Baucheron Sylvie, Chaslus-Dancla Elisabeth, Cloeckaert Axel
Unité BioAgresseurs, Santé et Environnement, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.
J Antimicrob Chemother. 2004 Apr;53(4):657-9. doi: 10.1093/jac/dkh122. Epub 2004 Feb 25.
To study the role of TolC and of parC mutation in high-level fluoroquinolone resistance in clonal clinical strains of Salmonella enterica serotype Typhimurium phage type DT204 (S. Typhimurium DT204).
Deletion of the tolC gene (DeltatolC) was first performed in a susceptible S. Typhimurium DT104 strain lacking target gene mutations involved in fluoroquinolone resistance. P22 transduction was further used to transduce DeltatolC from this strain to a high-level fluoroquinolone-resistant S. Typhimurium DT204 strain carrying several target gene mutations, including one in parC (ciprofloxacin MIC of 32 mg/L).
Deletion of tolC in the high-level fluoroquinolone-resistant S. Typhimurium DT204 strain resulted in the same decrease in resistance levels (16- to 32-fold) as shown previously for an acrB mutant of the same strain, suggesting that AcrAB-TolC is the main efflux system involved in high-level fluoroquinolone resistance of S. Typhimurium DT204 strains. In some S. Typhimurium DT204 DeltatolC transductants, concomitant loss of the parC (Ser-80-->Ile) mutation, located approximately 9.3 kb upstream of tolC, resulted in a further 16- to 32-fold decrease in resistance levels to fluoroquinolones and thus a hypersusceptible phenotype (ciprofloxacin MIC of 0.063 mg/L).
The AcrAB-TolC efflux system, together with multiple target gene mutations, including the parC mutation, appear essential to confer high-level fluoroquinolone resistance in S. Typhimurium DT204.
研究耐碳青霉烯类鲍曼不动杆菌（CRAB）临床分离株中TolC和parC突变在高水平氟喹诺酮耐药中的作用。
首先在一株缺乏参与氟喹诺酮耐药的靶基因突变的敏感鼠伤寒沙门氏菌DT104菌株中进行tolC基因缺失（DeltatolC）。进一步使用P22转导将DeltatolC从该菌株转导至携带多个靶基因突变的高水平氟喹诺酮耐药鼠伤寒沙门氏菌DT204菌株，其中包括parC中的一个突变（环丙沙星MIC为32mg/L）。
在高水平氟喹诺酮耐药的鼠伤寒沙门氏菌DT204菌株中缺失tolC导致耐药水平下降程度与该菌株的acrB突变体相同（16至32倍），这表明AcrAB-TolC是参与鼠伤寒沙门氏菌DT204菌株高水平氟喹诺酮耐药的主要外排系统。在一些鼠伤寒沙门氏菌DT204 DeltatolC转导子中，位于tolC上游约9.3kb处的parC（Ser-80-->Ile）突变同时缺失，导致对氟喹诺酮的耐药水平进一步下降16至32倍，从而呈现超敏表型（环丙沙星MIC为0.063mg/L）。
AcrAB-TolC外排系统以及包括parC突变在内的多个靶基因突变对于赋予鼠伤寒沙门氏菌DT204高水平氟喹诺酮耐药似乎至关重要。
