Three RND efflux systems had been identified in H pylori, namely hefABC, hefDEF, and hefGHI, each of which consisted of a translocase, an accessory protein. But the contribution of efflux proteins to antibiotic resistance is not well established. 27 putative translocases also had been identified in the H pylori 26695 genome, but only four putative H pylori OEPs or TolC homologs were identified. While they could not quantitate the operons expression levels of the efflux systems in multidrug resistance strains of H pylori.
A research article to be published on September 7, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Prof. Zheng from Zhengzhou University used fluorescence real-time quantitative PCR to study the levels of mRNA expression of hefA in MDR strains and its parent strains. To futher evaluate the contribution of hefA in multidrug resistance of H pylori, the article also constructed an H pylori mutant strain (△H. pylori LZ1026), and detected the susceptibility to 10 antimicrobials of the △H pylori LZ1026 with a more sensitive method of twofold agar dilution tests.
Six multidrug-resistant strains (including 5 clinical isolates and H pylori NCTC11637) were selected, and their MICs showed a significant (≥ 4-fold) increase than their parent strains. The expression levels of hefA gene in the MDR strains were significantly higher compared with their parent strains (P = 0.033). An H pylori LZ1026 mutant was successfully constructed and the △H pylori LZ1026 was more susceptible to four of the 10 antibiotics. All 20 strains displayed transcripts for hefA that confirmed the in vitro expression of these genes.
The results revealed that the relative expression of hefA in the induced multidrug resistant strains were higher than those in their wild susceptible isolates. It has shown that similar to other gram-negative organisms, the H pylori hefA mutant displayed increased susceptibilities to antibiotics. It confirmed that high expression of the hefA plays an important role in multidrug-resistance of H pylori. H pylori contains an active multidrug efflux mechanism and therefore compound efflux needs to be taken into account when determining resistance mechanisms in this organism.
Reference: Liu ZQ, Zheng PY, Yang PC. Efflux pump gene hefA of Helicobacter pylori plays an important role in multidrug resistance.World J Gastroenterol 2008; 14(33): 5217-5222
Correspondence to: Dr. Peng-Yuan Zheng, Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, 2 Jingba Road, Zhengzhou 450014, Henan Province, China. email@example.com
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.