Multiple adaptive routes of Salmonella enterica Typhimurium to biocide and antibiotic exposure

Abstract

BackgroundBiocides and antibiotics are used to eradicate or prevent the growth of microbial species on surfaces (occasionally on catheters), or infected sites, either in combination or sequentially, raising concerns about the development of co-resistance to both antimicrobial types. The effect of such compounds on Salmonella enterica, a major food-borne and zoonotic pathogen, has been analysed in different studies, but only few works evaluated its biological cost, and the overall effects at the genomic and transcriptomic levels associated with diverse phenotypes resulting from biocide exposure, which was the aim of this work.ResultsExposure to triclosan, clorhexidine, benzalkonium, (but not to hypochlorite) resulted in mutants with different phenotypes to a wide range of antimicrobials even unrelated to the selective agent. Most biocide-resistant mutants showed increased susceptibility to compounds acting on the cell wall (β-lactams) or the cell membranes (poly-L-lysine, polymyxin B, colistin or toxic anions). Mutations (SNPs) were found in three intergenic regions and nine genes, which have a role in energy production, amino acids, carbohydrates or lipids metabolism, some of them involved in membrane transport and pathogenicity. Comparative transcriptomics of biocide-resistant mutants showed over-expression of genes encoding efflux pumps (sugE), ribosomal and transcription-related proteins, cold-shock response (cpeE) and enzymes of microaerobic metabolism including those of the phosphotransferase system. Mainly ribosomal, metabolic and pathogenicity-related genes had affected expression in both in vitro-selected biocide mutants and field Salmonella isolates with reduced biocide susceptibility.ConclusionsMultiple pathways can be involved in the adaptation of Salmonella to biocides, mainly related with global stress, or involving metabolic and membrane alterations, and eventually causing “collateral sensitivity” to other antimicrobials. These changes might impact the bacterial-environment interaction, imposing significant bacterial fitness costs which may reduce the chances of fixation and spread of biocide resistant mutants.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2778-z) contains supplementary material, which is available to authorized users.

Review of Antimicrobial Resistance in the Environment and Its Relevance to Environmental Regulators

“…Co-selection is achieved in two ways: (1) co-resistance, whereby selection for one gene fosters the maintenance of another resistance gene, one that does not necessarily offer a selective advantage to the chemical in question (Johnson et al, 2016); and (2) cross-resistance, whereby one resistance gene can offer protection from multiple toxic chemicals (Curiao et al, 2016). Co-resistance is analogous to bringing a toolbox to a worksite; one might only need one or two tools from the toolbox at any one time, but there are many tools ‘fortuitously’ available for use should the need arise.…”

Evolution of Variable Number Tandem Repeats and Its Relationship with Genomic Diversity in Salmonella Typhimurium

“…For instance, STTR5 is located between two domains of YohM, a protein involved in nickel and cobalt resistance (Rodrigue et al, 2005). STTR3 is located between a signal peptide and a polypeptide chain in BigA, a surface-exposed virulence protein (Curiao et al, 2016). The extreme length in STTR5 or STTR3 may affect the stability of YohM and weaken the resistance to nickel and cobalt or reduce the virulence of BigA by interfering with the signal peptide and/or affecting the protein secretion.…”

Effect of Sedimentation and Aeration on Antibiotic Resistance Induction in the Activated Sludge Process

“…The characteristics of wastewater and processes applied in WWTP may select for resistant bacteria and enhance their growth compared to non-resistant strains [10,[12][13][14][15]. We measured viable cell count of the strains before and after induction.…”

“…These characteristics of wastewater and processes applied in WWTP are suspected to help enhance the generation and replication of ARB. In vitro studies showed that detergent, antibiotics, chlorine and biocides may induce antibiotic resistance in bacteria and select for resistant strains [10,[12][13][14][15]. However, whether, how and which processes in WWTP may induce resistance need further investigation.…”