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

• Published in: Microbiology (Society for General Microbiology) Vol. 145; no. 1; pp. 197 - 209
• Main Authors: LillardJr, James W, Bearden, Scott W, Fetherston, Jacqueline D, Perry, Robert D
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.01.1999; Society for General Microbiology
• Subjects: Animals; Bacterial Adhesion; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - physiology; Bacteriology; Biological and medical sciences; Chlorides; Escherichia coli - genetics; Escherichia coli - growth & development; Escherichia coli - metabolism; Ferric Compounds - metabolism; Fundamental and applied biological sciences. Psychology; HeLa Cells; Hemin - metabolism; Humans; Hydrogen Peroxide - pharmacology; Iron Chelating Agents - pharmacology; Lethal Dose 50; Mice; Microbiology; Mutation; Neutrophils - immunology; Neutrophils - metabolism; Nitric Oxide - metabolism; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Phenotype; Plague - microbiology; Reactive Oxygen Species - metabolism; Superoxides - metabolism; Temperature; Virulence; Yersinia pestis; Yersinia pestis - drug effects; Yersinia pestis - genetics; Yersinia pestis - metabolism; Yersinia pestis - pathogenicity; Human; Oxidative stress; Nutrition; Host agent relation; Iron; In vitro; Hela cell line; Survival; Yersinia pestis; Pathogenicity; Resistance; Hemin; Bacteria; Epithelial cell; Neutrophil; Enterobacteriaceae
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/13500872-145-1-197

University of Kentucky, Department of Microbiology and Immunology, MS415 Medical Center, Lexington, Kentucky 40536-0084, USA Author for correspondence: Robert D. Perry. Tel: +1 606 323 6341. Fax: +1 606 257 8994. e-mail: rperry@pop.uky.edu ABSTRACT Summary: The haemin storage (Hms + ) phenotype of Yersinia pestis enables this bacillus to form greenish/brown or red colonies on haemin or Congo Red agar plates, respectively, at 26 but not 37 °C. Escherichia coli strains that contain mutations in genes essential for siderophore biosynthesis, porphyrin generation and/or haemin transport remain unable to utilize exogenous haemin as a nutritional iron or porphyrin source when transformed with the cloned Y. pestis hmsHFRS locus. Further physiological analysis of the Hms + phenotype of Y. pestis strain KIM6+ suggests that the haemin and inorganic iron stored by the Hms system was not used nutritionally under subsequent iron-deficient conditions. In vitro analysis of the bactericidal effects of hydrogen peroxide, superoxide and nitric oxide showed that Hms - Y. pestis cells, in certain cases, were more susceptible than the Hms + parent cells to these reactive oxygen species at 26 and/or 37 °C. In adherence assays, a higher percentage of Hms + cells were associated with HeLa cells and normal human neutrophils, compared to Hms - cells. However, the Hms + phenotype did not provide any additional protection against the killing effects of neutrophils. Finally, LD 50 analysis in subcutaneously infected mice showed that an Hms - strain was slightly more virulent than Hms + , indicating that the Hms phenotype is not essential for the pathogenesis of bubonic plague in mammals. Keywords: HeLa cells, haemin binding, resistance to reactive oxygen species, neutrophils Present address: University of Alabama at Birmingham, Immunobiology Vaccine Center, 770 BBRB, 845 19th St So., Birmingham, AL 35294-2170, USA.