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Antimicrobial Agents and Chemotherapy, April 2005, p. 1477-1482, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1477-1482.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Helicobacter pylori TolC Efflux Pump Confers Resistance to Metronidazole

Karin van Amsterdam,1 Aldert Bart,1 and Arie van der Ende1*

Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands1

Received 3 September 2004/ Returned for modification 23 October 2004/ Accepted 6 December 2004

In Helicobacter pylori, the contribution of efflux proteins to antibiotic resistance is not well established. As translocases that act in parallel may have overlapping substrate specificities, the loss of function of one such translocase may be compensated for by that of another translocase with no effect on susceptibilities to antibiotics. The genome of H. pylori 26695 was assessed for the presence of putative translocases and outer membrane efflux or TolC-like proteins which could interact to form efflux systems involved in drug resistance. Twenty-seven translocases were identified, of which HP1184 was the sole representative of the multidrug and toxic compound extrusion family of translocases and which could thus have a unique substrate specificity. In addition, four TolC-like proteins (HP0605, HP0971, HP1327, and HP1489) were identified. Thus, it is feasible that inactivation of a TolC-like protein would affect the functions of multiple translocases. We aimed to determine whether efflux systems contribute to antimicrobial susceptibility by evaluation of the susceptibility profiles of an HP1184-knockout mutant, four mutants in which one of the four TolC homologs was inactivated, as well as a mutant in which both HP0605 and HP0971 were inactivated. The HP1184- and HP1489-knockout mutants both showed increased susceptibilities to ethidium bromide, while the HP0605-knockout mutant exhibited increased susceptibilities to novobiocin and sodium deoxycholate. The HP0605 and HP0971 double-knockout mutant was also more susceptible to metronidazole, in addition to being susceptible to novobiocin and sodium deoxycholate. Thus, active efflux is an eminent means of resistance to antimicrobials in H. pylori and resembles the situation in other bacteria.

* Corresponding author. Mailing address: Academic Medical Center, Department of Medical Microbiology, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. Phone: 31-20-5664862. Fax: 31-20-6979271. E-mail: a.vanderende{at}amc.uva.nl.

Antimicrobial Agents and Chemotherapy, April 2005, p. 1477-1482, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1477-1482.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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