Dataset Information

MexAB-OprM Efflux Pump of Pseudomonas aeruginosa Offers Resistance to Carvacrol: A Herbal Antimicrobial Agent.

ABSTRACT: Carvacrol is a herbal antimicrobial agent with in vitro activity against several bacterial pathogens. However, multidrug resistant strains of Pseudomonas aeruginosa are resistant to herbal antimicrobial compounds including carvacrol. Resistance of P. aeruginosa to carvacrol is not well studied. This study was aimed to identify the gene(s) associated with carvacrol resistance, thus to understand its mechanisms in P. aeruginosa. A herbal drug resistant strain was isolated from a hospital environment. Carvacrol sensitive mutant was generated using transposon mutagenesis. The inactivated gene in the mutant was identified as mexA, which is part of the mexAB-oprM operon. Inactivation of the mexA gene resulted in a >31-fold reduction in MIC of carvacrol, whereas a >80-fold reduction was observed in the presence of drug efflux inhibitor phenylalanine-arginine ?-naphthylamide (PA?N). The parental herbal-resistant strain was completely killed within 3 h of incubation in the presence of carvacrol and PA?N. The mexA inactivation did not affect the resistance to other herbal compounds used. The results demonstrate that resistance to carvacrol in P. aeruginosa is mediated by the MexAB-OprM efflux pump.

SUBMITTER: Pesingi PV

PROVIDER: S-EPMC6877666 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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MexAB-OprM Efflux Pump of Pseudomonas aeruginosa Offers Resistance to Carvacrol: A Herbal Antimicrobial Agent.

Pesingi Prasanna Vadhana PV Singh Bhoj Raj BR Pesingi Pavan Kumar PK Bhardwaj Monika M Singh Shiv Varan SV Kumawat Manoj M Sinha Dharmendra Kumar DK Gandham Ravi Kumar RK

Frontiers in microbiology 20191119

Carvacrol is a herbal antimicrobial agent with in vitro activity against several bacterial pathogens. However, multidrug resistant strains of Pseudomonas aeruginosa are resistant to herbal antimicrobial compounds including carvacrol. Resistance of P. aeruginosa to carvacrol is not well studied. This study was aimed to identify the gene(s) associated with carvacrol resistance, thus to understand its mechanisms in P. aeruginosa. A herbal drug resistant strain was isolat ...[more]

PMID: 31803171

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Project description:The integral inner membrane resistance-nodulation-division (RND) components of three-component RND-membrane fusion protein-outer membrane factor multidrug efflux systems define the substrate selectivity of these efflux systems. To gain a better understanding of what regions of these proteins are important for substrate recognition, a plasmid-borne mexB gene encoding the RND component of the MexAB-OprM multidrug efflux system of Pseudomonas aeruginosa was mutagenized in vitro by using hydroxylamine and mutations compromising the MexB contribution to antibiotic resistance identified in a DeltamexB strain. Of 100 mutants that expressed wild-type levels of MexB and showed increased susceptibility to one or more of carbenicillin, chloramphenicol, nalidixic acid, and novobiocin, the mexB genes of a representative 46 were sequenced, and 19 unique single mutations were identified. While the majority of mutations occurred within the large periplasmic loops between transmembrane segment 1 (TMS-1) and TMS-2 and between TMS-7 and TMS-8 of MexB, mutations were seen in the TMSs and in other periplasmic as well as cytoplasmic loops. By threading the MexB amino acid sequence through the crystal structure of the homologous RND transporter from Escherichia coli, AcrB, a three-dimensional model of a MexB trimer was obtained and the mutations were mapped to it. Unexpectedly, most mutations mapped to regions of MexB predicted to be involved in trimerization or interaction with MexA rather than to regions expected to contribute to substrate recognition. Intragenic second-site suppressor mutations that restored the activity of the G220S mutant version of MexB, which was compromised for resistance to all tested MexAB-OprM antimicrobial substrates, were recovered and mapped to the apparently distal portion of MexB that is implicated in OprM interaction. As the G220S mutation likely impacted trimerization, it appears that either proper assembly of the MexB trimer is necessary for OprM interaction or OprM association with an unstable MexB trimer might stabilize it, thereby restoring activity.

Dataset Information

MexAB-OprM Efflux Pump of Pseudomonas aeruginosa Offers Resistance to Carvacrol: A Herbal Antimicrobial Agent.

Publications

MexAB-OprM Efflux Pump of <i>Pseudomonas aeruginosa</i> Offers Resistance to Carvacrol: A Herbal Antimicrobial Agent.

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