A dynamic and complex monochloramine stress response in Escherichia coli revealed by transcriptome analysis Diane Holder a,b,1,2 , David Berry b,c,1 , Dongjuan Dai a,3 , Lutgarde Raskin b , Chuanwu Xi a, * a Department of Environmental Health Sciences, University of Michigan, USA b Department of Civil and Environmental Engineering, University of Michigan, USA c Department of Microbial Ecology, Faculty of Life Sciences, University of Vienna, Austria article info Article history: Received 26 January 2013 Received in revised form 6 May 2013 Accepted 21 May 2013 Available online 31 May 2013 Keywords: Monochloramine Disinfection Microarray Drinking water Biofilm Antibiotic resistance abstract Despite the widespread use of monochloramine in drinking water treatment, there is surprisingly little information about its mode of action. In this study, DNA microarrays were used to investigate the global gene expression of Escherichia coli cells exposed to sub- lethal concentrations of monochloramine, with a focus on temporal dynamics. Genes induced by monochloramine were associated with several stress response functions, including oxidative stress, DNA repair, multidrug efflux, biofilm formation, antibiotic resistance, and cell wall repair. The diversity of functional associations supports a model of monochloramine action involving multiple cellular targets including cell membranes, nucleic acids, and proteins. These data suggest that E. coli responds to monochloramine exposure by activating diverse defense responses rather than a single antioxidant system and the exposure may also induce biofilm formation. The induction of multidrug efflux pumps and specific antibiotic resistance genes further suggests that exposure to mono- chloramine may contribute to reduced susceptibility to some antibiotics. ª 2013 Elsevier Ltd. All rights reserved. 1. Introduction Concerns about the effects of disinfection byproducts, such as trihalomethanes, that result from the use of free chlorine in drinking water treatment have led to increased use of mon- ochloramine as a residual disinfectant in drinking water dis- tribution systems. For example, about 30% of 200 large and medium-sized water treatment systems were using mono- chloramine as a residual disinfectant in 1998 (AWWA, 2000). Currently, this number is expected to be much greater as many utilities have been responding to stricter regulations for disinfection byproducts (Szabo et al., 2008). Monochloramine, like other chlorine-releasing agents, causes oxidative damage to the bacterial cell. While the mode of action of monochloramine has not been elucidated (McDonnell and Russell, 1999), a basic model can be inferred from experi- mental evidence. To assist with this, it is informative to review mechanisms of hypochlorite stress as they have been better * Corresponding author. University of Michigan, School of Public Health, Department of Environmental Health Sciences, 1415 Wash- ington Heights, Ann Arbor, MI, USA. Tel.: þ1 734 615 7594; fax: þ1 734 936 7283. E-mail address: cxi@umich.edu (C. Xi). 1 Contributed equally. 2 Present address: Proficiency and Validation Services Section, USDA-APHIS-FADDL, P.O. Box 848, Greenport, NY 11944-0848, USA. 3 Present address: Biomedical Physical Sciences, 567 Wilson Rd, Rm 6118, East Lansing, MI 48824, USA. Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/watres water research 47 (2013) 4978 e4985 0043-1354/$ e see front matter ª 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.watres.2013.05.041