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

Keerthi S. Guruge, Noriko Yamanaka, Miyuki Sonobe, Wataru Fujizono, Miyako Yoshioka, Masato Akiba, Takehisa Yamamoto, Derrick I. Joshua, Keshava Balakrishna, Nobuyoshi Yamashita, Kurunthachalam Kannan, Toshiyuki Tsutsui

Research output: Contribution to journalArticle

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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 factormediated 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 premonsoon 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.

Original languageEnglish
Article numbere0138391
JournalPLoS One
Volume10
Issue number9
DOIs
Publication statusPublished - 18-09-2015

Fingerprint

Waste Water
Gene expression
Escherichia coli
hepatocytes
wastewater
Rats
Hepatocytes
Sewage treatment plants
Wastewater
Sewage
Transcription Factors
sewage treatment
transcription factors
anti-infective agents
Gene Expression
gene expression
Genes
rats
cytochrome P-450
Cytochrome P-450 Enzyme System

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Guruge, Keerthi S. ; Yamanaka, Noriko ; Sonobe, Miyuki ; Fujizono, Wataru ; Yoshioka, Miyako ; Akiba, Masato ; Yamamoto, Takehisa ; Joshua, Derrick I. ; Balakrishna, Keshava ; Yamashita, Nobuyoshi ; Kannan, Kurunthachalam ; Tsutsui, Toshiyuki. / 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. In: PLoS One. 2015 ; Vol. 10, No. 9.
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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. / Guruge, Keerthi S.; Yamanaka, Noriko; Sonobe, Miyuki; Fujizono, Wataru; Yoshioka, Miyako; Akiba, Masato; Yamamoto, Takehisa; Joshua, Derrick I.; Balakrishna, Keshava; Yamashita, Nobuyoshi; Kannan, Kurunthachalam; Tsutsui, Toshiyuki.

In: PLoS One, Vol. 10, No. 9, e0138391, 18.09.2015.

Research output: Contribution to journalArticle

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T1 - 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

AU - Guruge, Keerthi S.

AU - Yamanaka, Noriko

AU - Sonobe, Miyuki

AU - Fujizono, Wataru

AU - Yoshioka, Miyako

AU - Akiba, Masato

AU - Yamamoto, Takehisa

AU - Joshua, Derrick I.

AU - Balakrishna, Keshava

AU - Yamashita, Nobuyoshi

AU - Kannan, Kurunthachalam

AU - Tsutsui, Toshiyuki

PY - 2015/9/18

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