| Title: |
Genomic determinants of antibiotic resistance for Helicobacter pylori treatment: a retrospective phenotypic and genotypic observational study |
| Authors: |
Martínez-Martínez, Francisco José; Chiner-Oms, Álvaro; Furió, Victoria; HpGP Research Network; Yamaoka, Yoshio; Dekker, John P; Mégraud, Francis; Bénéjat, Lucie; Ducournau, Astrid; Giese, Alban; Jehanne, Quentin; Jauvain, Marine; Camargo, M Constanza; Comas, Iñaki; Lehours, Philippe; Varon, Christine; Romero-Gallo, Judith; Krishna, Uma; Peek, Richard M; Piazuelo, M Blanca; Wilson, Keith T; Loh, John T; Cover, Timothy L; Vale, Filipa F; Raaf, Naïma; Aftab, Hafeza; Akada, Junko; Matsumoto, Takashi; Haesebrouck, Freddy; Bartelli, Thais F; Nunes, Diana Noronha; Pelosof, Adriane; Sztokfisz, Claudia Zitron; Dias-Neto, Emmanuel; Assumpção, Paulo Pimentel; Karagyozov, Petko; Tishkov, Ivan; Goodman, Karen J; Geary, Janis; Cromarty, Taylor J; Price, Nancy L; Quilty, Douglas; Corvalan, Alejandro H; Gonzalez, Robinson; Riquelme, Arnoldo; García-Cancino, Apolinaria; Parra-Sepúlveda, Cristian; Castillo, Francisco; Bravo, Maria Mercedes; Pazos, Alvaro; Bravo, Luis E; Fox, James G; Ramírez-Mayorga, Vanessa; Molina-Castro, Silvia; Durán-Bermúdez, Sundry; Campos-Núñez, Christian; Chaves-Cervantes, Manuel; Tshibangu-Kabamba, Evariste; Tumba, Ghislain Disashi; Tshimpi-Wola, Antoine; de Jesus Ngoma-Kisoko, Patrick; Tshibangu, Fabien Mbaya; Mukanya, Alain Cimuanga; Nkomba, Tressy Kalenga; Cruz, Modesto; Abreu, José Jiménez; Secka, Ousman; Link, Alexander; Malfertheiner, Peter; Adinortey, Michael Buenor; Bockarie, Ansumana Sandy; Adinortey, Cynthia Ayefoumi; Ofori, Eric Gyamerah; Sgouras, Dionyssios N; Martinez-Gonzalez, Beatriz; Michopoulos, Spyridon; Georgopoulos, Sotirios; Hernandez, Elisa; Dominguez, Ricardo L; Morgan, Douglas R; Harðardóttir, Hjördís; Gunnarsdóttir, Anna Ingibjörg; Guðjónsson, Hallgrímur; Jónasson, Jón Gunnlaugur; Björnsson, Einar S; Ballal, Mamatha; Shetty, Vignesh; Miftahussurur, Muhammad; Sugihartono, Titong; Alfaray, Ricky Indra; Waskito, Langgeng Agung; Fauzia, Kartika Afrida; Syam, Ari Fahrial; Maulahela, Hasan; Malekzadeh, Reza; Peretz, Avi; Azrad, Maya; On, Avi; De Re, Valli; Zanussi, Stefania; Cannizzaro, Renato; Canzonieri, Vincenzo; Shimura, Takaya; Tokunaga, Kengo; Osaki, Takako; Kamiya, Shigeru; Jadallah, Khaled; Matalka, Ismail; Igissin, Nurbek Sagynbekuly; Moldobaeva, Mariia Satarovna; Rakhat, Attokurova; Choi, Il Ju; Kim, Jae Gyu; Kim, Nayoung; Leja, Mārcis; Vangravs, Reinis; Šķenders, Ģirts; Rūdule, Aiga; Kikuste, Ilze; Vanags, Aigars; Rudzīte, Dace; Kupcinskas, Juozas; Kiudeliene, Edita; Kiudelis, Vytautas; Gedgaudas, Rolandas; Jonaitis, Paulius; Kiudelis, Gediminas; Jonaitis, Laimas; Skieceviciene, Jurgita; Vadivelu, Jamuna; Loke, Mun Fai; Vellasamy, Kumutha Malar; Herrera-Goepfert, Roberto; Alonso-Larraga, Juan Octavio; Yee, Than Than; Htet, Kyaw; Matsuhisa, Takeshi; Shrestha, Pradeep Krishna; Ansari, Shamshul; Abiodun, Olumide; Jemilohun, Christopher; Akande, Kolawole Oluseyi; Olu-Abiodun, Oluwatosin; Magaji, Francis Ajang; Omotoso, Ayodele; Okonkwo, Uchenna; Osuagwu, Chukwuemeka Chukwunwendu; Owoseni, Opeyemi O; Castaneda, Carlos; Castillo, Miluska; Velapatino, Billie; Gilman, Robert H; Krzyżek, Paweł; Gościniak, Grażyna; Pawełka, Dorota; Korona-Glowniak, Izabela; Cichoz-Lach, Halina; Oleastro, Mónica; Figueiredo, Ceu; Machado, Jose C; Ferreira, Rui M; Bordin, Dmitry S; Livzan, Maria A; Tsukanov, Vladislav V; Tan, Patrick; Yeoh, Khay