Genotypic characterization of multi-drug-resistant Mycobacterium tuberculosis isolates in Myanmar

Aye, Khin Saw; Nakajima, Chie; Yamaguchi, Tomoyuki; Win, Min; Shwe, Mu Mu; Win, Aye Aye; Lwin, Thandar; Nyunt, Wint Wint; Ti, Ti; Suzuki, Yasuhiko

doi:10.1016/j.jiac.2015.12.009

Cited by 23 publications

(14 citation statements)

References 25 publications

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“…Of particular interest, a vast majority of isolates showed a Ser to Thr (AGC → ACC) substitution at codon 315 (63.0%). This is consistent with the results reported previously (18,19). We also detected mutations at codons 315, 431, and 439 of katG in one isolate, meanwhile, the Thr271 → Ala (ACT → GCT) substitution was detected in another isolate.…”

Section: Discussionsupporting

confidence: 93%

“…We only detected a single mutation at codon 3 in one (1.1%) isolate, codon 21 in three (3.3%) isolates, and codon 94 in one (1.1%) isolate and their amino acid substitutions were synonymous mutation (GGA → GGC), Ile21 → Thr (ATC → ACC), and Ser94 → Ala (TCG → GCG), respectively. It is worth noting that we did not detect the common frequent mutation (C-15T) in the inhA gene while this mutation was reported in phenotypically resistant isolates in many countries such as Myanmar, the Kyrgyz Republic, and Ecuador (18,19,21). It might be related to regional differences.…”

Section: Discussionmentioning

confidence: 54%

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Genotypic Characterization of katG, inhA, and ahpC in Isoniazid-Resistant Mycobacterium tuberculosis Clinical Isolates in Shanghai, China

Cao

Zhan

Guo

et al. 2020

Jundishapur J Microbiol

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Background: Mycobacterium tuberculosis is a pathogen that causes Tuberculosis and can invade various organs in infected patients. Its high morbidity and high mortality seriously threaten human health. In recent years, the continuous emergence of drug-resistant Tuberculosis bacteria has brought severe challenges to the prevention and control of Tuberculosis. Objectives: This study aimed to characterize the most frequent mutations of the katG, inhA, and ahpC genes in isoniazid (INH)resistant M. tuberculosis clinical isolates in Shanghai Pulmonary Hospital, China, and investigate the relationship between gene mutations and the minimum inhibitory concentrations (MICs) of INH against M. tuberculosis. Methods: We collected 92 INH-resistant and 30 INH-susceptible clinical isolates of M. tuberculosis. The drug resistance profiles of M. tuberculosis clinical isolates against common anti-tuberculosis drugs were determined and sequencing analysis was performed. Results: Of 92 INH-resistant strains, mutations in the katG and inhA genes were observed in 64 (69.6%) isolates and five (5.4%) isolates, respectively, and only had one (1.1%) strain both katG and inhA mutations. Among them, 62 (67.4%) strains carried a single mutation at codon 315 of the katG gene and a new mutation site was found in the katG gene of two strains. We detected a single mutation site at codon 271 and three simultaneous mutation sites at codons 315, 431, and 439. Only one (3.3%) of the 30 isoniazid-sensitive strains had the katG mutation. The AhpC mutation was detected in no experimental strains. The KatG Ser 315 Thr (AGC315ACC) mutation occurred in 53 (68.8%) out of 77 strains with high MICs (≥ 1 g/mL) of isoniazid-resistant M. tuberculosis while five (33.3%) out of 15 strains with low MICs (less than 1 g/mL) had katG Ser 315 Thr (AGC315ACC) mutation. Conclusions: Isoniazid-resistant strains were dominated by Ser315 → Thr (AGC → ACC) substitution, which seems to be associated with multidrug resistance and high-level resistance to INH. Multisite mutations are related to multidrug-resistant M. tuberculosis and the discovery of new mutation sites provides a new basis for the detection of drug-resistant M. tuberculosis.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 54%

Genotypic Characterization of katG, inhA, and ahpC in Isoniazid-Resistant Mycobacterium tuberculosis Clinical Isolates in Shanghai, China

Cao

Zhan

Guo

et al. 2020

Jundishapur J Microbiol

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“…A previous report found a high prevalence of the katG S315T gene mutation among HR-TB/MDR-TB/XDR-TB strains (58.7%-68.6%) in Thailand. 16,17 The prevalence of katG S315T varied according to the geographic region: Southeast Asia (78.4%), 18 Vietnam (85.3%), 19 Myanmar (61.2%), 20 Taiwan (29.3%), 6 Japan (25%), 10 India (67.6%), 21 Sri Lanka (67.8%), 22 Romania (52.8%), 23 Cameroon (64%), 24 and the United States (38%). 8 The different ranges of MIC found for each mutation gene can be explained by gene variation.…”

Section: Discussionmentioning

confidence: 99%

<p>Association Between the Phenotype and Genotype of Isoniazid Resistance Among <em>Mycobacterium tuberculosis</em> Isolates in Thailand</p>

