Biology subjects

Avison, M.

Publications and source records attributed to Avison, M..

3 recordsLinked to original sources

bioRxiv2019

Resistance to aztreonam, in combination with a bicyclic boronate β-lactamase inhibitor in Escherichia coli identified following mixed culture selection

Using mixed culture selection, we show how reduced envelope permeability, reduced target-site affinity, and increased {beta}-lactamase production layer to confer aztreonam/{beta}-lactamase inhibitor resistance in Escherichia coli. We report a clinical isolate producing CTX-M-15 and CMY-4, lacking OmpF, and carrying a PBP3 mutation. It is resistant to aztreonam plus the inhibitors avibactam, relebactam and vaborbactam. Mobilisation of blaSHV-12 into this isolate generated a derivative additionally resistant to aztreonam plus the bicyclic boronate inhibitors 2 and taniborbactam.

microbiology↗

bioRxiv2019

TonB dependent uptake of β-lactam antibiotics in the opportunistic human pathogen Stenotrophomonas maltophilia.

The {beta}-lactam antibiotic ceftazidime is one of only a handful of drugs with proven clinical efficacy against the opportunistic human pathogen Stenotrophomonas maltophilia, Here, we show that mutations in the energy transducer TonB, encoded by smlt0009 in S. maltophilia, confer ceftazidime resistance. This breaks the dogma that {beta}-lactams enter Gram-negative bacteria only by passive diffusion through outer membrane porins. By confirming cross-resistance of Smlt0009 mutants with a siderophore-conjugated lactivicin antibiotic, we reveal that attempts to improve penetration of antimicrobials into Gram negative bacteria by conjugating them with TonB substrates is likely to select {beta}-lactam resistance in S. maltophilia, increasing its clinical threat. Furthermore, we show that S. maltophilia clinical isolates that have an Smlt0009 mutation already exist. Remarkably, therefore, {beta}-lactam use is already eroding the potential utility of currently experimental siderophore-conjugated antimicrobials against this species.

microbiology↗

bioRxiv2018

Synonymous lysine codon usage modification in a mobile antibiotic resistance gene similarly alters protein production in bacterial species with divergent lysine codon usage biases because it removes a duplicate AAA lysine codon.

The mobile antibiotic resistance gene blaIMP-1 is clinically important and has a synonymous AAA:AAG lysine codon usage bias of 73:27. This bias is like that seen in experimentally determined highly expressed genes in Escherichia coli and Acinetobacter baumanii, but quite different from that seen in Pseudomonas aeruginosa (26:74 AAA:AAG). Here we show that, paradoxically, shifting the AAA:AAG lysine codon bias to 8:92 in blaIMP-1 expressed from a natural promoter results in significantly more IMP-1 production in all three species. Sequential site directed mutagenesis revealed that increased IMP-1 production occurs following removal of an AAA,AAA double lysine codon and that otherwise, lysine codon usage had no observable impact on IMP-1 production. We conclude that ribosomal slippage at this poly-adenosine region reduces efficient translation of IMP-1 and that punctuating the region with guanine reduces ribosomal slippage and increases IMP-1 production.

microbiology↗