Year: 2024
Type: article
Abstract: (CRAb) is an urgent bacterial threat to public health, with only a few treatment options and a >50% fatality rate. Although several resistance mechanisms are understood, the appearance of these mutations is generally considered stochastic. Recent reports have, however, begun to challenge this assumption. Here, we demonstrate that independent samples of Ab, exposed to different carbapenems with escalating concentrations, show concentration- and carbapenem-dependent trends in β-lactamase-isoform expression. This result, based on the isoforms identified through label-free-quantification LC-MS/MS measurements of cell-free, gel-separated β-lactamases, suggests that the appearance of antibiotic resistance may be somewhat non-stochastic. Specifically, several minor AmpC/ADC β-lactamase-isoforms were found to exhibit both dose- and carbapenem-dependent expression, suggesting the possibility of non-stochastic mutations. Additionally, these also have high sequence similarity to major expressed isoforms, indicating a potential path over which resistance occurred in independent samples. Antibiotic resistance maybe somewhat antibiotic-directed by a hitherto unknown mechanism and further investigation may lead to new strategies for mitigating antibiotic resistance. Teaser: The emergence of antibiotic-resistant β-lactamase proteins from mutations may exhibit patterns based on specific antibiotics.
Source: Scientific Reports
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,590
Awards: A broad-spectrum antimicrobial ointment containing Bi2O3 NPs for skin and soft tissue infections by multidrug-resistant bacteria, G6350843461, G7693085416, G851966567, G9000236014, Rational design and testing of blood-brain-barrier shuttle peptide, Magnetothermal brain stimulation towards the rescue of beta-amyloid pathology
OpenAlex ID: W4405842842