Clinically relevant antibiotic resistance genes are linked to a limited set of taxa within gut microbiome worldwide

Abstract

The acquisition of antimicrobial resistance (AR) genes has rendered important pathogens nearly or fully unresponsive to antibiotics. It has been suggested that pathogens acquire AR traits from the gut microbiota, which collectively serve as a global reservoir for AR genes conferring resistance to all classes of antibiotics. However, only a subset of AR genes confers resistance to clinically relevant antibiotics, and, although these AR gene profiles are well-characterized for common pathogens, less is known about their taxonomic associations and transfer potential within diverse members of the gut microbiota. We examined a collection of 14,850 human metagenomes and 1666 environmental metagenomes from 33 countries, in addition to nearly 600,000 isolate genomes, to gain insight into the global prevalence and taxonomic range of clinically relevant AR genes. We find that several of the most concerning AR genes, such as those encoding the cephalosporinase CTX-M and carbapenemases KPC, IMP, NDM, and VIM, remain taxonomically restricted to Proteobacteria. Even cfiA, the most common carbapenemase gene within the human gut microbiome, remains tightly restricted to Bacteroides, despite being found on a mobilizable plasmid. We confirmed these findings in gut microbiome samples from India, Honduras, Pakistan, and Vietnam, using a high-sensitivity single-cell fusion PCR approach. Focusing on a set of genes encoding carbapenemases and cephalosporinases, thus far restricted to Bacteroides species, we find that few mutations are required for efficacy in a different phylum, raising the question of why these genes have not spread more widely. Overall, these data suggest that globally prevalent, clinically relevant AR genes have not yet established themselves across diverse commensal gut microbiota.

Genomic and functional analysis of the mucinolytic species Clostridium celatum, Clostridium tertium, and Paraclostridium bifermentans

“…Notably, the species C. tertium can exhibit resistance against various other antibiotics, including cephalosporins ( Leegaard et al, 2005 ; Sutton et al, 2017 ). Albeit the presence of a number of genes encoding efflux pumps and other putative antibiotic-resistance genetic determinants in C. celatum WC0700, P. bifermentans WC0705, and C. tertium WC0709, it is noteworthy that only a subset of antibiotic resistance genes confers resistance to clinically relevant antibiotics ( Diebold et al, 2023 ).…”

Long-term beneficial effect of faecal microbiota transplantation on colonisation of multidrug-resistant bacteria and resistome abundance in patients with recurrent Clostridioides difficile infection

“…These improved culturomics methods from diverse environments can in turn help alleviate the biases in genome databases, in which Gram-negative pathogens such as Enterobacterales have been relatively overrepresented. A recent large-scale analysis pointed out that the clinically most relevant ARGs are restricted to particular taxa, most notable Enterobacterales and Bacteroides [ 77 ]. Replacement of antibiotic-resistant bacteria may require introduction of susceptible strains [ 34 ], which, combined with our data, may suggest a role for FMT donors carrying antibiotic-susceptible Enterobacterales.…”

Biomimetic Bacterium-like Particles Loaded with Aggregation-Induced Emission Photosensitizers as Plasma Coatings for Implant-Associated Infections

“…IAIs result in 100,000 deaths each year in the United States of America, resulting in higher healthcare expenses and extra stays in hospitals . The clinical treatments for delayed IAIs include implant replacement, surgical revisions, and long-term use of antibiotics. − Due to the rapid evolution of multidrug-resistant bacteria, higher doses of antibiotics are required to treat IAIs, which cause antimicrobial resistance in such patients. , This will lead to a higher risk of relapse, patient discomfort, and hospital expenses . The systemic administration of antibiotics has proven to be ineffective in patients due to the suboptimal bioavailability of drugs, poor drug penetration, and multidrug resistance in such bacteria .…”

“…5−7 Due to the rapid evolution of multidrug-resistant bacteria, higher doses of antibiotics are required to treat IAIs, which cause antimicrobial resistance in such patients. 8,9 This will lead to a higher risk of relapse, patient discomfort, and hospital expenses. 10 The systemic administration of antibiotics has proven to be ineffective in patients due to the suboptimal bioavailability of drugs, poor drug penetration, and multidrug resistance in such bacteria.…”