Identification of EnvC and Its Cognate Amidases as Novel Determinants of Intrinsic Resistance to Cationic Antimicrobial Peptides

Antimicrobial Agents and Chemotherapy
Tamiko OguriHyunwoo Lee

Abstract

Cationic antimicrobial peptides (CAMPs) are an essential part of the innate immune system. Some Gram-negative enteric pathogens, such asSalmonella enterica, show intrinsic resistance to CAMPs. However, the molecular basis of intrinsic resistance is poorly understood, largely due to a lack of information about the genes involved. In this study, using a microarray-based genomic technique, we screened the Keio collection of 3,985Escherichia colimutants for altered susceptibility to human neutrophil peptide 1 (HNP-1) and identifiedenvCandzapBas novel genetic determinants of intrinsic CAMP resistance. In CAMP killing assays, anE. coliΔenvCEcor ΔzapBEcmutant displayed a distinct profile of increased susceptibility to both LL-37 and HNP-1. Both mutants, however, displayed wild-type resistance to polymyxin B and human β-defensin 3 (HBD3), suggesting that the intrinsic resistance mediated by EnvC or ZapB is specific to certain CAMPs. A correspondingSalmonellaΔenvCSemutant showed similarly increased CAMP susceptibility. TheenvCmutants of bothE. coliandS. entericadisplayed increased surface negativity and hydrophobicity, which partly explained the increased CAMP susceptibility. However, the ΔenvCEcmutant, but not the ΔenvCSemutant, was de...Continue Reading

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Citations

Sep 13, 2017·Antimicrobial Agents and Chemotherapy·Anna KnöppelDan I Andersson
Oct 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jonathan CookAllister Crow
Jun 3, 2021·Antibiotics·Kylen E Ridyard, Joerg Overhage

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Methods Mentioned

BETA
gene knockouts
chip
PCR
electrophoresis

Software Mentioned

GraphPad Prism

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