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Selection of target mutation in rat gastrointestinal tract E. coli by minute dosage of enrofloxacin.

ABSTRACT: It has been suggested that bacterial resistance is selected within a mutation selection window of antibiotics. More recent studies showed that even extremely low concentration of antibiotic could select resistant bacteria in vitro. Yet little is known about the exact antibiotic concentration range that can effectively select for resistant organisms in animal gastrointestinal (GI) tract. In this study, the effect of different dosages of enrofloxacin on resistance and mutation development in rat GI tract E. coli was investigated by determining the number of resistant E. coli recoverable from rat fecal samples. Our data showed that high dose antibiotic treatment could effectively eliminate E. coli with single gyrA mutation in the early course of treatment, yet the eradication effects diminished upon prolonged treatment. Therapeutic and sub-therapeutic dose (1/10 and 1/100 of therapeutic doses) of enrofloxacin could effectively select for mutation in GI tract E. coli at the later course of enrofloxacin treatment and during the cessation periods. Surprisingly, very low dose of enrofloxacin (1/1000 therapeutic dose) could also select for mutation in GI tract E. coli at the later course of enrofloxacin treatment, only with slightly lower efficiency. No enrofloxacin-resistant E. coli could be selected at all test levels of enrofloxacin during long term treatment and the strength of antibiotic treatment does not alter the overall level of E. coli in rat GI tract. This study demonstrated that long term antibiotic treatment seems to be the major trigger for the development of target mutations in GI tract E. coli, which provided insight into the rational use of antibiotics in animal husbandry.

SUBMITTER: Lin D

PROVIDER: S-EPMC4154546 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Selection of target mutation in rat gastrointestinal tract E. coli by minute dosage of enrofloxacin.

Lin Dachuan D Chen Kaichao K Li Ruichao R Liu Lizhang L Guo Jiubiao J Yao Wen W Chen Sheng S

Frontiers in microbiology 20140904

It has been suggested that bacterial resistance is selected within a mutation selection window of antibiotics. More recent studies showed that even extremely low concentration of antibiotic could select resistant bacteria in vitro. Yet little is known about the exact antibiotic concentration range that can effectively select for resistant organisms in animal gastrointestinal (GI) tract. In this study, the effect of different dosages of enrofloxacin on resistance and mutation development in rat G ...[more]

PMID: 25237308

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Project description:Background: The molecular basis of segment specific epithelial functions of the stomach and bowel has not been established. Regionally unique molecular properties of epithelial cells can be identified using cell-specific gene expression in each epithelial region by comparative mRNA analysis. Aim: To describe segment-specific epithelial mRNA content by comparative mRNA analysis of purified epithelial cell suspensions of stomach, small and large bowel. Results: 12% of all annotated genes show segment specific enrichment. The gastric (>3000 genes) and ileal (519 genes) mucosa show the most diverse expression profile. (a) Stomach: The gastric mucosa expresses the machinery for acid secretion, digestive enzyme release, and hormone release by gastric enteroendocrine cells. Associated with acid secretion is a specific set of K+, Cl-, and bicarbonate channels. Novel is a pathway for glucose and fatty acid sensing, iodine and glutamate uptake, and taurine synthesis. Specific sets of transcription factors control epithelial (Barx1, Runx) and enteroendocrine (FoxA2/N4) cell differentiation. (b) Small Bowel: This epithelium expresses genes coding for a unique fructose/glucose uptake and utilization mechanism. Enteroendocrine signalling to the gastric function is present. The upper portion expresses genes for iron uptake, bicarbonate secretion, and detoxification of food contents. Epithelial differentiation is transcriptionally controlled by Meis2/Pdx1 and Onecut 2. Expression of digestive enzymes, lipid/bile acid uptake and utilization increases distally. The ileal epithelium is also involved in innate and acquired immune defence, regulation of motility, and electrolyte and water re-absorption. Transcriptional regulation of enterocyte and goblet cell differentiation is mainly controlled by increasing expression of Cdx1 and 2. (c) Colon: This epithelium is mainly involved in Ca++-, K+, and water re-absorption, fatty acid uptake and sensing, and innate and acquired immune defence. Epithelial differentiation is controlled by Hox transcription factors in addition to Cdx1/2. Conclusion: This regional survey of gene expression by the GI tract epithelium reveals unique epithelial properties, raising several important questions as to the role of the proteins encoded in gut physiology.

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Dataset Information

Selection of target mutation in rat gastrointestinal tract E. coli by minute dosage of enrofloxacin.

Publications

Selection of target mutation in rat gastrointestinal tract E. coli by minute dosage of enrofloxacin.

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