Coming from the Wild: Multidrug Resistant Opportunistic Pathogens Presenting a Primary, Not Human-Linked, Environmental Habitat

Abstract

The use and misuse of antibiotics have made antibiotic-resistant bacteria widespread nowadays, constituting one of the most relevant challenges for human health at present. Among these bacteria, opportunistic pathogens with an environmental, non-clinical, primary habitat stand as an increasing matter of concern at hospitals. These organisms usually present low susceptibility to antibiotics currently used for therapy. They are also proficient in acquiring increased resistance levels, a situation that limits the therapeutic options for treating the infections they cause. In this article, we analyse the most predominant opportunistic pathogens with an environmental origin, focusing on the mechanisms of antibiotic resistance they present. Further, we discuss the functions, beyond antibiotic resistance, that these determinants may have in the natural ecosystems that these bacteria usually colonize. Given the capacity of these organisms for colonizing different habitats, from clinical settings to natural environments, and for infecting different hosts, from plants to humans, deciphering their population structure, their mechanisms of resistance and the role that these mechanisms may play in natural ecosystems is of relevance for understanding the dissemination of antibiotic resistance under a One-Health point of view.

Keywords: Acinetobacter baumannii; Aeromonas; Burkholderia cepacia; MDR; One-Health; Pseudomonas aeruginosa; Shewanella; Stenotrophomonas maltophilia; environmental bacteria; intrinsic resistance; opportunistic pathogens.

Figure 1

Schematic representation of the main elements involved in intrinsic and acquired antibiotic resistance in Pseudomonas aeruginosa. P. aeruginosa possesses a remarkable intrinsic resistance to antibiotics caused, among other factors, by the production of antibiotic-modifying enzymes (e.g., β-lactamase AmpC), low outer membrane permeability and a great amount of multidrug resistance (MDR) efflux pumps like MexAB-OprM. Antibiotic resistance level may increase by chromosomal mutations in genes encoding negative regulators of the above-described intrinsic resistance determinants, such as genetic modifications within mexR or ampR, which boost the expression of mexAB-oprM and ampC, respectively. The modification of the antibiotic target is also a frequent mechanism for acquiring antibiotic resistance in P. aeruginosa, as the increased resistance to quinolones by mutations in gyrases encoded by gyrA or gyrB. Alternatively, this bacterium is also able to acquire novel ARGs, which are located in mobile elements, such as plasmids or integrative and conjugative elements (ICEs). It has been stated that bacteriophages might also be involved in the acquisition of ARGs, but the role of these genetic elements in the spread of resistance in P. aeruginosa is not yet fully understood.