The antibiotic resistance “mobilome”: searching for the link between environment and clinic

Abstract

Antibiotic resistance is an ancient problem, owing to the co-evolution of antibiotic-producing and target organisms in the soil and other environments over millennia. The environmental “resistome” is the collection of all genes that directly or indirectly contribute to antibiotic resistance. Many of these resistance determinants originate in antibiotic-producing organisms (where they serve to mediate self-immunity), while others become resistance determinants only when mobilized and over-expressed in non-native hosts (like plasmid-encoded β-lactamases). The modern environmental resistome is under selective pressure from human activities such as agriculture, which may influence the composition of the local resistome and lead to gene transfer events. Beyond the environment, we are challenged in the clinic by the rise in both frequency and diversity of antibiotic resistant pathogens. We assume that clinical resistance originated in the environment, but few examples of direct gene exchange between the environmental resistome and the clinical resistome have been documented. Strong evidence exists to suggest that clinical aminoglycoside and vancomycin resistance enzymes, the extended-spectrum β-lactamase CTX-M and the quinolone resistance gene qnr have direct links to the environmental resistome. In this review, we highlight recent advances in our understanding of horizontal gene transfer of antibiotic resistance genes from the environment to the clinic. Improvements in sequencing technologies coupled with functional metagenomic studies have revealed previously underappreciated diversity in the environmental resistome, and also established novel genetic links to the clinic. Understanding mechanisms of gene exchange becomes vital in controlling the future dissemination of antibiotic resistance.

Co-occurrence of antibiotic and metal resistance genes revealed in complete genome collection

“…In contrast, a non-significant clustering between pathogens and non-pathogens was observed, suggesting that the dissemination of MRGassociated ARG was frequent enough to blur the resistome boundaries between pathogens and nonpathogens. In accordance with previous conclusion, under widespread antibiotic pressure, acquiring favorable genes, such as ARGs, from those non-pathogenic bacteria has markedly accelerated adaptation in pathogens (Perry and Wright, 2013).…”

“…Therefore, the mobility of both ARGs and MRGs within the genomes of different habitats and pathogenicities was investigated in this study in terms of the nearest distance from MGEs (Figure 5a). The distances of both the nearest ARGs and MRGs from the MGEs were much closer in bacteria from pathogen species and human habitat, reflecting the previous reported substantial capacity to develop resistance genes on MGEs in human pathogens (Perry and Wright, 2013;Gillings et al, 2015;Wales and Davies, 2015). Indeed, equipped on the proper transfer machinery, the efficient vehicles in gene shuffling, resistance gene dissemination can markedly be enhanced, benefiting the bacterial communities under environmental stress (Martinez et al, 2015;Soucy et al, 2015).…”

“…Additionally, it has long been established that the ARGs harbored in environmental compartments alone could act as a potential reservoir for transfer to human pathogens (Martinez, 2008;Forsberg et al, 2012;Perry and Wright, 2013), which might also be true for the coupled closest ARG-MRG pairs (the nearest ARG for each MRG, hereafter referred to as ARG-MRG) owing to their physical genetic linkages. Therefore, by examining ARG-MRG coupling profile, we were prompted to ascertain whether there is a significant genome grouping pattern by ecologies.…”

Single-Cell Analyses Revealed Transfer Ranges of IncP-1, IncP-7, and IncP-9 Plasmids in a Soil Bacterial Community

“…On the other hand, plasmids have a role in the commensal reservoir of antibiotic resistance genes among bacteria causing serious clinical problems (55). Therefore, information on the actual transfer ranges of plasmids in a microbial community is undoubtedly important, not only for an understanding of the dynamics of plasmids in nature and their ecological effects as vehicles of environmental genes but also for applying the plasmid tool for developing novel abilities or modifying functions in a microbial community.…”

Mechanisms of antibiotic resistance

“…The presence of antibiotic resistance genes in the aquatic environment is also demonstrated by Fahrenfeld et al (2013) and Suzuki et al (2013). To address the key issue concerning the role of environmental resistance gene reservoir in the emergence of clinically important resistant pathogens, Perry and Wright (2013) reviewed recent works suggesting genetic exchange between the environmental and clinical resistomes. Communityacquired methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major cause of disease in the general population.…”