title: Characterization of late acyltransferase genes of Yersinia pestis and their role in temperature-dependent lipid A variation.
abstract: Yersinia pestis is an important human pathogen that is maintained in flea-rodent enzootic cycles in many parts of the world. During its life cycle, Y. pestis senses host-specific environmental cues such as temperature and regulates gene expression appropriately to adapt to the insect or mammalian host. For example, Y. pestis synthesizes different forms of lipid A when grown at temperatures corresponding to the in vivo environments of the mammalian host and the flea vector. At 37 degrees C, tetra-acylated lipid A is the major form; but at 26 degrees C or below, hexa-acylated lipid A predominates. In this study, we show that the Y. pestis msbB (lpxM) and lpxP homologs encode the acyltransferases that add C12 and C(16:1) groups, respectively, to lipid IV(A) to generate the hexa-acylated form, and that their expression is upregulated at 21 degrees C in vitro and in the flea midgut. A Y. pestis deltamsbB deltalpxP double mutant that did not produce hexa-acylated lipid A was more sensitive to cecropin A, but not to polymyxin B. This mutant was able to infect and block fleas as well as the parental wild-type strain, indicating that the low-temperature-dependent change to hexa-acylated lipid A synthesis is not required for survival in the flea gut.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, Montana 59840, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rebeil
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ernst
authors.forename: Clayton O
authors.initials: CO
authors.lastname: Jarrett
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Adams
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
authors.forename: B Joseph
authors.initials: BJ
authors.lastname: Hinnebusch
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D008050:Lipid A / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011112:Polymyxin B / Q000494:pharmacology; D005423:Siphonaptera / Q000382:microbiology; D013696:Temperature; D015854:Up-Regulation; D015010:Yersinia pestis / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008050:Lipid A; C031161:cecropin A; D000217:Acyltransferases; D011112:Polymyxin B