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

Autor: Jessica Z. Kubicek-Sutherland, Douglas M. Heithoff, Selvi C. Ersoy, William R. Shimp, John K. House, Jamey D. Marth, Jeffrey W. Smith, Michael J. Mahan
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: EBioMedicine, Vol 2, Iss 9, Pp 1169-1178 (2015)
Druh dokumentu: article
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2015.08.012
Popis: 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.
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