HmsT, a protein essential for expression of the haemin storage (Hms+) phenotype of Yersinia pestis

Abstract

The haemin storage (Hrns) phenotype of Yersinia pestis has been shown to be involved in the blockage of fleas that is required for the transmission of plague from fleas to mammals. Previously, an operon encoding four genes, hmsHFRS, that are essential for the temperature-regulated Hms+ phenotype has been characterized. Here the isolation and characterization of a fifth gene, hmsT, that is essential for this phenotype is described. Conceptual translation of hmsT suggests it encodes a 44.8 kDa protein with a pl of 7.75. The gene for

Bacterial c-di-GMP Is an Immunostimulatory Molecule

“…The cyclic dinucleotide c-di-GMP is now recognized as a widespread intracellular signaling molecule in prokaryotes (2,3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). We have explored the extracellular biological effects of c-di-GMP and its potential use as a therapeutic agent.…”

“…The level of intracellular c-di-GMP in some species is believed to be regulated by the opposing effects of diguanylate cyclases for c-di-GMP synthesis from GTP and c-di-GMP phosphodiesterase for breakdown to 5Ј-GMP and each controlling the level of c-di-GMP in the cell. c-di-GMP has been shown to influence bacterial cell survival, cell differentiation, colonization and biofilm formation, as well as bacteria-host interactions (2,3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Although the role of intracellular c-di-GMP in bacteria is now recognized and is becoming an intense field of research, we have been studying the effect of this microbial molecule in the context of other biological systems and its potential clinical and therapeutic use for the prevention and inhibition of infection and disease (19 -22).…”

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

“…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 . Recent studies have demonstrated Hms-dependent biofilm formation in vitro as well as in fleas and nematodes (Darby et al, 2002;Jarrett et al, 2004;Jones et al, 1999;Kirillina et al, 2004). CR binds basic and neutral polysaccharides while wheat germ agglutinin binds to N-acetylglucosamine, suggesting that the Hms-dependent biofilm contains an exopolysaccharide (EPS) component.…”

“…HmsP, a negative regulator of biofilm formation, is an EAL phosphodiesterase and likely degrades c-di-GMP. Like other glycosyltransferases involved in EPS or cellulose productions, the enzymic activity of HmsR may depend upon c-di-GMP (Bobrov et al, 2005;Hare & McDonough, 1999;Jones et al, 1999;Kirillina et al, 2004;Perry et al, 2004;Simm et al, 2005).…”

“…The 102 kb pgm locus in Y. pestis contains the highpathogenicity island (Ybt) and the hmsHFRS operon encoding four of the six hms genes required for biofilm formation and its regulation. Escherichia coli K-12 pgaABCD (formerly ycdSRQP) encode proteins with similarities (ranging from 34 to 83 %) to Hms proteins and are required for the synthesis of an EPS containing poly-b-1,6-N-acetyl-D-glucosamine (Blattner et al, 1997;Deng et al, 2002;Fetherston et al, 1992;Jones et al, 1999;Lillard et al, 1997;Wang et al, 2004). HmsH and HmsF are outer-membrane proteins while HmsS, HmsR, and HmsT are located in the inner membrane.…”