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EBioMedicine. 2015 Aug 11;2(9):1169-78. doi: 10.1016/j.ebiom.2015.08.012. eCollection 2015 Sep.

Host-dependent Induction of Transient Antibiotic Resistance: A Prelude to Treatment Failure.

Author information

1
Dept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
2
Dept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA ; Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA.
3
University of Sydney, Faculty of Veterinary Science, Camden, NSW, Australia.
4
Dept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA ; Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA ; Sanford-Burnham Medical Research Institute, Cancer Research Center, La Jolla, CA 92037, USA.
5
Sanford-Burnham Medical Research Institute, Cancer Research Center, La Jolla, CA 92037, USA.

Abstract

Current antibiotic testing does not include the potential influence of host cell environment on microbial susceptibility and antibiotic resistance, hindering appropriate therapeutic intervention. We devised a strategy to identify the presence of host-pathogen interactions that alter antibiotic efficacy in vivo. Our findings revealed a bacterial mechanism that promotes antibiotic resistance in vivo at concentrations of drug that far exceed dosages determined by standardized antimicrobial testing. This mechanism has escaped prior detection because it is reversible and operates within a subset of host tissues and cells. Bacterial pathogens are thereby protected while their survival promotes the emergence of permanent drug resistance. This host-dependent mechanism of transient antibiotic resistance is applicable to multiple pathogens and has implications for the development of more effective antimicrobial therapies.

KEYWORDS:

Antibiotic resistance; Antibiotic susceptibility testing; Antibiotic-resistant mutants; Antimicrobial therapy; MIC testing; Multidrug-resistant pathogens; Salmonella

PMID:
26501114
PMCID:
PMC4588393
DOI:
10.1016/j.ebiom.2015.08.012
[Indexed for MEDLINE]
Free PMC Article

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