…”

Section: Haemin Storage: Its Unusual Regulation By Temperature and Ironmentioning

confidence: 84%

Transcriptional Regulation inYersinia: An UpdateYersinia: An Update

2005

Current Issues in Molecular Biology

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In response to the ever-present need to adapt to environmental stress, bacteria have evolved complex (and often overlapping) regulatory networks that respond to various changes in growth conditions, including entry into the host. The expression of most bacterial virulence factors is regulated; thus the question of how bacteria orchestrate this process has become a recurrent research theme for every bacterial pathogen, and the three pathogenic Yersinia are no exception. The earliest studies of regulation in these species were prompted by the characterization of plasmid-encoded virulence determinants, and those conducted since have continued to focus on the principal aspects of virulence in these pathogens. Most Yersinia virulence factors are thermally regulated, and are active at either 28°C (the optimal growth temperature) or 37°C (the host temperature). However, regulation by this omnipresent thermal stimulus occurs through a wide variety of mechanisms, which generally act in conjunction with (or are modulated by) additional controls for other environmental cues such as pH, ion concentration, nutrient availability, osmolarity, oxygen tension and DNA damage. Yersinia's recent entry into the genome sequencing era has given scientists the opportunity to study these regulators on a genome-wide basis. This has prompted the first attempts to establish links between the presence or absence of regulatory elements and the three pathogenic species' respective lifestyles and degrees of virulence. IntroductionCompared to cells of multicellular organisms, microorganisms face a significant additional challenge: they encounter a wide array of sudden, intense and sometimes even life-threatening environmental changes, and must therefore rapidly modify their structure and metabolism accordingly. Although other mechanisms exist, these changes in bacterial physiology mainly occur by regulating the production of the appropriate structural proteins and enzymes. Adaptation of gene expression in response to such situations appears to be essential for bacterial survival, and thus the regulators involved in these processes should be treated as being as important as the effectors themselves. In bacterial pathogens like those of the Yersinia genus, most outside-to-inside stressinduced responses lead to changes in the expression of virulence factors. In fact, most of the known Yersinia virulence genes are regulated, and elements controlling their expression are thus also virulence factors.All regulatory systems have a common purpose: to create an interface between the perception of one or several stimuli and to activate or repress expression of their cognate effectors. As we will see by reviewing what is known about Yersinia, the means used to regulate the production of a given bacterial factor range from very simple mechanisms (where the DNA-binding properties of the transcriptional regulator are directly altered by the stimulus) to extremely complex systems which sometimes require lengthy signal transduction cascades and/or simul...

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The haemin storage (Hms+) phenotype of Yersinia pestis is not essential for the pathogenesis of bubonic plague in mammals

Cited by 64 publications

References 63 publications

Identification of critical amino acid residues in the plague biofilm Hms proteins

Identification of critical amino acid residues in the plague biofilm Hms proteins

The Yersinia pestis Rcs Phosphorelay Inhibits Biofilm Formation by Repressing Transcription of the Diguanylate Cyclase Gene hmsT

Transcriptional Regulation inYersinia: An UpdateYersinia: An Update

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