TY - JOUR
T1 - A next-generation sequencing-based approach to identify genetic determinants of antibiotic resistance in cambodian Helicobacter pylori clinical isolates
AU - Tuan, Vo Phuoc
AU - Narith, Dou
AU - Tshibangu-Kabamba, Evariste
AU - Dung, Ho Dang Quy
AU - Viet, Pham Thanh
AU - Sokomoth, Sin
AU - Binh, Tran Thanh
AU - Sokhem, Sok
AU - Tri, Tran Dinh
AU - Ngov, Seng
AU - Tung, Pham Huu
AU - Thuan, Ngo Phuong Minh
AU - Truc, Tran Cong
AU - Phuc, Bui Hoang
AU - Matsumoto, Takashi
AU - Fauzia, Kartika Afrida
AU - Akada, Junko
AU - Trang, Tran Thi Huyen
AU - Yamaoka, Yoshio
N1 - Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/6
Y1 - 2019/6
N2 - We evaluated the primary resistance of Helicobacter pylori (H. pylori) to routinely used antibiotics in Cambodia, an unexplored topic in the country, and assessed next-generation sequencing’s (NGS) potential to discover genetic resistance determinants. Fifty-five H. pylori strains were successfully cultured and screened for antibiotic susceptibility using agar dilution. Genotypic analysis was performed using NGS data with a CLC genomic workbench. PlasmidSeeker was used to detect plasmids. The correlation between resistant genotypes and phenotypes was evaluated statistically. Resistances to metronidazole (MTZ), levofloxacin (LVX), clarithromycin (CLR), and amoxicillin (AMX) were 96.4%, 67.3%, 25.5%, and 9.1%, respectively. No resistance to tetracycline (TET) was observed. Multi-drug resistance affected 76.4% of strains. No plasmids were found, but genetic determinants of resistance to CLR, LVX, and AMX were 23S rRNA (A2146G and A2147G), GyrA (N87K and D91Y/N/G), and pbp1 (P473L), respectively. No determinants were genetically linked to MTZ or TET resistance. There was high concordance between resistant genotypes and phenotypes for AMX, LVX, and CLR. We observed high antibiotic resistance rates of CLR, MTZ, and LVX, emphasizing the need for periodic evaluation and alternative therapies in Cambodia. NGS showed high capability for detecting genetic resistance determinants and potential for implementation in local treatment policies.
AB - We evaluated the primary resistance of Helicobacter pylori (H. pylori) to routinely used antibiotics in Cambodia, an unexplored topic in the country, and assessed next-generation sequencing’s (NGS) potential to discover genetic resistance determinants. Fifty-five H. pylori strains were successfully cultured and screened for antibiotic susceptibility using agar dilution. Genotypic analysis was performed using NGS data with a CLC genomic workbench. PlasmidSeeker was used to detect plasmids. The correlation between resistant genotypes and phenotypes was evaluated statistically. Resistances to metronidazole (MTZ), levofloxacin (LVX), clarithromycin (CLR), and amoxicillin (AMX) were 96.4%, 67.3%, 25.5%, and 9.1%, respectively. No resistance to tetracycline (TET) was observed. Multi-drug resistance affected 76.4% of strains. No plasmids were found, but genetic determinants of resistance to CLR, LVX, and AMX were 23S rRNA (A2146G and A2147G), GyrA (N87K and D91Y/N/G), and pbp1 (P473L), respectively. No determinants were genetically linked to MTZ or TET resistance. There was high concordance between resistant genotypes and phenotypes for AMX, LVX, and CLR. We observed high antibiotic resistance rates of CLR, MTZ, and LVX, emphasizing the need for periodic evaluation and alternative therapies in Cambodia. NGS showed high capability for detecting genetic resistance determinants and potential for implementation in local treatment policies.
KW - Antibiotic resistance
KW - Genetic determinants
KW - Helicobacter pylori
KW - Mutation
KW - Next-generation sequencing
KW - Whole genome sequence
UR - http://www.scopus.com/inward/record.url?scp=85071462754&partnerID=8YFLogxK
U2 - 10.3390/jcm8060858
DO - 10.3390/jcm8060858
M3 - Article
AN - SCOPUS:85071462754
SN - 2077-0383
VL - 8
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 6
M1 - 858
ER -