ß-lactamase expression induces collateral sensitivity in Escherichia coli.

Major antibiotic groups are losing effectiveness due to the uncontrollable spread of antimicrobial resistance (AMR) genes. Among these, ß-lactam resistance genes -encoding ß-lactamases- stand as the most common resistance mechanism in Enterobacterales due to their frequent association with mobile genetic elements. In this context, novel approaches that counter mobile AMR are urgently needed. Collateral sensitivity (CS) occurs when the acquisition of resistance to one antibiotic increases susceptibility to another antibiotic and can be exploited to eliminate AMR selectively. However, most CS networks described so far emerge as a consequence of chromosomal mutations and cannot be leveraged to tackle mobile AMR. Here, we dissect the CS response elicited by the acquisition of a prevalent antibiotic resistance plasmid to reveal that the expression of the ß-lactamase gene blaOXA-48 induces CS to colistin and azithromycin. We next show that other clinically relevant mobile ß-lactamases produce similar CS responses in multiple, phylogenetically unrelated E. coli strains. Finally, by combining experiments with surveillance data comprising thousands of antibiotic susceptibility tests, we show that ß-lactamase-induced CS is pervasive within Enterobacterales. These results highlight that the physiological side-effects of ß-lactamases can be leveraged therapeutically, paving the way for the rational design of specific therapies to block mobile AMR or at least counteract their effects.

The role of bacterial metabolism in human gut colonization.

Can we anticipate the emergence of the next pandemic antibiotic-resistant bacterial clone? Addressing such an ambitious question relies on our ability to comprehensively understand the ecological and epidemiological factors fostering the evolution of high-risk clones. Among these factors, the ability to persistently colonize and thrive in the human gut is crucial for most high-risk clones. Nonetheless, the causes and mechanisms facilitating successful gut colonization remain obscure. Here, we review recent evidence that suggests that bacterial metabolism plays a pivotal role in determining the ability of high-risk clones to colonize the human gut. Subsequently, we outline novel approaches that enable the exploration of microbial metabolism at an unprecedented scale and level of detail. A thorough understanding of the constraints and opportunities of bacterial metabolism in gut colonization will foster our ability to predict the emergence of high-risk clones and take appropriate containment strategies.

Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae in Fresh Produce.

Fresh vegetables are an essential part of a healthy diet, but microbial contamination of fruits and vegetables is a serious concern to human health, not only for the presence of foodborne pathogens but because they can be a vehicle for the transmission of antibiotic-resistant bacteria. This work aimed to investigate the importance of fresh produce in the transmission of extended-spectrum ß-lactamases (ESBL)-producing Enterobacteriaceae. A total of 174 samples of vegetables (117) and farm environment (57) were analysed to determine enterobacterial contamination and presence of ESBL-producing Enterobacteriaceae. Enterobacterial counts above the detection limit were found in 82.9% vegetable samples and 36.8% environmental samples. The average count was 4.2 log cfu/g or mL, with a maximum value of 6.2 log cfu/g in a parsley sample. Leafy vegetables showed statistically significant higher mean counts than other vegetables. A total of 15 ESBL-producing isolates were obtained from vegetables (14) and water (1) samples and were identified as Serratia fonticola (11) and Rahnella aquatilis (4). Five isolates of S. fonticola were considered multi-drug resistant. Even though their implication in human infections is rare, they can become an environmental reservoir of antibiotic-resistance genes that can be further disseminated along the food chain.