title: Mixed Infections and Rifampin Heteroresistance among Mycobacterium tuberculosis Clinical Isolates.
abstract: Mixed infections and heteroresistance of Mycobacterium tuberculosis contribute to the difficulty of diagnosis, treatment, and control of tuberculosis. However, there is still no proper solution for these issues. This study aimed to investigate the potential relationship between mixed infections and heteroresistance and to determine the high-risk groups related to these factors. A total of 499 resistant and susceptible isolates were subjected to spoligotyping and 24-locus variable-number tandem repeat methods to analyze their genotypic lineages and the occurrence of mixed infections. Two hundred ninety-two randomly selected isolates were sequenced on their rpoB gene to examine mutations and heteroresistance. The results showed that 12 patients had mixed infections, and the corresponding isolates belonged to Manu2 (n = 8), Beijing (n = 2), T (n = 1), and unknown (n = 1) lineages. Manu2 was found to be significantly associated with mixed infections (odds ratio, 47.72; confidence interval, 9.68 to 235.23; P < 0.01). Four isolates (1.37%) were confirmed to be heteroresistant, which was caused by mixed infections in three (75%) isolates; these belonged to Manu2. Additionally, 3.8% of the rifampin-resistant isolates showing no mutation in the rpoB gene were significantly associated with mixed infections (χ(2), 56.78; P < 0.01). This study revealed for the first time that Manu2 was the predominant group in the cases of mixed infections, and this might be the main reason for heteroresistance and a possible mechanism for isolates without any mutation in the rpoB gene to become rifampin resistant. Further studies should focus on this lineage to clarify its relevance to mixed infections.
authors.affiliation: Key Laboratory of Bio-Resources and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Bio-Resources and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Bio-Resources and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Zhongyue
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Key Laboratory of Bio-Resources and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Pi
authors.affiliation: Key Laboratory of Bio-Resources and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Honghu
authors.identifier: http://orcid.org/0000-0002-1418-2007
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Laboratory of Bio-Resources and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.affiliation: Chengdu Public Health Clinical Center, Chengdu, Sichuan, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Li
authors.affiliation: WHO Supranational TB Reference Laboratory, Unité de la Tuberculose et des Mycobactéries, Institut Pasteur de Guadeloupe, Abymes Cedex, Guadeloupe, France.
authors.forename: David
authors.initials: D
authors.lastname: Couvin
authors.affiliation: WHO Supranational TB Reference Laboratory, Unité de la Tuberculose et des Mycobactéries, Institut Pasteur de Guadeloupe, Abymes Cedex, Guadeloupe, France.
authors.forename: Nalin
authors.initials: N
authors.lastname: Rastogi
authors.affiliation: Key Laboratory of Bio-Resources and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, People's Republic of China qunsun@scu.edu.cn.
authors.forename: Qun
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D060085:Coinfection / Q000453:epidemiology / Q000382:microbiology*; D003430:Cross-Sectional Studies; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D012189:Retrospective Studies; D012293:Rifampin / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D012293:Rifampin