Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola

Rando‐Segura, Ariadna; Aznar, María Luisa; Moreno, María Milagros; Soley, Mateu Espasa; Igual, Elena Sulleiro; García, Cristina Bocanegra; Olivas, Eva Gil; Eugénio, Arlete N.E.; Huesca, Carlos Escartin; Zacarias, Adriano; Collado, Josep Vegue; Katimba, Domingos; Cano, Maria Carmen Vivas; Étienne, Gabriel; García, Maria Teresa López; Suñé, Tomás Pumarola; Romero, Israel Molina; Fernández, María Teresa

doi:10.1186/s12879-021-06763-8

Cited by 9 publications

(5 citation statements)

References 29 publications

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“…Although in less frequency, the second most common mutation D516V (14.8%) in this study was previously reported in Ethiopia, 19 , 20 India 28 and Sudan. 23 However, higher or similar proportion to our findings was reported in Angola (17.2%), 29 India (17.7%), 24 China (10.1%) 27 and Ecuador (28.6%). 30 Eleven isolates (12.5%) showed mutations at codon 526 in which 9.1% were at H526Y and 3.4% at H526D.…”

Section: Discussionsupporting

confidence: 89%

Profile and Frequency of Mutations Conferring Drug-Resistant Tuberculosis in the Central, Southeastern and Eastern Ethiopia

Agonafir¹,

Belay²,

Feleke³

et al. 2023

IDR

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Purpose Advances in molecular tools that assess genes harboring drug resistance mutations have greatly improved the detection and treatment of drug-resistant tuberculosis (DR-TB). This study was conducted to determine the frequency and type of mutations that are responsible for resistance to rifampicin (RIF), isoniazid (INH), fluoroquinolones (FLQs) and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis (MTB) isolates obtained from culture-positive pulmonary tuberculosis (TB) patients in the central, southeastern and eastern Ethiopia. Patients and Methods In total, 224 stored culture-positive MTB isolates from pulmonary TB patients referred to Adama and Harar regional TB laboratories between August 2018 and January 2019 were assessed for mutations conferring RIF, INH, FLQs and SLIDs resistance using GenoType ® MTBDRplus (MTBDRplus) and GenoType ® MTBDRsl (MTBDRsl). Results RIF, INH, FLQs and SLIDs resistance-conferring mutations were identified in 88/224 (39.3%), 85/224 (38.0%), 7/77 (9.1%), and 3/77% (3.9%) of MTB isolates, respectively. Mutation codons rpoB S531L (59.1%) for RIF, katG S315T (96.5%) for INH, gyrA A90V (42.1%) for FLQs and WT1 rrs (100%) for SLIDs were observed in the majority of the isolates tested. Over a 10th of rpoB mutations detected in the current study were unknown. Conclusion In this study, the most common mutations conferring drug resistance to RIF, INH, FLQs were identified. However, a significant proportion of RIF-resistant isolates manifested unknown rpoB mutations. Similarly, although few in number, all SLID-resistant isolates had unknown rrs mutations. To further elucidate the entire spectrum of mutations, tool such as whole-genome sequencing is imperative. Furthermore, the expansion of molecular drug susceptibility testing services is critical for tailoring patient treatment and preventing disease transmission.

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Section: Discussionsupporting

confidence: 89%

Profile and Frequency of Mutations Conferring Drug-Resistant Tuberculosis in the Central, Southeastern and Eastern Ethiopia

Agonafir¹,

Belay²,

Feleke³

et al. 2023

IDR

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“…In 4% (7/175) and 2.6% (6/228) of the cases, the rifampicin-and isoniazid-resistant clinical isolates did not reveal any mutations in the rpoB and katG, fabG-inhA, oxyR-ahpC genes, respectively. The absence of mutations in specific drug-resistant genes has been recorded in 2.3-10.38% of cases in various studies [36][37][38][39]. Mutations in other genes may cause resistance to ant i-TB drugs in these resistant isolates.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Beijing Central Asian/Russian Cluster 94-32 among Multidrug-Resistant M. tuberculosis in Kazakhstan

Akhmetova,

Bismilda,

Chingissova

et al. 2023

Antibiotics

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The Beijing genotype is the most distributed M. tuberculosis family in Kazakhstan. In this study, we identified dominant Beijing clusters in Kazakhstan and assessed their drug susceptibility profiles and association with the most widely spread mutation Ser531Leu of the rpoB gene and the mutation Ser315Thr of the katG gene associated with resistance to rifampicin and isoniazid, respectively. M. tuberculosis isolates (n = 540) from new TB cases were included in the study. MIRU-VNTR genotyping was performed for 540 clinical isolates to determine M. tuberculosis families using 24 loci. RD analysis was additionally performed for the Beijing isolates. The identification of mutations in the drug-resistance genes of M. tuberculosis was performed with allele-specific real-time PCR and Sanger sequencing. The Beijing genotype was identified in 60% (324/540) of the clinical isolates. Central Asian/Russian cluster 94-32 was the most distributed cluster among the Beijing isolates (50.3%; 163/324). Three other dominant Beijing clusters were identified as 94-33 (3.4%; 11/324), 100-32 (3.1%; 10/324) and 99-32 (3.1%; 10/324). The Beijing genotype was associated with drug-resistant TB (p < 0.0001), including multidrug-resistant TB (p < 0.0001), in our study. An association of the mutation Ser531Leu of the rpoB gene with the Beijing genotype was found (p < 0.0001; OR = 16.0000; 95%CI: 4.9161–52.0740). Among the Beijing isolates, cluster 94-32 showed an association with MDR-TB (p = 0.021). This is why the evaluation of the Beijing genotype and its clusters is needed to control MDR-TB in Kazakhstan.