Charoenpak¹,

Santimaleeworagun²,

Suwanpimolkul³

et al. 2020

IDR

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Purpose: The emergence of isoniazid-resistant tuberculosis (HR-TB) is a global public health problem, causing treatment failure and high mortality rates. This study aimed to determine the minimal inhibitory concentration (MIC) of isoniazid and detect the gene mutation in HR-TB and any association between the level of isoniazid resistance and gene mutation. Methods: We collected 74 clinical HR-TB isolates from two tertiary-care centers in Thailand. MICs were established using broth macrodilution. A line probe assay (LPA) was used to detect gene mutations that confer resistance to isoniazid, rifampicin, aminoglycosides, and fluoroquinolones. Results: Sixty-one (82.4%) isolates were monoresistant to isoniazid and 44 (72.1%) were highly resistant to isoniazid. From the clinical isolates, the range of isoniazid MICs was 0.4-16 μg/mL. The katG S315T gene mutation was the prominent mutation in both isoniazid-monoresistant TB (70.5%) and multidrug-resistant TB (72.7%) isolates. The positive predictive value (PPV) of katG was 100% in detecting high levels of isoniazid resistance. The PPV of the inhA mutation was 93.8% in detecting low levels of isoniazid resistance. Five isolates (6.8%) exhibited low-level phenotypic resistance, whereas an LPA failed to detect an isoniazid gene mutation. Our study found one HR-TB isolate with a gyrA fluoroquinoloneresistant gene mutation. Conclusion: Most HR-TB isolates had high isoniazid-resistance levels associated with the katG gene mutation. High-dose isoniazid should be used with caution in patients with HR-TB. Early detection of drug resistance by genotypic assay can help determine an appropriate regimen.

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“…Las mutaciones en los genes de Mycobacterium tuberculosis katG e inhA, han sido reportados como los responsables del 60 -80% de los aislados resistentes a isoniacida [27][28][29][30] .…”

Section: Discussionunclassified

Determinación de la mutación S315T del gen katG en aislados resistentes a Isoniacida de Mycobacterium tuberculosis mediante PCR-RFLP

Sánchez-Domínguez

Nicola-Salas

Morey-León

2018

Infect

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Cómo citar este artículo: J. Sánchez-Domínguez, et al. Determinación de la mutación S315T del gen katG en aislados resistentes a Isoniacida de Mycobacterium tuberculosis mediante PCR-RFLP. Infectio 2018; 22(4): 178-184 ResumenObjetivo: determinar la mutación S315T del gen katG en aislados de Mycobacterium tuberculosis resistentes a isoniacida mediante la técnica PCR-RFLP. Materiales y métodos: A partir de 68 aislados de Mycobacterium tuberculosis se realizó el análisis de polimorfismo en productos de amplificación de 1054 y 630 pb que contenían la mutación S315T del gen katG mediante PCR-RFLP empleando las enzimas de restricción MspI y SatI. Mediante SPSS se determinó sensibilidad, especificidad, valores predictivo positivo y negativo, coeficientes de probabilidad positivo y negativo. Resultados: El 74,46% de aislados fenotípicamente resistentes y 4,76% fenotípicamente sensibles presentaron la mutación del gen katG S315T. La PCR-RFLP para S315T del gen katG presentó 85,4% de sensibilidad y 95,2% de especificidad con MspI y 85,4% de sensibilidad y 94,4% de especificidad con SatI. Discusión: La PCR-RFLP tiene una alta capacidad resolutiva que depende de la enzima que se emplee como se observó en estudios previos. La presencia de la mutación S315T en pacientes vírgenes al tratamiento sugiere la circulación de aislados resistentes a Isoniacida. Conclusión: La PCR-RFLP resultó una alternativa válida y rápida para el diagnóstico de la resistencia a isoniacida, mediante la detección de la mutación S315T del gen katG en comparación con el método convencional de las proporciones.Palabras Clave: Mutaciones, Polimorfismo, Isoniacida, PCR-RFLP, Mycobacterium tuberculosis, katG. Determination of S315T mutation within the katG gene in isoniazid-resistant Mycobacterium tuberculosis isolate by PCR-RFLP AbstractObjetive: To determine the S315T mutation of the katG gene in Mycobacterium tuberculosis isoniazid-resistant isolates by PCR-RFLP. Materials and Methods: Polymorphism analysis of 1054 and 630 bp products containing the S315T mutation of the katG gene was performed by PCR-RFLP using the MspI and SatI restriction enzymes from 68 Mycobacterium tuberculosis isolates. Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratio were determined using SPSS. Results: 74.46% of isoniazid-resistant and 4.76% of isoniazid-sensitive isolates showed the S315T mutation in katG gene. The PCR-RFLP for S315T of the katG gene had 85.4% sensitivity and 95.2% specificity with MspI and 85.4% sensitivity and 94.4% specificity with SatI. Discussion: The PCR-RFLP has a high resolutive capacity that depends on the enzyme that is used as it was observed in previous studies. The presence of the S315T mutation in treatment-naive patients suggests the circulation of isolates resistant to isoniazid. Conclusion: PCR-RFLP is a valid and rapid alternative for the diagnosis of isoniazid resistance, by detection of S315T mutation in the katG gene compared to the conventional method of proportions.

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Genotypic characterization of multi-drug-resistant Mycobacterium tuberculosis isolates in Myanmar

Abstract: 25The number of multi-drug-resistant tuberculosis (MDR-TB) cases is rising worldwide. As a 26 countermeasure against this situation, the implementation of rapid molecular tests to identify MDR-27 TB would be effective. To develop such tests, information on the frequency and distribution of

Cited by 23 publications

References 25 publications

Genotypic Characterization of katG, inhA, and ahpC in Isoniazid-Resistant Mycobacterium tuberculosis Clinical Isolates in Shanghai, China

Genotypic Characterization of katG, inhA, and ahpC in Isoniazid-Resistant Mycobacterium tuberculosis Clinical Isolates in Shanghai, China

<p>Association Between the Phenotype and Genotype of Isoniazid Resistance Among <em>Mycobacterium tuberculosis</em> Isolates in Thailand</p>

Determinación de la mutación S315T del gen katG en aislados resistentes a Isoniacida de Mycobacterium tuberculosis mediante PCR-RFLP

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