Abstract
Outer membrane vesicles (OMVs) that are released from Gram-negative pathogenic bacteria can serve as vehicles for the translocation of effectors involved in infectious processes. In this study we have investigated the role of OMVs of the Vibrio cholerae O1 El Tor A1552 strain in resistance to antimicrobial peptides (AMPs). To assess this potential role, we grew V. cholerae with sub-lethal concentrations of Polymyxin B (PmB) or the AMP LL-37 and analyzed the OMVs produced and their effects on AMP resistance. Our results show that growing V. cholerae in the presence of AMPs modifies the protein content of the OMVs. In the presence of PmB, bacteria release OMVs that are larger in size and contain a biofilm-associated extracellular matrix protein (Bap1). We demonstrated that Bap1 binds to the OmpT porin on the OMVs through the LDV domain of OmpT. In addition, OMVs from cultures incubated in presence of PmB also provide better protection for V. cholerae against LL-37 compared to OMVs from V. cholerae cultures grown without AMPs or in presence of LL-37. Using a bap1 mutant we showed that cross-resistance between PmB and LL-37 involved the Bap1 protein, whereby Bap1 on OMVs traps LL-37 with no subsequent degradation of the AMP.
Highlights
V. cholerae is the causative agent of the disease cholera, which remains a significant public health problem, causing large numbers of infections and deaths annually in the world [1]
We provide a mechanistic explanation for cross-resistance between two antimicrobial peptides: Polymyxin B (PmB) and LL-37
We report that bacteria incubated with PmB produce outer membrane vesicles (OMVs) containing high levels of the Bap1 protein
Summary
V. cholerae is the causative agent of the disease cholera, which remains a significant public health problem, causing large numbers of infections and deaths annually in the world [1]. V. cholerae colonizes the surface of the small intestine where it secretes virulence factors [2,3]. Gram-negative bacteria constitutively release lipid bilayer vesicles during normal growth. These outer membrane vesicles (OMVs) range in size from 20–200 nm in diameter. OMVs possess outer membrane proteins, lipopolysaccharide (LPS), phospholipids, and some periplasmic constituents. They have been suggested to play diverse roles in bacterial pathogenesis, including involvement in bacterial communication through OMV-associated signaling molecules, as virulence factors, and in genetic transformation [6,7,8,9,10,11,12]
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