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Characterization of triclosan-resistant mutants reveals multiple antimicrobial resistance mechanisms in Rhodospirillum rubrum S1H

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Abstract
Antimicrobial resistance mechanisms were identified in 11 spontaneous high-and low-level triclosan resistance (Tcs(r)) mutants of Rhodospirillum rubrum S1H by genotyping complemented with transcriptional analyses, antibiotic resistance screening, and membrane permeability analyses. High-end Tcs(r) (MIC = 8 mg/liter) was the result of a FabI1(G98V) mutation. This point mutation led to an even higher level of Tcs(r) (MIC >= 16 mg/liter) in combination with constitutive upregulation of mexB and mexF efflux pump homologs. Hence, a mechanistic synergy of constitutive efflux pump expression and a FabI1 point mutation could prevent TCS-induced cell permeabilization, which was shown to occur between 4 and 8 mg/liter TCS in the R. rubrum S1H parent strain. Low-level Tcs(r) mutants constitutively upregulated the emrAB, mexAB, and/or mexF homolog. The mutants that overexpressed emrAB also derepressed the micropollutant-upregulated factors mufA1 and mufM. In some cases, low-level Tcs(r) decreased innate resistance to ampicillin and tetracycline, while in others, a triclosan-induced antibiotic cross-resistance was shown for chloramphenicol and carbenicillin. This study showed that the TCS resistance degree is dependent of the initial exposure concentration in Rhodospirillum rubrum S1H and that similar resistance degrees can be the result of different defense mechanisms, which all have distinct antibiotic cross-resistance profiles.
Keywords
FATTY-ACID BIOSYNTHESIS, ENTERICA SEROVAR TYPHIMURIUM, PSEUDOMONAS-AERUGINOSA, ESCHERICHIA-COLI, ANTIBIOTIC-RESISTANCE, SALMONELLA-ENTERICA, CROSS-RESISTANCE, RHODOBACTER-SPHAEROIDES, EFFLUX PUMPS, INTRINSIC RESISTANCE

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Citation

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Chicago
Pycke, Benny, Aurelie Crabbe, Willy Verstraete, and Natalie Leys. 2010. “Characterization of Triclosan-resistant Mutants Reveals Multiple Antimicrobial Resistance Mechanisms in Rhodospirillum Rubrum S1H.” Applied and Environmental Microbiology 76 (10): 3116–3123.
APA
Pycke, B., Crabbe, A., Verstraete, W., & Leys, N. (2010). Characterization of triclosan-resistant mutants reveals multiple antimicrobial resistance mechanisms in Rhodospirillum rubrum S1H. APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 76(10), 3116–3123.
Vancouver
1.
Pycke B, Crabbe A, Verstraete W, Leys N. Characterization of triclosan-resistant mutants reveals multiple antimicrobial resistance mechanisms in Rhodospirillum rubrum S1H. APPLIED AND ENVIRONMENTAL MICROBIOLOGY. 2010;76(10):3116–23.
MLA
Pycke, Benny, Aurelie Crabbe, Willy Verstraete, et al. “Characterization of Triclosan-resistant Mutants Reveals Multiple Antimicrobial Resistance Mechanisms in Rhodospirillum Rubrum S1H.” APPLIED AND ENVIRONMENTAL MICROBIOLOGY 76.10 (2010): 3116–3123. Print.
@article{1086827,
  abstract     = {Antimicrobial resistance mechanisms were identified in 11 spontaneous high-and low-level triclosan resistance (Tcs(r)) mutants of Rhodospirillum rubrum S1H by genotyping complemented with transcriptional analyses, antibiotic resistance screening, and membrane permeability analyses. High-end Tcs(r) (MIC = 8 mg/liter) was the result of a FabI1(G98V) mutation. This point mutation led to an even higher level of Tcs(r) (MIC {\textrangle}= 16 mg/liter) in combination with constitutive upregulation of mexB and mexF efflux pump homologs. Hence, a mechanistic synergy of constitutive efflux pump expression and a FabI1 point mutation could prevent TCS-induced cell permeabilization, which was shown to occur between 4 and 8 mg/liter TCS in the R. rubrum S1H parent strain. Low-level Tcs(r) mutants constitutively upregulated the emrAB, mexAB, and/or mexF homolog. The mutants that overexpressed emrAB also derepressed the micropollutant-upregulated factors mufA1 and mufM. In some cases, low-level Tcs(r) decreased innate resistance to ampicillin and tetracycline, while in others, a triclosan-induced antibiotic cross-resistance was shown for chloramphenicol and carbenicillin. This study showed that the TCS resistance degree is dependent of the initial exposure concentration in Rhodospirillum rubrum S1H and that similar resistance degrees can be the result of different defense mechanisms, which all have distinct antibiotic cross-resistance profiles.},
  author       = {Pycke, Benny and Crabbe, Aurelie and Verstraete, Willy and Leys, Natalie},
  issn         = {0099-2240},
  journal      = {APPLIED AND ENVIRONMENTAL MICROBIOLOGY},
  keyword      = {FATTY-ACID BIOSYNTHESIS,ENTERICA SEROVAR TYPHIMURIUM,PSEUDOMONAS-AERUGINOSA,ESCHERICHIA-COLI,ANTIBIOTIC-RESISTANCE,SALMONELLA-ENTERICA,CROSS-RESISTANCE,RHODOBACTER-SPHAEROIDES,EFFLUX PUMPS,INTRINSIC RESISTANCE},
  language     = {eng},
  number       = {10},
  pages        = {3116--3123},
  title        = {Characterization of triclosan-resistant mutants reveals multiple antimicrobial resistance mechanisms in Rhodospirillum rubrum S1H},
  url          = {http://dx.doi.org/10.1128/AEM.02757-09},
  volume       = {76},
  year         = {2010},
}

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