Mechanisms and fitness costs of resistance to antimicrobial peptides LL-37, CNY100HL and wheat germ histones.

Antimicrobial peptides (AMPs) represent a potential new class of antimicrobial drugs with potent and broad-spectrum activities. However, knowledge about the mechanisms and rates of resistance development to AMPs and the resulting effects on fitness and cross-resistance is limited. We isolated antimi...

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Autores principales:	Hava Lofton, Maria Pränting, Elisabeth Thulin, Dan I Andersson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e6c9a78ddf345c7b408610504727c48
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spelling	oai:doaj.org-article:9e6c9a78ddf345c7b408610504727c482021-11-18T09:03:34ZMechanisms and fitness costs of resistance to antimicrobial peptides LL-37, CNY100HL and wheat germ histones.1932-620310.1371/journal.pone.0068875https://doaj.org/article/9e6c9a78ddf345c7b408610504727c482013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894360/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Antimicrobial peptides (AMPs) represent a potential new class of antimicrobial drugs with potent and broad-spectrum activities. However, knowledge about the mechanisms and rates of resistance development to AMPs and the resulting effects on fitness and cross-resistance is limited. We isolated antimicrobial peptide (AMP) resistant Salmonella typhimurium LT2 mutants by serially passaging several independent bacterial lineages in progressively increasing concentrations of LL-37, CNY100HL and Wheat Germ Histones. Significant AMP resistance developed in 15/18 independent bacterial lineages. Resistance mutations were identified by whole genome sequencing in two-component signal transduction systems (pmrB and phoP) as well as in the LPS core biosynthesis pathway (waaY, also designated rfaY). In most cases, resistance was associated with a reduced fitness, observed as a decreased growth rate, which was dependent on growth conditions and mutation type. Importantly, mutations in waaY decreased bacterial susceptibility to all tested AMPs and the mutant outcompeted the wild type parental strain at AMP concentrations below the MIC for the wild type. Our data suggests that resistance to antimicrobial peptides can develop rapidly through mechanisms that confer cross-resistance to several AMPs. Importantly, AMP-resistant mutants can have a competitive advantage over the wild type strain at AMP concentrations similar to those found near human epithelial cells. These results suggest that resistant mutants could both be selected de novo and maintained by exposure to our own natural repertoire of defence molecules.Hava LoftonMaria PräntingElisabeth ThulinDan I AnderssonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e68875 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hava Lofton Maria Pränting Elisabeth Thulin Dan I Andersson Mechanisms and fitness costs of resistance to antimicrobial peptides LL-37, CNY100HL and wheat germ histones.
description	Antimicrobial peptides (AMPs) represent a potential new class of antimicrobial drugs with potent and broad-spectrum activities. However, knowledge about the mechanisms and rates of resistance development to AMPs and the resulting effects on fitness and cross-resistance is limited. We isolated antimicrobial peptide (AMP) resistant Salmonella typhimurium LT2 mutants by serially passaging several independent bacterial lineages in progressively increasing concentrations of LL-37, CNY100HL and Wheat Germ Histones. Significant AMP resistance developed in 15/18 independent bacterial lineages. Resistance mutations were identified by whole genome sequencing in two-component signal transduction systems (pmrB and phoP) as well as in the LPS core biosynthesis pathway (waaY, also designated rfaY). In most cases, resistance was associated with a reduced fitness, observed as a decreased growth rate, which was dependent on growth conditions and mutation type. Importantly, mutations in waaY decreased bacterial susceptibility to all tested AMPs and the mutant outcompeted the wild type parental strain at AMP concentrations below the MIC for the wild type. Our data suggests that resistance to antimicrobial peptides can develop rapidly through mechanisms that confer cross-resistance to several AMPs. Importantly, AMP-resistant mutants can have a competitive advantage over the wild type strain at AMP concentrations similar to those found near human epithelial cells. These results suggest that resistant mutants could both be selected de novo and maintained by exposure to our own natural repertoire of defence molecules.
format	article
author	Hava Lofton Maria Pränting Elisabeth Thulin Dan I Andersson
author_facet	Hava Lofton Maria Pränting Elisabeth Thulin Dan I Andersson
author_sort	Hava Lofton
title	Mechanisms and fitness costs of resistance to antimicrobial peptides LL-37, CNY100HL and wheat germ histones.
title_short	Mechanisms and fitness costs of resistance to antimicrobial peptides LL-37, CNY100HL and wheat germ histones.
title_full	Mechanisms and fitness costs of resistance to antimicrobial peptides LL-37, CNY100HL and wheat germ histones.
title_fullStr	Mechanisms and fitness costs of resistance to antimicrobial peptides LL-37, CNY100HL and wheat germ histones.
title_full_unstemmed	Mechanisms and fitness costs of resistance to antimicrobial peptides LL-37, CNY100HL and wheat germ histones.
title_sort	mechanisms and fitness costs of resistance to antimicrobial peptides ll-37, cny100hl and wheat germ histones.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9e6c9a78ddf345c7b408610504727c48
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Mechanisms and fitness costs of resistance to antimicrobial peptides LL-37, CNY100HL and wheat germ histones.

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