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Analogue synthesis reveals decoupling of antibiofilm and β‐lactam potentiation activities of a lead 2‐aminoimidazole adjuvant against Mycobacterium smegmatis
Author(s) -
Martin Sara E.,
Nguyen Catherine M.,
Basaraba Randall J.,
Melander Christian
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13208
Subject(s) - mycobacterium smegmatis , biofilm , antibiotics , microbiology and biotechnology , mycobacterium tuberculosis , multidrug tolerance , carbenicillin , chemistry , ampicillin , bacteria , pharmacology , tuberculosis , biology , medicine , pathology , genetics
Biofilm formation is one of the many mechanisms bacteria utilize to survive antibiotic treatment. It has been demonstrated that when Mycobacterium tuberculosis exists in a biofilm in vitro , it expresses phenotypic resistance to antimicrobial drugs. As the in vivo survival of M. tuberculosis following drug treatment is potentially linked to a biofilm‐like expression of drug tolerance, it is hypothesized that biofilm dispersion should increase antibiotic susceptibility and reduce the duration of the current antibiotic treatment regimen. Previously, we have identified a 2‐aminoimidazole (2‐ AI ) compound capable of dispersing and inhibiting M. tuberculosis and M. smegmatis biofilms in vitro. Additionally, this compound potentiated the activity of carbenicillin against M. tuberculosis and, to a lesser degree, M. smegmatis . Here, we describe a SAR study on this compound evaluating each derivative for biofilm dispersion and β‐lactam potentiation capabilities against M. smegmatis . This study identified a compound that improved upon the biofilm dispersion capabilities of the lead compound. Interestingly, a different compound was identified with an increased ability to potentiate a subset of β‐lactam antibiotics. These compounds indicate that biofilm dispersion and potentiation capabilities may not be associated.