Global Antimicrobial Resistance Gene Study of <i>Helicobacter pylori</i>: Comparison of Detection Tools, ARG and Efflux Pump Gene Analysis, Worldwide Epidemiological Distribution, and Information Related to the Antimicrobial-Resistant Phenotype
Ricky Indra Alfaray,
Batsaikhan Saruuljavkhlan,
Kartika Afrida Fauzia,
Roberto C. Torres,
Kaisa Thorell,
Selva Rosyta Dewi,
Kirill A. Kryukov,
Takashi Matsumoto,
Junko Akada,
Ratha-korn Vilaichone,
Muhammad Miftahussurur,
Yoshio Yamaoka
Affiliations
Ricky Indra Alfaray
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Oita 879-5593, Japan
Batsaikhan Saruuljavkhlan
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Oita 879-5593, Japan
Kartika Afrida Fauzia
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Oita 879-5593, Japan
Roberto C. Torres
The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China
Kaisa Thorell
Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, 405 30 Gothenburg, Sweden
Selva Rosyta Dewi
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Oita 879-5593, Japan
Kirill A. Kryukov
Biological Networks Laboratory, Department of Informatics, National Institute of Genetics, Shizuoka 411-8540, Japan
Takashi Matsumoto
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Oita 879-5593, Japan
Junko Akada
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Oita 879-5593, Japan
Ratha-korn Vilaichone
Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Thammasat University Hospital, Khlong Nueng 12120, Pathumthani, Thailand
Muhammad Miftahussurur
<i>Helicobacter pylori</i> and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60286, Indonesia
Yoshio Yamaoka
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Oita 879-5593, Japan
We conducted a global-scale study to identify H. pylori antimicrobial-resistant genes (ARG), address their global distribution, and understand their effect on the antimicrobial resistance (AMR) phenotypes of the clinical isolates. We identified ARG using several well-known tools against extensive bacterial ARG databases, then analyzed their correlation with clinical antibiogram data from dozens of patients across countries. This revealed that combining multiple tools and databases, followed by manual selection of ARG from the annotation results, produces more conclusive results than using a single tool or database alone. After curation, the results showed that H. pylori has 42 ARG against 11 different antibiotic classes (16 genes related to single antibiotic class resistance and 26 genes related to multidrug resistance). Further analysis revealed that H. pylori naturally harbors ARG in the core genome, called the ‘Set of ARG commonly found in the Core Genome of H. pylori (ARG-CORE)’, while ARG-ACC—the ARG in the accessory genome—are exclusive to particular strains. In addition, we detected 29 genes of potential efflux pump-related AMR that were mostly categorized as ARG-CORE. The ARG distribution appears to be almost similar either by geographical or H. pylori populations perspective; however, some ARG had a unique distribution since they tend to be found only in a particular region or population. Finally, we demonstrated that the presence of ARG may not directly correlate with the sensitive/resistance phenotype of clinical patient isolates but may influence the minimum inhibitory concentration phenotype.
