Emergence of fluoroquinolone-resistant Propionibacterium acnes caused by amino acid substitutions of DNA gyrase but not DNA topoisomerase IV. (December 2016)

• Record Type: Journal Article
• Authors: Nakase, Keisuke; Sakuma, Yui; Nakaminami, Hidemasa; Noguchi, Norihisa
• Is Part Of: Anaerobe. Volume 42(2016)
• Page Start: 166
• Page End: 171
• Publication Date: 2016-12
• Subjects: Propionibacterium acnes -- Fluoroquinolone resistance -- DNA gyrase -- Amino acid substitution; Anaerobic infections -- Periodicals; Anaerobic bacteria -- Periodicals; Bacterial diseases -- Periodicals; Computer network resources; Anaerobic protozoa -- Periodicals; 579.3
• DOI: 10.1016/j.anaerobe.2016.10.012
• Languages: English
• ISSNs: 1075-9964

Abstract

Abstract: With the aim of elucidating the mechanisms of fluoroquinolones resistance in Propionibacterium acnes, we determined the susceptibility of fluoroquinolones in 211 isolates from patients with acne vulgaris. We identified five isolates (2.4%) with reduced susceptibility to nadifloxacin (minimum inhibitory concentration ≥ 4 μg/ml). Determination of the sequences of the DNA gyrase ( gyrA and gyrB ) and DNA topoisomerase ( parC and parE ) genes showed the amino acid substitutions Ser101Leu and Asp105Gly of GyrA in four and one of the isolates, respectively. In vitro mutation experiments showed that low-level fluoroquinolone-resistant mutants with the Ser101Leu or Asp105Gly substitution in GyrA could be obtained from selection with ciprofloxacin and levofloxacin. The pattern of substitution (Ser101Trp in GyrA) caused by nadifloxacin selection was different from that induced by the other fluoroquinolones. In the isolation of further high-level resistant mutants, acquisition of another amino acid substitution of GyrB in addition to those of GyrA was detected, but there were no substitutions of ParC and ParE. In addition, the mutant prevention concentration and mutation frequency of nadifloxacin were lowest among the tested fluoroquinolones. The growth of the Ser101Trp mutant was lower than that of the other mutants. Our findings suggest that the Ser101Trp mutant of P. acnes emerges rarely and disappears immediately, and the risk for the prevalence of fluoroquinolones-resistant P. acnes differs according to the GyrA mutation type. To our knowledge, this study is the first to demonstrate the mechanisms of resistance to fluoroquinolones in P. acnes . Highlights: GyrA Ser101Leu or Asp105Gly cause fluoroquinolone resistance in P. acnes . GyrA amino acid substitution patterns depend on the selected fluoroquinolones agents. Amino acid substitution was detected in DNA gyrase and not DNA topoisomerase IV. Mutation frequencies and growth rates of resistant mutants differed. Oral fluoroquinolones might contribute to fluoroquinolone resistance in P. acnes.