AUTHOR=Zhong Yuanzun , Tang Liyao , Deng Qiuhua , Jing Li , Zhang Jiao , Zhang Yao , Yu Feng , Ou Yijun , Guo Shaoju , Huang Bin , Cao Hongying , Huang Ping , Xu Yifei 

TITLE=Unraveling the Novel Effect of Patchouli Alcohol Against the Antibiotic Resistance of Helicobacter pylori

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.674560

DOI=10.3389/fmicb.2021.674560

ISSN=1664-302X

ABSTRACT=<p>The long-term colonization of <italic>Helicobacter pylori</italic> can cause various gastrointestinal diseases, and its high genetic variability is prone to antibiotic resistance and leads to failure of clinical treatment. Intracellular survival also contributes to the drug tolerance of <italic>H. pylori</italic>. Patchouli alcohol (PA) shows a highly efficient activity against <italic>H. pylori in vitro</italic> and <italic>in vivo</italic>. And this study aims to explore whether PA can reduce the resistance of <italic>H. pylori</italic> and determine the underlying mechanism. Checkerboard and time–kill bactericidal curve assay reveal that the combination of PA and clarithromycin (CLR) promoted the inhibition and bactericidal effect against <italic>H. pylori</italic>. Stimulation of CLR leads to the internalization of <italic>H. pylori</italic>, but PA can effectively inhibit the invasion induced by CLR. Compared with antibiotics, PA remarkably eradicated the intracellular <italic>H. pylori</italic>, and this intracellular sterilized ability was further improved in combination with antibiotics (CLR and metronidazole). The expression of <italic>H. pylori</italic> efflux pump genes (<italic>hp0605</italic>, <italic>hp1327</italic>, and <italic>hp1489</italic>) was dose-dependently downregulated by PA. Digital droplet PCR indicated that the <italic>H. pylori</italic> mutant of A2143G can be inhibited by PA. Cellular uptake and transport assays showed that PA is rapidly absorbed, which promotes its activity against intracellular bacteria. Therefore, PA can act synergistically with CLR as a candidate treatment against drug-resistant <italic>H. pylori</italic>.</p>