Helicobacter pylori Biofilm Confers Antibiotic Tolerance in Part via A Protein-Dependent Mechanism

Abstract

<i>Helicobacter pylori</i>, a WHO class I carcinogen, is one of the most successful human pathogens colonizing the stomach of over 4.4 billion of the world's population. Antibiotic therapy represents the best solution but poor response rates have hampered the elimination of <i>H. pylori</i>. A growing body of evidence suggests that <i>H. pylori</i> forms biofilms, but the role of this growth mode in infection remains elusive. Here, we demonstrate that <i>H. pylori</i> cells within a biofilm are tolerant to multiple antibiotics in a manner that depends partially on extracellular proteins. Biofilm-forming cells were tolerant to multiple antibiotics that target distinct pathways, including amoxicillin, clarithromycin, and tetracycline. Furthermore, this tolerance was significantly dampened following proteinase K treatment. These data suggest that <i>H. pylori</i> adapts its phenotype during biofilm growth resulting in decreased antibiotic susceptibility but this tolerance can be partially ameliorated by extracellular protease treatment.