Evaluation of WHO catalog of mutations and five WGS analysis tools for drug resistance prediction of Mycobacterium tuberculosis isolates from China

Guiqing He; Qingyong Zheng; Jichan Shi; Lianpeng Wu; Bei Huang; Yang Yang

doi:10.1128/spectrum.03341-23

Microbiology Spectrum (Aug 2024)

Evaluation of WHO catalog of mutations and five WGS analysis tools for drug resistance prediction of Mycobacterium tuberculosis isolates from China

Guiqing He,
Qingyong Zheng,
Jichan Shi,
Lianpeng Wu,
Bei Huang,
Yang Yang

Affiliations

Guiqing He: Department of Infectious Diseases, Wenzhou Central Hospital, The Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University, Wenzhou, Zhejiang, China
Qingyong Zheng: Laboratory of Infectious Diseases, Wenzhou Central Hospital, The Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University, Wenzhou, Zhejiang, China
Jichan Shi: Department of Infectious Diseases, Wenzhou Central Hospital, The Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University, Wenzhou, Zhejiang, China
Lianpeng Wu: Department of Clinical Laboratory Medicine, Wenzhou Central Hospital, The Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University, Wenzhou, Zhejiang, China
Bei Huang: Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics and Advanced Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology and College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, Zhejiang, China
Yang Yang: Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics and Advanced Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology and College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, Zhejiang, China

DOI: https://doi.org/10.1128/spectrum.03341-23
Journal volume & issue: Vol. 12, no. 8

Abstract

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ABSTRACT The continuous advancement of molecular diagnostic techniques, particularly whole-genome sequencing (WGS), has greatly facilitated the early diagnosis of drug-resistant tuberculosis patients. Nonetheless, the interpretation of results from various types of mutations in drug-resistant-associated genes has become the primary challenge in the field of molecular drug-resistance diagnostics. In this study, our primary objective is to evaluate the diagnosis accuracy of the World Health Organization (WHO) catalog of mutations and five WGS analysis tools (PhyResSE, Mykrobe, TB Profiler, Gen-TB, and SAM-TB) in drug resistance to 10 anti-Mycobacterium tuberculosis (MTB) drugs. We utilized the data of WGS collected between 2014 and 2017 in Zhejiang Province, consisting of 110 MTB isolates as detailed in our previous study. Based on phenotypic drug susceptibility testing (DST) results using the proportion method on Löwenstein-Jensen medium with antibiotics, we evaluated the predictive accuracy of genotypic DST obtained by these tools. The results revealed that the WHO catalog of mutations and five WGS analysis tools exhibit robust predictive capabilities concerning resistance to isoniazid, rifampicin, ethambutol, streptomycin, amikacin, kanamycin, and capreomycin. Notably, Mykrobe, SAM-TB, and TB Profiler demonstrate the most accurate predictions for resistance to pyrazinamide, prothionamide, and para-aminosalicylic acid, respectively. These findings are poised to significantly guide and influence future clinical treatment strategies and resistance monitoring protocols.IMPORTANCEWhole-genome sequencing (WGS) has the potential for the early diagnosis of drug-resistant tuberculosis. However, the interpretation of mutations of drug-resistant-associated genes represents a significant challenge as the amount and complexity of WGS data. We evaluated the accuracy of the World Health Organization catalog of mutations and five WGS analysis tools in predicting drug resistance to first-line and second-line anti-TB drugs. Our results offer clinicians guidance on selecting appropriate WGS analysis tools for predicting resistance to specific anti-TB drugs.

Published in Microbiology Spectrum

ISSN: 2165-0497 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/spectrum

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