Environmental mutagens may be implicated in the emergence of drug-resistant microorganisms

Abstract

The emergence of drug-resistant microorganisms is an important medical and social problem. Drug-resistant microorganisms are thought to grow selectively in the presence of antibiotics. Most clinically isolated drug-resistant microorganisms have mutations in the target genes for the drugs. While any of the many mutagens in the environment may cause such genetic mutations, no reports have yet described whether these mutagens can confer drug resistance to clinically important microorganisms. We investigated how environmental mutagens might be implicated in acquired resistance to antibiotics in clinically important microorganisms, which causes human diseases. We selected mutagens found in the environment, in cigarette smoke, or in drugs, and then exposed Pseudomonas aeruginosa to them. After exposure, the incidence of rifampicin- and ciprofloxacin-resistant P. aeruginosa strains markedly increased, and we found mutations in genes for the antibiotic-target molecule. These mutations were similar to those found in drug-resistant microorganisms isolated from clinical samples. Our findings show that environmental mutagens, and an anticancer drug, are capable of inducing drug-resistant P. aeruginosa similar to strains found in clinical settings.

Wastewater reuse in irrigation: A microbiological perspective on implications in soil fertility and human and environmental health

“…The time elapsed between the emergence of a new resistance gene in clinical settings and its detection in municipal wastewater is frighteningly short (Szczepanowski et al, 2009). For instance, bacteria resistant to last resort antibiotics mainly or exclusively used in hospitals, such as carbapenems resistant Gram-negative bacteria, vancomycin resistant entereococci (VRE), or methicillin resistant Staphylococcus aureus (MRSA) are nowadays detected in municipal wastewater worldwide (Manaia et al, 2012;Rizzo et al, 2013;Baker-Austin et al, 2006;Fluit and Schmitz, 2004;Hernández et al, 1998;Miyahara et al, 2011). The wide contamination of the environment and the food chain with these genetic determinants may represent a public health calamity.…”

Bacterial diversity and antibiotic resistance in water habitats: searching the links with the human microbiome

“…Commonly used arguments to explain the evolutionary success of acquired antibiotic resistance Acquired antibiotic resistance is an emblematic example of biological evolution, driven by two major mechanisms genetic variability (mutation and recombination) and selection (Andersson & Hughes, 2010;Thomas & Nielsen, 2005;Wiedenbeck & Cohan, 2011). Genetic variability results from gene mutation and horizontal gene transfer, in which the latter has more dramatic implications on the physiology and ecology of bacteria (Arber, 2000;Hausner & Wuertz, 1999;Miyahara et al, 2011). On the other hand, antibiotics, even at subinhibitory concentrations, or other micro-pollutants such as heavy metals, contribute for the selection of resistant bacteria (Alonso et al, 2001;Davies et al, 2006;Tello et al, 2012).…”

Antibiotic Resistance of Pathogens Causing Community-Acquired Pneumonia

“…Very recently, however, Miyahara and colleagues investigated the effects of exposure of a rifampicin-and ciprofloxacin-sensitive reference strain of P. aeruginosa to a series of known mutagens on the development of antibiotic resistance. 95 The mutagens selected for investigation were (1) the known alkylating agents, ethyl methanesulfonate (EMS) and N-nitroso-N-methylurea (MNU); (2) benzopyrene (BP) and 1,6-dinitropyrene (1,6-DNP), both products of combustion;…”

“…All were used at mechanistically (induction of point mutations) or environmentally relevant concentrations. 95 The bacteria were exposed to the test mutagens for 24 hours, followed by plating-out and selection of rifampicin-and ciprofloxacin-resistant mutants from which DNA was extracted, amplified by polymerase chain reaction (PCR), sequenced and analyzed for point mutations in target genes, these being (1) 2-poB, the β-subunit of RNA polymerase; (2) gyr A and gyr B, which encode the A and B proteins of DNA gyrase; (3) par C and par E, which encode the A and B subunits of topoisomerase IV; and (4) nfxB and mexR, fluoroquinolone efflux pump regulatory genes.…”