Increasing Drug Resistance in Vibrio cholerae O1 and non-O1 Strains Isolated from Diarrheal Cases in Japan

Matsushita, Shigeru; Kawamura, Maho; Konishi, Noriko; Kai, Akemi; Katoh, Rei; Ogata, Kazue; Itoh, Tadahiko; Yano, Kazuyoshi; Morita, Koji; Watanabe, Noboru; Kanamori, Masato; Kudoh, Yasuo

doi:10.11150/kansenshogakuzasshi1970.77.195

Cited by 1 publication

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“…As it has very few side effects, cholestyramine is frequently used to treat hypercholesterolemia [43] . Given the increase in numbers of antibiotic-resistant pathogenic bacteria and the emergence of multidrug-resistant strains of vibrios from patients and environmental sources worldwide [44] – [48] , drugs targeted at suppressing bacterial virulence mechanisms instead of killing bacteria or inhibiting their growth (the aims of most conventional antibiotics) constitute an alternative approach to treating infections [49] – [51] . Inactivation of bile acids using sequestrants such as cholestyramine exploits a weakness of T3SS2-positive pathogens and represents a potential novel antivirulence therapy that may attenuate the development of drug-resistant bacteria.…”

Section: Discussionmentioning

confidence: 99%

Bile Acid-Induced Virulence Gene Expression of Vibrio parahaemolyticus Reveals a Novel Therapeutic Potential for Bile Acid Sequestrants

et al. 2010

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Vibrio parahaemolyticus, a bacterial pathogen, causes human gastroenteritis. A type III secretion system (T3SS2) encoded in pathogenicity island (Vp-PAI) is the main contributor to enterotoxicity and expression of Vp-PAI encoded genes is regulated by two transcriptional regulators, VtrA and VtrB. However, a host-derived inducer for the Vp-PAI genes has not been identified. Here, we demonstrate that bile induces production of T3SS2-related proteins under osmotic conditions equivalent to those in the intestinal lumen. We also show that bile induces vtrA-mediated vtrB transcription. Transcriptome analysis of bile-responsive genes revealed that bile strongly induces expression of Vp-PAI genes in a vtrA-dependent manner. The inducing activity of bile was diminished by treatment with bile acid sequestrant cholestyramine. Finally, we demonstrate an in vivo protective effect of cholestyramine on enterotoxicity and show that similar protection is observed in infection with a different type of V. parahaemolyticus or with non-O1/non-O139 V. cholerae strains of vibrios carrying the same kind of T3SS. In summary, these results provide an insight into how bacteria, through the ingenious action of Vp-PAI genes, can take advantage of an otherwise hostile host environment. The results also reveal a new therapeutic potential for widely used bile acid sequestrants in enteric bacterial infections.

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