Guan; Zhu, Feng; Ally, Reid; Haas, Rainer; Fischer, Wolfgang; Montes, Milagrosa; Fernández-Reyes, María; Tamayo, Esther; Lizasoain, Jacobo; Bujanda, Luis; Lario, Sergio; Ramírez-Lázaro, María José; Calvet, Xavier; Brunet-Mas, Eduard; Domper-Arnal, María José; García-Mateo, Sandra; Abad-Baroja, Daniel; Delgado-Guillena, Pedro; Moreira, Leticia; Botargues, Josep; Pérez-Martínez, Isabel; Barreiro-Alonso, Eva; Flores, Virginia; Gisbert, Javier P; Muro, Edurne Amorena; Linares, Pedro; Alcoba, Laura; Martin, Vicente; Engstrand, Lars; Enroth, Helena; Keller, Peter M; Wagner, Karoline; Pohl, Daniel; Lee, Yi-Chia; Liou, Jyh-Ming; Wu, Ming-Shiang; Kocazeybek, Bekir; Sarıbas, Suat; Tasçı, İhsan; Demiryas, Süleyman; Kepil, Nuray; Quiel, Luis; Villagra, Miguel; Norton, Morgan; Johnson, Deborah; Huang, Robert J; Hwang, Joo Ha; Szymczak, Wendy; Jacobs, William R; In, Haejin; Bollag, Roni; Lopez, Aileen; Kruse, Edward J; White, Joseph; Lane, Charlotte; Gao, Yang; Gold, Benjamin D; Cruz-Correa, Marcia; González-Pons, María; Rodriguez, Luz M; Tuan, Vo Phuoc; Quy Dung, Ho Dang; Binh, Tran Thanh; Huyen Trang, Tran Thi; Van Khien, Vu; Katsura, Yukako; Gonzalez-Hormazabal, Patricio; Tarazona-Santos, Eduardo; Zamudio, Roxana; Mariño-Ramírez, Leonardo; Backert, Steffen; Naumann, Michael; Smet, Annemieke; Berg, Douglas E; Yahara, Koji; Blaser, Martin J; Vincze, Tamas; Morgan, Richard D; Roberts, Richard J; Torres, Javier; Torres, Roberto C; Noureen, Mehwish; Cherry, Joshua L; Osada, Naoki; Fukuyo, Masaki; Arita, Masanori; Sandoval-Motta, Santiago; Agostini, Rajiv Boscolo; Ghirotto, Silvia; Muñoz-Ramírez, Zilia Y; Falush, Daniel; Thorell, Kaisa; Uchiyama, Ikuo; Kobayashi, Ichizo; Wang, Difei; Hicks, Belynda; Yeager, Meredith; Hutchinson, Amy; Teshome, Kedest; Jones, Kristie; Luo, Wen; Goldstein, Alisa M; Hu, Nan; Taylor, Philip R; Song, Minkyo; Yu, Kai; Zhu, Bin; Abnet, Christian C; Rabkin, Charles S |
| Contributors: |
Martínez-Martínez, Francisco José; Chiner-Oms, Álvaro; Furió, Victoria; Hpgp Research, Network; Yamaoka, Yoshio; Dekker, John P; Mégraud, Franci; Bénéjat, Lucie; Ducournau, Astrid; Giese, Alban; Jehanne, Quentin; Jauvain, Marine; Camargo, M Constanza; Comas, Iñaki; Lehours, Philippe; Varon, Christine; Romero-Gallo, Judith; Krishna, Uma; Peek, Richard M; Piazuelo, M Blanca; Wilson, Keith T; Loh, John T; Cover, Timothy L; Vale, Filipa F; Raaf, Naïma; Aftab, Hafeza; Akada, Junko; Matsumoto, Takashi; Haesebrouck, Freddy; Bartelli, Thais F; Nunes, Diana Noronha; Pelosof, Adriane; Sztokfisz, Claudia Zitron; Dias-Neto, Emmanuel; Assumpção, Paulo Pimentel; Karagyozov, Petko; Tishkov, Ivan; Goodman, Karen J; Geary, Jani; Cromarty, Taylor J; Price, Nancy L; Quilty, Dougla; Corvalan, Alejandro H; Gonzalez, Robinson; Riquelme, Arnoldo; García-Cancino, Apolinaria; Parra-Sepúlveda, Cristian; Castillo, Francisco; Bravo, Maria Mercede; Pazos, Alvaro; Bravo, Luis E; Fox, James G; Ramírez-Mayorga, Vanessa; Molina-Castro, Silvia; Durán-Bermúdez, Sundry; Campos-Núñez, Christian; Chaves-Cervantes, Manuel; Tshibangu-Kabamba, Evariste; Tumba, Ghislain Disashi; Tshimpi-Wola, Antoine; de Jesus Ngoma-Kisoko, Patrick; Tshibangu, Fabien Mbaya; Mukanya, Alain Cimuanga; Nkomba, Tressy Kalenga; Cruz, Modesto; Abreu, José Jiménez; Secka, Ousman; Link, Alexander; Malfertheiner, Peter; Adinortey, Michael Buenor; Bockarie, Ansumana Sandy; Adinortey, Cynthia Ayefoumi; Ofori, Eric Gyamerah; Sgouras, Dionyssios N; Martinez-Gonzalez, Beatriz; Michopoulos, Spyridon; Georgopoulos, Sotirio; Hernandez, Elisa; Dominguez, Ricardo L; Morgan, Douglas R; Harðardóttir, Hjördí; Gunnarsdóttir, Anna Ingibjörg; Guðjónsson, Hallgrímur; Jónasson, Jón Gunnlaugur; Björnsson, Einar S; Ballal, Mamatha; Shetty, Vignesh; Miftahussurur, Muhammad; Sugihartono, Titong; Alfaray, Ricky Indra; Waskito, Langgeng Agung; Fauzia, Kartika Afrida; Syam, Ari Fahrial; Maulahela, Hasan; Malekzadeh, Reza; Peretz, Avi; Azrad, Maya; On, Avi; De Re, Valli; Zanussi, Stefania |
