title: Source-Related Effects of Wastewater on Transcription Factor (AhR, CAR and PXR)-Mediated Induction of Gene Expression in Cultured Rat Hepatocytes and Their Association with the Prevalence of Antimicrobial-Resistant Escherichia coli.
abstract: Extracts of wastewater collected from 4 sewage treatment plants (STPs) receiving effluents from different sources in South India were investigated for their levels of transcription factor-mediated gene induction in primary cultured rat hepatocytes. In addition, the relation between gene induction levels and the prevalence of antimicrobial-resistant Escherichia coli (E. coli) in wastewater was examined. STP-3, which treats only hospital wastewater, exhibited significantly greater induction potency of all 6 drug metabolizing cytochrome P450 (CYP) genes examined, CYP1A1, 1A2, 1B1, 2B15, 3A1, and 3A2, whereas the wastewater at STP-1, which exclusively receives domestic sewage, showed significantly diminished levels of induction of 3 CYP genes when compared to the levels of CYP induction at STP-2, which receives mixed wastewater. Samples collected during the monsoon season showed a significantly altered gene induction capacity compared to that of samples from the pre-monsoon period. The data suggest that the toxicity of wastewater in STPs was not significantly diminished during the treatment process. The chemical-gene interaction data predicted that a vast number of chemicals present in the wastewater would stimulate the genes studied in the rat hepatocytes. The multivariable logistic regression analysis demonstrated that the prevalence of isolates resistant to cefotaxime, imipenem and streptomycin was significantly correlated with the levels of induction of at least three CYP-isozymes in STP wastewater. In addition, the resistance of isolates in treatment plants was not altered by the treatment steps, whereas the sampling season did have an impact on the resistance to specific antimicrobials. The identification of receptor-mediated gene regulation capacities offers important data not limited to the (synergistic) physiological role of chemicals in biological systems but may provide new insight into the link between the effects of known/unknown drugs and prevalence of antimicrobial-resistant bacteria in wastewater.
authors.affiliation: Pathology and Pathophysiology Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Keerthi S
authors.initials: KS
authors.lastname: Guruge
authors.affiliation: Pathology and Pathophysiology Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamanaka
authors.affiliation: Pathology and Pathophysiology Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan; Central Livestock Hygiene Service Center, Wakakusu, Saga, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Sonobe
authors.affiliation: Pathology and Pathophysiology Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan; Central Livestock Hygiene Service Center, Jonan, Minami-Ku, Kumamoto, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Fujizono
authors.affiliation: Pathology and Pathophysiology Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Yoshioka
authors.affiliation: Bacterial and Parasitic Disease Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Akiba
authors.affiliation: Viral Diseases and Epidemiology Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Takehisa
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Civil Engineering, Manipal Institute of Technology, Manipal University, Manipal, Karnataka, India.
authors.forename: Derrick I
authors.initials: DI
authors.lastname: Joshua
authors.affiliation: Department of Civil Engineering, Manipal Institute of Technology, Manipal University, Manipal, Karnataka, India.
authors.forename: Keshava
authors.initials: K
authors.lastname: Balakrishna
authors.affiliation: National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Yamashita
authors.affiliation: Wadsworth Center, New York State Department of Health and Department of Environmental Health Sciences, State University of New York at Albany, Albany, New York, United States of America.
authors.forename: Kurunthachalam
authors.initials: K
authors.lastname: Kannan
authors.affiliation: Viral Diseases and Epidemiology Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tsutsui
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics / Q000302:isolation & purification*; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism*; D007194:India; D051381:Rats; D012722:Sewage / Q000382:microbiology; D062065:Wastewater / Q000382:microbiology*
chemical_list: D003577:Cytochrome P-450 Enzyme System; D012722:Sewage; D062065:Wastewater