Mobile elements, zoonotic pathogens and commensal bacteria: conduits for the delivery of resistance genes into humans, production animals and soil microbiota.

Multiple antibiotic resistant pathogens represent a major clinical challenge in both human and veterinary context. It is now well-understood that the genes that encode resistance are context independent. That is, the same gene is commonly present in otherwise very disparate pathogens in both humans and production and companion animals, and among bacteria that proliferate in an agricultural context. This can be true even for pathogenic species or clonal types that are otherwise confined to a single host or ecological niche. It therefore follows that mechanisms of gene flow must exist to move genes from one part of the microbial biosphere to another. It is widely accepted that lateral (or horizontal) gene transfer (L(H)GT) drives this gene flow. LGT is relatively well-understood mechanistically but much of this knowledge is derived from a reductionist perspective. We believe that this is impeding our ability to deal with the medical ramifications of LGT. Resistance genes and the genetic scaffolds that mobilize them in multiply drug resistant bacteria of clinical significance are likely to have their origins in completely unrelated parts of the microbial biosphere. Resistance genes are increasingly polluting the microbial biosphere by contaminating environmental niches where previously they were not detected. More attention needs to be paid to the way that humans have, through the widespread application of antibiotics, selected for combinations of mobile elements that enhance the flow of resistance genes between remotely linked parts of the microbial biosphere. Attention also needs to be paid to those bacteria that link human and animal ecosystems. We argue that multiply antibiotic resistant commensal bacteria are especially important in this regard. More generally, the post genomics era offers the opportunity for understanding how resistance genes are mobilized from a one health perspective. In the long term, this holistic approach offers the best opportunity to better manage what is an enormous problem to humans both in terms of health and food security.