Fitness of Salmonella mutants resistant to antimicrobial peptides
2015 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 70, no 2, 432-440 p.Article in journal (Refereed) Published
Objectives: To examine the effects of mutations in the waaY, phoP and pmrB genes, which confer resistance to antimicrobial peptides (AMPs), on fitness of Salmonella Typhimurium. Methods: Survival during low pH, oxidative stress, stationary-phase incubation, exposure to serum and bile and growth in mice and laboratory media were determined by time-kills, disc inhibition assays, competition experiments and optical density measurements. Results: Individual mutations in the waaY gene (involved in LPS core biosynthesis) and in the phoP and pmrB genes (part of two different two-component regulatory systems, phoPQ and pmrAB) conferred no or minor effects on bacterial survival during stressful in vitro conditions or in mice. In contrast, a waaY-phoP-pmrB triple mutant was compromised under most assay conditions. Conclusions: Results from this study show that AMP resistance can be cost-free, as assessed by several assays that attempt to mimic the conditions a bacterium might encounter within a host. Our findings imply that future therapeutic use of AMPs could select for fit mutants with cross-resistance to human defence peptides and that potential resistance development in response to therapeutic use of AMPs needs to be carefully monitored.
Place, publisher, year, edition, pages
2015. Vol. 70, no 2, 432-440 p.
Salmonella Typhimurium, resistance, bile, serum, mice, pH response, oxidative stress, growth rate
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-249022DOI: 10.1093/jac/dku423ISI: 000350211600011PubMedID: 25362575OAI: oai:DiVA.org:uu-249022DiVA: diva2:807788