The MerR-Like Regulator BrlR Impairs Pseudomonas aeruginosa Biofilm Tolerance to Colistin by Repressing PhoPQ

被引:46
作者
Chambers, Jacob R. [1 ]
Sauer, Karin [1 ]
机构
[1] SUNY Binghamton, Dept Biol Sci, Binghamton, NY 13901 USA
基金
美国国家卫生研究院;
关键词
CATIONIC ANTIMICROBIAL PEPTIDES; POLYMYXIN-B; CYSTIC-FIBROSIS; ADAPTIVE RESISTANCE; BACTERIAL BIOFILMS; ESCHERICHIA-COLI; EFFLUX PUMPS; PMRA-PMRB; SYSTEM; OUTER;
D O I
10.1128/JB.00834-13
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
While the MerR-like transcriptional regulator BrlR has been demonstrated to contribute to Pseudomonas aeruginosa biofilm tolerance to antimicrobial agents known as multidrug efflux pump substrates, the role of BrlR in resistance to cationic antimicrobial peptides (CAP), which is based on reduced outer membrane susceptibility, is not known. Here, we demonstrate that inactivation of brlR coincided with increased resistance of P. aeruginosa to colistin, while overexpression of brlR resulted in increased susceptibility. brlR expression correlated with reduced transcript abundances of phoP, phoQ, pmrA, pmrB, and arnC. Inactivation of pmrA and pmrB had no effect on the susceptibility of P. aeruginosa biofilms to colistin, while inactivation of phoP and phoQ rendered biofilms more susceptible than the wild type. The susceptibility phenotype of Delta phoP biofilms to colistin was comparable to that of P. aeruginosa biofilms overexpressing brlR. BrlR was found to directly bind to oprH promoter DNA of the oprH-phoPQ operon. BrlR reciprocally contributed to colistin and tobramycin resistance in P. aeruginosa PAO1 and CF clinical isolates, with overexpression of brlR resulting in increased tobramycin MICs and increased tobramycin resistance but decreased colistin MICs and increased colistin susceptibility. The opposite trend was observed upon brlR inactivation. The difference in susceptibility to colistin and tobramycin was eliminated by combination treatment of biofilms with both antibiotics. Our findings establish BrlR as an unusual member of the MerR family, as it not only functions as a multidrug transport activator, but also acts as a repressor of phoPQ expression, thus suppressing colistin resistance.
引用
收藏
页码:4678 / 4688
页数:11
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