Parallel evolutionary pathways to antibiotic resistance selected by biocide exposure

Objectives Biocides are widely used to prevent infection. We aimed to determine whether exposure of Salmonella to various biocides could act as a driver of antibiotic resistance. Methods Salmonella enterica serovar Typhimurium was exposed to four biocides with differing modes of action. Antibiotic-resistant mutants were selected during exposure to all biocides and characterized phenotypically and genotypically to identify mechanisms of resistance. Results All biocides tested selected MDR mutants with decreased antibiotic susceptibility; these occurred randomly throughout the experiments. Mutations that resulted in de-repression of the multidrug efflux pump AcrAB-TolC were seen in MDR mutants. A novel mutation in rpoA was also selected and contributed to the MDR phenotype. Other mutants were highly resistant to both quinolone antibiotics and the biocide triclosan. Conclusions This study shows that exposure of bacteria to biocides can select for antibiotic-resistant mutants and this is mediated by clinically relevant mechanisms of resistance prevalent in human pathogens.

[1]  A. Litonjua,et al.  Urinary triclosan levels and recent asthma exacerbations. , 2014, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[2]  Dawn Reinhold,et al.  Uptake and accumulation of antimicrobials, triclocarban and triclosan, by food crops in a hydroponic system , 2014, Environmental Science and Pollution Research.

[3]  Jessica M. A. Blair,et al.  RamA, which controls expression of the MDR efflux pump AcrAB-TolC, is regulated by the Lon protease , 2013, The Journal of antimicrobial chemotherapy.

[4]  Xiaoqin Wu,et al.  Comparative uptake and translocation of pharmaceutical and personal care products (PPCPs) by common vegetables. , 2013, Environment international.

[5]  A. Ivens,et al.  Clinically Relevant Mutant DNA Gyrase Alters Supercoiling, Changes the Transcriptome, and Confers Multidrug Resistance , 2013, mBio.

[6]  A. P. Williams,et al.  The role of the natural environment in the emergence of antibiotic resistance in gram-negative bacteria. , 2013, The Lancet. Infectious diseases.

[7]  S. Marathe,et al.  Biocides – resistance, cross-resistance mechanisms and assessment , 2013, Expert opinion on investigational drugs.

[8]  C. Pirard,et al.  Urinary levels of bisphenol A, triclosan and 4-nonylphenol in a general Belgian population. , 2012, Environment international.

[9]  D. Andersson,et al.  Selection of resistance at lethal and non-lethal antibiotic concentrations. , 2012, Current opinion in microbiology.

[10]  F. Tuon,et al.  Risk factors for pan-resistant Pseudomonas aeruginosa bacteremia and the adequacy of antibiotic therapy. , 2012, The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases.

[11]  D. Andersson,et al.  Evolution of antibiotic resistance at non-lethal drug concentrations. , 2012, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[12]  J. Pagés,et al.  Cross-resistance between biocides and antimicrobials: an emerging question. , 2012, Revue scientifique et technique.

[13]  Laura J V Piddock,et al.  The crisis of no new antibiotics--what is the way forward? , 2012, The Lancet. Infectious diseases.

[14]  J. Vila,et al.  The Acinetobacter baumannii Oxymoron: Commensal Hospital Dweller Turned Pan-Drug-Resistant Menace , 2012, Front. Microbio..

[15]  L. Toms,et al.  Triclosan in individual human milk samples from Australia. , 2011, Chemosphere.

[16]  Tim W. Overton,et al.  Exposure of Salmonella enterica Serovar Typhimurium to High Level Biocide Challenge Can Select Multidrug Resistant Mutants in a Single Step , 2011, PloS one.

[17]  A. Boxall,et al.  Impacts of anthropogenic activity on the ecology of class 1 integrons and integron-associated genes in the environment , 2011, The ISME Journal.

[18]  G. Weinstock,et al.  High-throughput whole-genome sequencing to dissect the epidemiology of Acinetobacter baumannii isolates from a hospital outbreak. , 2010, The Journal of hospital infection.

[19]  N. Woodford,et al.  Infections caused by Gram-positive bacteria: a review of the global challenge. , 2009, The Journal of infection.

[20]  D. Hughes,et al.  Interplay in the Selection of Fluoroquinolone Resistance and Bacterial Fitness , 2009, PLoS pathogens.

[21]  I. Paulsen,et al.  RamA Confers Multidrug Resistance in Salmonella enterica via Increased Expression of acrB, Which Is Inhibited by Chlorpromazine , 2008, Antimicrobial Agents and Chemotherapy.

[22]  M. Webber,et al.  Triclosan resistance in Salmonella enterica serovar Typhimurium. , 2008, The Journal of antimicrobial chemotherapy.

[23]  M. Webber,et al.  Proteomic analysis of triclosan resistance in Salmonella enterica serovar Typhimurium. , 2008, The Journal of antimicrobial chemotherapy.

[24]  Mark Webber,et al.  Phenotypic and Proteomic Characterization of Multiply Antibiotic-Resistant Variants of Salmonella enterica Serovar Typhimurium Selected Following Exposure to Disinfectants , 2007, Applied and Environmental Microbiology.

[25]  L. Piddock,et al.  Commonly used farm disinfectants can select for mutant Salmonella enterica serovar Typhimurium with decreased susceptibility to biocides and antibiotics without compromising virulence. , 2007, The Journal of antimicrobial chemotherapy.

[26]  M. Webber,et al.  Prolonged treatment of Salmonella enterica serovar Typhimurium with commercial disinfectants selects for multiple antibiotic resistance, increased efflux and reduced invasiveness. , 2007, The Journal of antimicrobial chemotherapy.

[27]  Michael S McLachlan,et al.  Triclosan in plasma and milk from Swedish nursing mothers and their exposure via personal care products. , 2006, The Science of the total environment.

[28]  K. Mølbak,et al.  Quinolone resistance is associated with increased risk of invasive illness or death during infection with Salmonella serotype Typhimurium. , 2004, The Journal of infectious diseases.

[29]  P. Hawkey.  Mechanisms of quinolone action and microbial response. , 2003, The Journal of antimicrobial chemotherapy.

[30]  J. Andrews,et al.  Determination of minimum inhibitory concentrations. , 2001, The Journal of antimicrobial chemotherapy.

[31]  D. Hooper,et al.  Mechanisms of action of antimicrobials: focus on fluoroquinolones. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[32]  N. Fujita,et al.  Purification and regulatory properties of MarA protein, a transcriptional activator of Escherichia coli multiple antibiotic and superoxide resistance promoters , 1995, Journal of bacteriology.

[33]  S. Nakamura,et al.  Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli , 1990, Antimicrobial Agents and Chemotherapy.

[34]  Welsh,et al.  Bacterial spores and chemical sporicidal agents , 1990, Clinical Microbiology Reviews.

[35]  L. Piddock.  Mechanisms of Fluoroquinolone Resistance: An Update 1994–1998 , 2012, Drugs.

[36]  M. Toleman,et al.  The emergence of pan-resistant Gram-negative pathogens merits a rapid global political response. , 2012, The Journal of antimicrobial chemotherapy.

[37]  H. Imberechts,et al.  The AcrB multidrug transporter plays a major role in high-level fluoroquinolone resistance in Salmonella enterica serovar typhimurium phage type DT204. , 2002, Microbial drug resistance.

[38]  A. Fraise.  Choosing disinfectants. , 1999, The Journal of hospital infection.