The phosphoethanolamine transferase PetL of Pasteurella multocidais associated with colistin resistance

Abstract

The rapid emergence and spread of colistin-resistant gram-negative bacteria has raised worldwide public health concerns, and phosphoethanolamine (PEtn) transferase modification-mediated colistin resistance has been widely documented in multiple gram-negative bacterial species. However, whether such a mechanism exists in the zoonotic pathogen Pasteurella multocidais still unknown. Recently, a novel PEtn transferase, PetL, was identified in P. multocida, but whether it is associated with colistin resistance remains to be elucidated. In this study, we found that PetL in P. multocida(PetL^PM) exhibited structural characteristics similar to those of the mobile-colistin-resistant (MCR) protein and the PEtn transferase characterized in Neisseria meningitidis.The transformation of petL^PM into E. colior K. pneumoniaechanged the phenotype of several tested strains from colistin sensitive to colistin resistant. Deletion of this gene decreased the colistin minimum inhibitory concentration (MIC) of P. multocida by 64-fold. Our extensive analysis by MALDI-TOF-MS demonstrated that PetL^PM participated in the modification of bacterial lipopolysaccharide (LPS)-lipid A. Deletion of petL^PM led to an increase in membrane charge but a decrease in cell-surface hydrophobicity and cell permeability in P. multocida. The present study is the first to report the presence of PEtn transferase-mediated colistin resistance in the zoonotic pathogen P. multocida.

Keywords

Antimicrobial resistance / Colistin / Pasteurella multocida / Phosphoethanolamine transferase / Lipid A modification

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Funding

Hubei Provincial Natural Science Foundation of China(2023AFA094); Yingzi Tech & Huazhong Agricultural University Intelligent Research Institute of Food Health(IRIFH202209); Fundamental Research Funds for the Central Universities(2662023PY005)