| Publication Year: |
2026 |
| Collection: |
Università degli studi di Trieste: ArTS (Archivio della ricerca di Trieste) |
| Subject Terms: |
Genomic determinants of antibiotic resistance; Helicobacter pylori treatment; phenotypic and genotypic observational study |
| Description: |
Background: Rising antimicrobial resistance of Helicobacter pylori is a public health challenge. Genomic-based susceptibility testing allows for the identification of resistance-associated mutations, complementing conventional diagnostics and advancing towards pathogen-based personalised therapies. Our study aimed to identify genes and mutations involved in antimicrobial resistance in H pylori and evaluate the extent to which these markers can be used as predictors of phenotypic resistance against clarithromycin and levofloxacin. Methods: In this retrospective phenotypic and genotypic observational study, we included 1011 H pylori whole-genome sequences and strains of known geographical origin from the H pylori Genome Project (HpGP) collection. We performed phenotypic clarithromycin and levofloxacin susceptibility testing on a subset of 419 HpGP strains using Etest at a centralised laboratory. A genomic analysis was conducted to identify 23S rRNA and gyrA variants and build a curated catalogue of mutations associated with resistance to clarithromycin (ie, 23S rRNA 2142A→G, 2142A→C, and 2143A→G) and levofloxacin (ie, gyrA A88V or A88P, N87K or N87I, and D91G, D91N, or D91Y). Genotype-phenotype concordance was assessed to estimate sensitivity and specificity, and the curated catalogue of resistance-associated mutations was applied to the complete HpGP set. Region-specific prevalence of resistance-associated mutations was calculated for a combined dataset including the HpGP genomes and 768 whole-genome sequences retrieved from the US National Center for Biotechnology Information Sequence Read Archive repository. Associations between resistance genotypes, H pylori subpopulations, and minimum inhibitory concentrations (MICs) were tested. Findings: Clarithromycin-resistant and levofloxacin-resistant HpGP strains were estimated with a sensitivity and specificity of 100%, with all confidence intervals ranging from 96% to 100%. The combined analysis (n=1779) found the highest prevalence of clarithromycin resistance in ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
ELETTRONICO |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41453373; info:eu-repo/semantics/altIdentifier/wos/WOS:001675331400001; volume:7; issue:1; firstpage:"-"; lastpage:"-"; numberofpages:12; journal:THE LANCET MICROBE; https://hdl.handle.net/11368/3123439; https://www.sciencedirect.com/science/article/pii/S2666524725001454?via=ihub |
| DOI: |
10.1016/j.lanmic.2025.101217 |
| Availability: |
https://hdl.handle.net/11368/3123439; https://doi.org/10.1016/j.lanmic.2025.101217; https://www.sciencedirect.com/science/article/pii/S2666524725001454?via=ihub |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license:Digital Rights Management non definito ; license uri:http://creativecommons.org/licenses/by/4.0/ ; license uri:iris.PRI00 |
| Accession Number: |
edsbas.89893C1A |
| Database: |
BASE |