Letters To The Editor
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2017; 23(33): 6194-6196
Published online Sep 7, 2017. doi: 10.3748/wjg.v23.i33.6194
Comment on “Effect of biofilm formation by clinical isolates of Helicobacter pylori on the efflux-mediated resistance to commonly used antibiotics”
Evangelos I Kazakos, Nick Dorrell, Stergios A Polyzos, Georgia Deretzi, Jannis Kountouras
Evangelos I Kazakos, Stergios A Polyzos, Jannis Kountouras, Department of Medicine, the Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, 54642 Thessaloniki, Greece
Nick Dorrell, Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
Georgia Deretzi, Department of Neurology, Multiple Sclerosis Unit, Papageorgiou General Hospital, 54629 Thessaloniki, Greece
Author contributions: Kazakos EI, Polyzos SA, Deretzi G and Kountouras J wrote the letter; Dorrell N and Kountouras J revised the manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Evangelos I Kazakos, MD, PhD, MSc, DTM&H, Department of Medicine, the Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece, Biopathology Labs SA, 50132 Kozani, Greece. ekazakos@gmail.com
Telephone: +30-246-1026775 Fax: +30-246-1026475
Received: May 1, 2017
Peer-review started: May 3, 2017
First decision: June 5, 2017
Revised: June 27, 2017
Accepted: July 22, 2017
Article in press: July 24, 2017
Published online: September 7, 2017
Abstract

Attaran et al[1] have recently shown that decreased susceptibility of established Helicobacter pylori (H. pylori) biofilms to specific antibiotics, was associated with the overtly enhanced transcription of two efflux pump genes, hp1165 and hefA, involved in specific resistance to tetracycline and multiple antibiotics, respectively. Apart from antibiotic exposure, secretion of multiple antimicrobial peptides, such as human β-defensins (hβDs), by the gastric epithelium upon Hp challenge, may act as early triggering events that positively impact biofilm formation and thus, antibiotic resistance. In this regard, we undertook genomic transcriptional studies using Hp 26695 strain following exposure to sublethal, similar to those present in the gastric niche, concentrations of hβDs in an attempt to provide preliminary data regarding possible mechanisms of immune evasion and selective sensitivity of Hp. Our preliminary results indicate that hβD exposure ignites a rapid response that is largely due to the activation of several, possibly interconnected transcriptional regulatory networks – origons - that ultimately coordinate cellular processes needed to maintain homeostasis and successful adaptation of the bacterium in the gastric environment. In addition, we have shown that both antibiotic and hβD resistance are mediated by dedicated periplasmic transporters, including the aforementioned efflux pump genes hp1165 and hefA, involved in active export of antibiotics from the cell membrane and/or, as recently suggested, substrate sensing and signalling. Furthermore, it appears that sublethal doses of hβDs may enhance biofilm formation by the sustained expression of, mainly, quorum sensing-related genes. In conclusion, we provide additional data regarding the role of specific innate immune molecules in antibiotic cross-resistance mechanisms that may deepen our understanding in the context of the development of novel eradication regimens.

Keywords: Helicobacter pylori, Human β-defensins, Biofilm, Antimicrobial resistance

Core tip: In the course of Helicobacter pylori infection, epithelium-derived human β-defensins may act as early triggering signals that induce biofilm formation and enhanced expression of antibiotic resistance genes, regardless of prior antibiotic exposure.