Original Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Feb 28, 2009; 15(8): 919-926
Published online Feb 28, 2009. doi: 10.3748/wjg.15.919
Aspirin increases susceptibility of Helicobacter pylori to metronidazole by augmenting endocellular concentrations of antimicrobials
Xiao-Ping Zhang, Wei-Hong Wang, Yu Tian, Wen Gao, Jiang Li
Xiao-Ping Zhang, Wei-Hong Wang, Yu Tian, Wen Gao, Jiang Li, Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China
Author contributions: Zhang XP performed most parts of the experiment and wrote the manuscript; Wang WH designed the study and wrote the manuscript; Tian Y, Gao W, Li J offered the technical assistance.
Correspondence to: Wei-Hong Wang, Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China. wangweihong@medmail.com.cn
Telephone: +86-10-66551122
Fax: +86-10-66518105
Received: October 10, 2008
Revised: January 17, 2009
Accepted: January 24, 2009
Published online: February 28, 2009

AIM: To investigate the mechanisms of aspirin increasing the susceptibility of Helicobacter pylori (H pylori) to metronidazole.

METHODS: H pylori reference strain 26 695 and two metronidazole-resistant isolates of H pylori were included in this study. Strains were incubated in Brucella broth with or without aspirin (1 mmol/L). The rdxA gene of H pylori was amplified by PCR and sequenced. The permeability of H pylori to antimicrobials was determined by analyzing the endocellular radioactivity of the cells after incubated with [7-3H]-tetracycline. The outer membrane proteins (OMPs) of H pylori 26 695 were depurated and analyzed by SDS-PAGE. The expression of 5 porins (hopA, hopB, hopC, hopD and hopE) and the putative RND efflux system (hefABC) of H pylori were analyzed using real-time quantitative PCR.

RESULTS: The mutations in rdxA gene did not change in metronidazole resistant isolates treated with aspirin. The radioactivity of H pylori increased when treated with aspirin, indicating that aspirin improved the permeability of the outer membrane of H pylori. However, the expression of two OMP bands between 55 kDa and 72 kDa altered in the presence of aspirin. The expression of the mRNA of hopA, hopB, hopC, hopD, hopE and hefA, hefB, hefC of H pylori did not change when treated with aspirin.

CONCLUSION: Although aspirin increases the susceptibility of H pylori to metronidazole, it has no effect on the mutations of rdxA gene of H pylori. Aspirin increases endocellular concentrations of antimicrobials probably by altering the OMP expression.

Keywords: Helicobacter pylori, Aspirin, Metronidazole, Resistance, Minimum inhibitory concentrations