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

Abstract

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.

Antibiotic resistance genes in an urban river as impacted by bacterial community and physicochemical parameters

“…2), which contained some pathogenic members (e.g., Burkholderia mallei responsible for glanders disease that occurs in horses and related animals, Burkholderia pseudomallei a causative agent of melioidosis, Burkholderia cepacia an important pathogen for pulmonary infections in humans with cystic fibrosis) (Woods and Sokol 2006;Djordjevic et al 2013). These findings are consistent with site A1 being the furthest upstream site that is closest to areas with animal husbandry and sites B3 and C1 being in the urban environment and subject to receiving waters from hospital waste and non-treated sewage.…”

Understanding the contribution of environmental factors in the spread of antimicrobial resistance

“…It is believed that the origins of antibiotic resistance genes lies with environmental bacteria that produce and release antibacterial to influence microbial populations with which they compete for nutrients [11]. This is in keeping with the discovery of a wide spectrum of antibiotic resistance genes (for e.g.…”

“…However, it is believed that this naturally occurring resistance can also play a role in the development of acquired resistance; and that both types of resistance can be transmitted horizontally or vertically [10,12]. It is now relatively well understood at the molecular level, that the same gene can be identified in very unrelated pathogens in humans, clinical settings, as well as among bacteria which grow in agricultural context, meat animals and companion animals; suggesting that ABR grows and is context independent [11]. Resistance however can be accelerated by the selective pressure due to frequent and widespread antibiotic usage [4].…”

“…Many studies have described antibiotic resistance genes as part of selftransferable plasmids or of transposable elements, with evidence of genetic transfer occurring between both related and unrelated bacteria [32,36]. It has been postulated that some organisms produce and release antibiotics into their environment to influence and control competing bacteria [11]. This occurs when some of the naturally occurring antibiotic resistance genes becomes captured by a mobile genetic element like an integron, transposon, phage, plasmid, or chromosomal island, which then plays a key role in the introduction of natural resistance genes into clinically relevant bacterial species from environmental sources (for e.g.…”

First description of food-borne Salmonella enterica resistance regions R1 and R3 associated with IS26 elements

“…[5,6,18], both in plasmids and in chromosomal genomic islands [19,20]. In this study, we described three different chromosomal regions containing antibiotic or mercury resistance genes that are flanked by, and eventually interspersed with, copies of IS26, including the new R3.…”