Modulation of Hexa-Acyl Pyrophosphate Lipid A Population underEscherichia coliPhosphate (Pho) Regulon Activation
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ABSTRACTEnvironmental 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 apstmutation results in virulence attenuation in extraintestinal pathogenicEscherichia coli(ExPEC) strains. Our results indicate that the bacterial cell surface of thepstmutants is altered. In this study, we show thatpstmutants 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 inpstmutants. Among differentially expressed genes in thepstmutant,lpxTcoding 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.
