ROBERT DONALD PERRY

..This suggests that Mn availability, bacterial Mn requirements or Mn transporters used by Y. pestis are different in the lungs (pneumonic plague) compared with systemic disease...

..The Ybt system is essential for the ability of Yersinia pestis to cause bubonic plague and important in pneumonic plague as well. However, the ability to cause fatal septicemic plague is independent of Ybt...

..1 cells. These results suggest that the Yfe and Feo systems are somewhat redundant ferrous iron transporters capable of iron acquisition during intracellular growth of the plague bacterium...

..We propose that HmsT and HmsP together control the amount of biofilm produced in Y. pestis. Degradation of HmsT at 37 degrees C may be a critical factor in controlling the temperature-dependent expression of the Hms biofilm...

..Finally, we have shown that polyamines play a role in bubonic plague...

..pestis CO92 (epidemic orientalis biovar). Experimental studies failed to identify a role for hemin uptake systems in the virulence of pneumonic plague and suggest that Y. pestis CO92 does not make a siderophore other than Ybt...

..In contrast, cells containing a single amino acid substitution (S2908A) in the terminal thioesterase domain of HMWP2 failed to exhibit any ybt regulatory defects but did not elaborate extracellular Ybt under iron-deficient conditions...

..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...

..pestis cells carrying adrA under the control of an arabinose-inducible promoter produced substantial biofilms in the presence of arabinose. Finally, we demonstrate that HmsT is involved in the synthesis of cyclic di-GMP...

..The Y. pestis lacZ promoter was not regulated by isopropylthiogalactoside or glucose. Finally, uptake of lactose by Y. pestis may be impaired...

..pestis from the ancestral Yersinia pseudotuberculosis was a significant reduction in the complexity of its c-di-GMP signalling network likely resulting from the different disease cycles of these human pathogens...

..Finally, using a polar hmsH : : mini-kan mutant, we demonstrated that biofilm development is not important for the pathogenesis of bubonic or pneumonic plague in mice...

..Here we demonstrate that hemin uptake and iron utilization from Ybt are TonB dependent. However, the Yfe iron and manganese transport system does not require TonB...

..Biochemical analyses confirmed some of these protein-protein interactions. Our results indicate that synthesis and regulation of the Y. pestis biofilm EPS occurs in the cytoplasm by a proposed Hms enzymatic complex...

..Finally, protein-protein interactions and the cytoplasmic location of the enzymatic domains of HmsT and HmsP are evaluated...

..Two-dimensional gel electrophoresis revealed altered levels of protein expression in a Y. pestis triple QS mutant at 26 degrees C and 37 degrees C...

..However, HmsT at 37 degrees C is sensitive to degradation by Lon and/or ClpPX. Thus, the stability of HmsH, HmsR, and HmsT proteins likely plays a role in temperature regulation of the Hms+ phenotype of Y. pestis...

..pestis and indicate that there is a hierarchy of iron transporters, with Ybt being most effective and Yiu being the least effective of those systems which have been characterized...

..Mutations in the fhu operon, but not in iutA, affected the ability of KIM6 to use ferrichrome. This demonstrates that Y. pestis uses both ferrichrome and aerobactin, but has lost the ability to synthesize aerobactin...

..While the proposed function of EAL-domain proteins is to linearize c-di-GMP, this is a direct demonstration of the required phosphodiesterase activity of a purified EAL-domain protein...

..pestis adherence, invasion, and virulence. We found that loss of yadBC caused a modest loss of invasiveness for epithelioid cells and a large decrease in virulence for bubonic plague but not for pneumonic plague in mice...

..Finally, a Delta pgm mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb pgm locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague...

..While these compounds are not biologically relevant to normal Ybt regulation, a comparison of the structures of Ybt and other signalling molecules will help in determining the chemical structures recognized as a Ybt signal...

..Strains lacking either the chromosomal pgm locus or the Lcr plasmid can be safely studied under BSL-2 conditions and are exempt from Select Agent regulations in the U.S...

..Chemical complementation of the double mutant and recovery of the biofilm defect were only observed with the polyamine putrescine...

..To our knowledge this is the first report of the ferric crystal structure of 5-member heterocycle siderophore...

..Our data also indicate that Gpm expression and, therefore, glycolysis would not be abrogated when T. pallidum encounters high Zn2+ levels...

..pestis life cycle were strongly altered in abundance. This included a putative nitrate/sulfonate/bicarbonate-specific SBP (Y1004), encoded by the virulence-associated plasmid pMT1 and increased in abundance at 37 degrees C...

..These data demonstrate that intracellular Y. pestis can evade killing by macrophages that are exposed to IFN-gamma and identify a potential virulence gene encoded in the pgm locus that is required for this activity...

..In KIM-specific islands, new genes encode candidate pathogenicity proteins, including iron transport systems, putative adhesins, toxins, and fimbriae...

..This finding should facilitate the design and development of a new generation of vaccines against Y. pestis...

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..Our studies will also provide insights into the role of Ybt and Yfe in the pathogenesis of plague and other disease-causing organisms and into the general importance of iron acquisition in bacterial disease processes. ..

..Understanding how the bacterium makes this siderophore and how its production is regulated may eventually lead to the development of either a vaccine or new drugs against plague and other bacterial diseases. ..

..Understanding how the plague bacterium makes biofilm may eventually lead to ways to prevent biofilm formation in other bacterial pathogens. ..

..Understanding how the bacterium makes this siderophore and how its production is regulated may eventually lead to the development of either a vaccine or new drugs against plague and other bacterial diseases. ..

..Understanding how the plague bacterium makes biofilm may eventually lead to ways to prevent biofilm formation in other bacterial pathogens. ..

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..The Hmu mechanism of hemin- compound utilization will be investigated and its role in the infectious process in mammals and fleas determined...

..The Hmu mechanism of hemin- compound utilization will be investigated and its role in the infectious process in mammals and fleas determined. ..

..Understanding how the bacterium makes this siderophore and how its production is regulated may eventually lead to the development of either a vaccine or new drugs against plague and other bacterial diseases. ..