Modulation of hexa-acyl pyrophosphate lipid A population under Escherichia coli phosphate (Pho) regulon activation.
Environmental phosphate is an important signal for microorganism gene regulation, and it has recently been shown to trigger some key bacterial virulence mechanisms. In many bacteria, the Pho regulon is the major circuit involved in adaptation to phosphate limitation. The Pho regulon is controlled jointly by the two-component regulatory system PhoR/PhoB and by the phosphate-specific transport (Pst) system, which both belong to the Pho regulon. We showed that a pst mutation results in virulence attenuation in extraintestinal pathogenic Escherichia coli (ExPEC) strains. Our results indicate that the bacterial cell surface of the pst mutants is altered. In this study, we show that pst mutants of ExPEC strains display an increased sensitivity to different cationic antimicrobial peptides and vancomycin. Remarkably, the hexa-acylated 1-pyrophosphate form of lipid A is significantly less abundant in pst mutants. Among differentially expressed genes in the pst mutant, lpxT coding for an enzyme that transfers a phosphoryl group to lipid A, forming the 1-diphosphate species, was found to be downregulated. Our results strongly suggest that the Pho regulon is involved in lipid A modifications, which could contribute to bacterial surface perturbations. Since the Pho regulon and the Pst system are conserved in many bacteria, such a lipid A modification mechanism could be widely distributed among gram-negative bacterial species.
Groupe de Recherche sur les Maladies Infectieuses du Porc, Université de Montréal, Faculté de Médecine Vétérinaire, CP 5000, Saint-Hyacinthe, Québec, Canada.
Martin G
MG
Lamarche
Sang-Hyun
SH
Kim
Sébastien
S
Crépin
Michael
M
Mourez
Nicolas
N
Bertrand
Russell E
RE
Bishop
J Daniel
JD
Dubreuil
Josée
J
Harel
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D002473:Cell Wall / Q000737:chemistry; D002855:Chromatography, Thin Layer; D011756:Diphosphates / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D008050:Lipid A / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D015394:Molecular Structure; D020411:Oligonucleotide Array Sequence Analysis; D018085:Regulon; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D011756:Diphosphates; D029968:Escherichia coli Proteins; D008050:Lipid A; D026901:Membrane Transport Proteins; D014640:Vancomycin