Polymyxins B and E (colistin) exert a bactericidal effect on the gram-negative bacterial cell wall, causing permeability changes in the cytoplasmic membrane, leading to cell death. Their use was substantially decreased in clinical practice from the 1970s to 2000s due to their significant nephrotoxicity and neurotoxicity compared to the newly introduced antibiotics. The increasing prevalence of ...

Klebsiella pneumoniae is an important cause of multidrug-resistant infections worldwide. Recent studies highlight the emergence of multidrug-resistant K. pneumoniae strains which show resistance to colistin, a last-line antibiotic, arising from mutational inactivation of the mgrB regulatory gene. However, the precise molecular resistance mechanisms of mgrB-associated colistin resistance and its...

Polymyxins are cationic lipopeptide antibiotics active against many species of Gram-negative bacteria. We sequenced the gene cluster for polymyxin biosynthesis from Paenibacillus polymyxa PKB1. The 40.8 kb gene cluster comprises three nonribosomal peptide synthetase-encoding genes and two ABC transporter-like genes. Disruption of a peptide synthetase gene abolished all antibiotic production, wh...

A surveillance study to identify patients from the community with Escherichia coli resistant to broad-spectrum cephalosporins discovered two isolates that were also resistant to polymyxin B and colistin. One isolate from a patient in the community and a second from a patient who received multiple courses of polymyxin B also possessed a CTX-M-15 enzyme. Resistance to cationic peptides in E. coli...

The inactivation of the mgrB gene, which encodes a negative-feedback regulator of the PhoPQ signaling system, was recently shown to be a common mutational mechanism responsible for acquired polymyxin resistance among carbapenemase-producing Klebsiella pneumoniae strains from clinical sources. In this work, we show that mgrB mutants can easily be selected in vitro from different K. pneumoniae li...

Previously, we showed that microbial susceptibility to antimicrobials in concentrations non-toxic for human cells in culture could be tested using the wet disc topical antimicrobial assay. In this report, wet disc assay and agar well diffusion assay results were compared testing the susceptibility of Ps. aeruginosa isolates from burn patients to concentrations of Polymyxin B non-toxic for cultu...

One of the drawbacks of the "tube dilution" method for the assay of antibiotics in human serum has been illustrated by utilizing serum-sensitive and serum-resistant strains of Escherichia coli. In the case of serum-sensitive strains, it was found that fresh serum alone may account for the same degree of inhibition and thus yield minimal inhibitory concentrations identical to those obtained with...