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“…Similar to our results, H445>N was also reported as a discordant mutation ( 9 , 35 , 39 , 41 ). A more recent study ( 42 ) reported that H445>L, D435>Y, and L452>P are involved in a low level of RIF resistance (MIC 0.5–1.0 µg/mL), whereas H445>N and L430>P lower MICs 0.25–0.5 µg/mL under the epidemiological cutoff (MIC 0.125 µg/mL). H445>L is also discordant ( 9 , 15 , 35 , 36 , 41 ), and only one out of nine (11.1%) was MGIT-resistant; however, all nine isolates were LJ-resistant.…”

Section: Discussionmentioning

confidence: 99%

Phenotype versus genotype discordant rifampicin susceptibility testing in tuberculosis: implications for a diagnostic accuracy

Qadir,

Faryal,

Khan

et al. 2024

Microbiol Spectr

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The World Health Organization recommends culture-based techniques as the gold standard for rifampicin-resistant (RR) tuberculosis. However, as rapid molecular assays are rolled out, discordance in resistance has been observed. The current study compared 516 clinical isolates on Lowenstein–Jenson (LJ) and Mycobacteria Growth Indicator Tube (MGIT) drug susceptibility testings (DSTs) with rpoB sequencing. The discordance rate was higher in MGIT DST (24%) compared to LJ (9.4%). We report discordant results for RpoB mutations 430P (MGIT: 14/20; LJ: 19/20), 435Y (MGIT: 5/21; LJ: 17/21), 445N (MGIT: 11/18; LJ: 15/18), 445L (MGIT: 0/9; LJ: 8/9), 452P (MGIT: 5/20; LJ: 17/20), and 445C (MGIT: 1/6; LJ: 2/6) on LJ and MGIT DSTs, respectively. Mutations N438K and T444A, sensitive on LJ and MGIT DSTs, are novel. Two novel discordant mutations, Q436H+N437del and S428I, were also detected. One novel large deletion (Del) ggaccagaacaacccg/G (Del of DQNNP at positions 435–439) demonstrated concordance on LJ and MGIT DST. Numerous double and triple mutations including some novel combinations, M434V+H445N, L430R+D435Y, H445N+S450W, S428R+L430P, M434L+H445N, D435G+A451V, and M434I+D435G+A451V, have also shown higher discordant results on MGIT DST. The discordance results of RR are higher in MGIT DST compared to LJ. We suggest that the genotypic result should be preferred instead of phenotypic DST in case of discordant mutations. Physicians should be aware of such discordance to prescribe an effective treatment. Untargeted whole-genome sequencing to capture MGIT-sensitive and large deletions may be reconsidered for better treatment outcomes in high-burden countries. IMPORTANCE An accurate diagnosis of drug resistance in clinical isolates is an important step for better treatment outcomes. The current study observed a higher discordance rate of rifampicin resistance on Mycobacteria Growth Indicator Tube (MGIT) drug susceptibility testing (DST) than Lowenstein–Jenson (LJ) DST when compared with the rpoB sequencing. We detected a few novel mutations and their combination in rifampicin resistance isolates that were missed by MGIT DST and may be useful for the better management of tuberculosis (TB) treatment outcomes. Few novel deletions in clinical isolates necessitate the importance of rpoB sequencing in large data sets in geographic-specific locations, especially high-burden countries. We explored the discordance rate on MGIT and LJ, which is important for the clinical management of rifampicin resistance to avoid the mistreatment of drug-resistant TB. Furthermore, MGIT-sensitive isolates may be subjected to molecular methods of diagnosis for further confirmation and treatment options.

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Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola

Cited by 9 publications

References 29 publications

Profile and Frequency of Mutations Conferring Drug-Resistant Tuberculosis in the Central, Southeastern and Eastern Ethiopia

Profile and Frequency of Mutations Conferring Drug-Resistant Tuberculosis in the Central, Southeastern and Eastern Ethiopia

Prevalence of Beijing Central Asian/Russian Cluster 94-32 among Multidrug-Resistant M. tuberculosis in Kazakhstan

Phenotype versus genotype discordant rifampicin susceptibility testing in tuberculosis: implications for a diagnostic accuracy

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