Abstract
The cell surface of Gram-negative bacteria usually exhibits a net negative charge mostly conferred by lipopolysaccharides (LPS). This property sensitizes bacterial cells to cationic antimicrobial peptides, such as polymyxin B, by favoring their binding to the cell surface. Gram-negative bacteria can modify their surface to counteract these compounds such as the decoration of their LPS by positively charged groups. For example, in Escherichia coli and Salmonella, EptA and ArnT add amine-containing groups to the lipid A moiety. In contrast, LpxT enhances the net negative charge by catalyzing the synthesis of tri-phosphorylated lipid A, whose function is yet unknown. Here, we report that E. coli has the intrinsic ability to resist polymyxin B upon the simultaneous activation of the two component regulatory systems PhoPQ and PmrAB by intricate environmental cues. Among many LPS modifications, only EptA- and ArnT-dependent decorations were required for polymyxin B resistance. Conversely, the acquisition of polymyxin B resistance compromised the innate resistance of E. coli to deoxycholate, a major component of bile. The inhibition of LpxT by PmrR, under PmrAB-inducing conditions, specifically accounted for the acquired susceptibility to deoxycholate. We also report that the kinetics of intestinal colonization by the E. coli lpxT mutant was impaired as compared to wild-type in a mouse model of infection and that lpxT was upregulated at the temperature of the host. Together, these findings highlight an important function of LpxT and suggest that a tight equilibrium between EptA- and LpxT-dependent decorations, which occur at the same position of lipid A, is critical for the life style of E. coli.
Highlights
The lipopolysaccharide (LPS) constitutes the outermost component of Gram-negative bacteria preventing the entry of a wide variety of noxious compounds such as antibiotics and detergents (Nikaido, 2003)
Bacteria have to cope with various noxious compounds with sometimes opposite chemical properties such as cationic antimicrobial peptides (CAMPs) and bile acids
CAMPs are abundant in nature; some are produced by host innate immune systems to prevent invading pathogens
Summary
The lipopolysaccharide (LPS) constitutes the outermost component of Gram-negative bacteria preventing the entry of a wide variety of noxious compounds such as antibiotics and detergents (Nikaido, 2003). In E. coli cells grown in rich nutrient broth, about one third of the total lipid A presents a diphosphate group at position 1 (Touzé et al, 2008) This modification is catalyzed, at the periplasmic side of the plasma membrane, by LpxT, which transfers a phosphate group from undecaprenyl pyrophosphate (C55-PP) to lipid A releasing undecaprenyl phosphate (C55-P) as a by-product (Touzé et al, 2008). C55-P constitutes the lipid carrier for translocation of subunits of cell-wall polysaccharides (e.g., peptidoglycan, O-antigen) across the plasma membrane It is released as C55-PP during polymers biogenesis on the outer side of the plasma membrane, where LpxT uses it as a substrate and contributes to its essential recycling in a redundant manner with other C55-PP phosphatases (El Ghachi et al, 2005; Manat et al, 2014)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
