Genomic-based surveillance reveals high ongoing transmission of multi-drug-resistant Mycobacterium tuberculosis in Southern Brazil

Salvato, Richard Steiner; Reis, Ana Júlia; Schiefelbein, Sun Hee; Gomez, Michael A.; Salvato, Stéphanie Steiner; Silva, Larissa Vitória da; Costa, Elis Regina Dalla; Unis, Gisela; Dias, Claudia; Viveiros, Miguel; Portugal, Isabel; Groll, Andréa von; Silva, Pedro Eduardo Almeida da; Kritski, Afrânio Lineu; Perdigão, João; Rossetti, Maria Lúcia Rosa

doi:10.1016/j.ijantimicag.2021.106401

Cited by 12 publications

(8 citation statements)

References 36 publications

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“…Mutations in katG, kasA, inhA, fabG1 genes and the oxyR-ahpC intergenic region are associated with conferring resistance to isoniazid (44,62,63), thus ethA/R mutations are associated with ethionamide resistance (48,64,65). Our results were in concordance with previous studies (44,63,66) due to the higher prevalence of mutations in katG (88.8%).…”

Section: Discussionmentioning

confidence: 99%

“…A high proportion of STR resistance was observed in this study, which 60.7% of mutations was in the rpsL gene, agreeing that the k43R mutation is the most recurrent streptomycin resistance-associated mutation (32,79,81). In the rrs gene, the substitutions identified at positions 492, 514, 517, 888 and 906 previously have been associated with streptomycin resistance in TB (8,62,82,83); even though the 1401A>G, 1402C>T, and 1484G>T have been associated with cross-resistance to kanamycin, capreomycin or amikacin (84–86), only 1401A>G mutation was presented in 7.1% of isolates. Variations in the promoter (−37G>T, -14C>T, -12C>T, and -10G>A) of the eis gene have been associated with a low resistance to kanamycin (87,88).…”

Section: Discussionmentioning

confidence: 99%

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A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools

Morey-León

Mejía-Ponce

Pardo

et al. 2023

Preprint

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Tuberculosis (TB) is among the most deadly diseases that affect worldwide, its impact is mainly due to the continuous emergence of resistant isolates during treatment due to the laborious process of resistance diagnosis, non-adherence to treatment and circulation of previously resistant isolates ofMycobacterium tuberculosis. The aim in this study was evaluate the performance and functionalities of web-based tools: Mykrobe, TB-profiler, PhyReSse, KvarQ, and SAM-TB for detecting resistance in isolate ofMycobacterium tuberculosisin comparison with conventional drug susceptibility tests. We used 88M. tuberculosisisolates which were drug susceptibility tested and subsequently fully sequenced and web-based tools analysed. Statistical analysis was performed to determine the correlation between genomic and phenotypic analysis. Our data show that the main sub-lineage was LAM (44.3%) followed by X-type (23.0%) within isolates evaluated. Mykrobe has a higher correlation with DST (98% of agreement and 0.941Cohen's Kappa) for global resistance detection, but SAM-TB, PhyReSse and Mykrobe had a better correlation with DST for first-line drug analysis individually. We have identified that 50% of mutations characterised by all web-based tools were canonical inrpoB, katG,embB, pncA, gyrAandrrsregions. Our findings suggest that SAM-TB, PhyReSse and Mykrobe were the web-based tools more efficient to determine canonical resistance-related mutations, however more analysis should be performed to improve second-line detection. The improvement of surveillance programs for the TB isolates applying WGS tools against first line drugs, MDR-TB and XDR-TB are priorities to discern the molecular epidemiology of this disease in the country.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools

Morey-León

Mejía-Ponce

Pardo

et al. 2023

Preprint

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“…Our results indicate that despite the in vitro fitness cost associated with borderline rpoB mutations, strains with such mutations seem to transmit equally well as strains with common rpoB mutations. In a drug-resistant TB cohort in Southern Brazil, 14/22 isolates (63.6%) with a borderline rpoB mutation were found in a cluster, compared to an overall clustering proportion of MDR-TB isolates of 73.4% [28].…”

Section: Discussionmentioning

confidence: 99%

BorderlinerpoBmutations transmit at the same rate as commonrpoBmutations in a tuberculosis cohort in Bangladesh

Lempens

Deun²,

Aung

et al. 2023

Preprint

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The spread of multidrug-resistant tuberculosis (MDR-TB) is a growing problem in many countries worldwide. Resistance to one of the primary first-line drugs, rifampicin, is caused by mutations in the Mycobacterium tuberculosis rpoB gene. While some of these infrequent mutations show lower fitness in vitro than more common mutations, their in vivo fitness is currently unknown. We used a dataset of 394 whole genome sequenced MDR-TB isolates from Bangladesh, representing around 44% of notified MDR-TB cases over 6 years, to look at differences in transmission clustering between isolates with borderline rpoB mutations and those with common rpoB mutations. We found a relatively low percentage of transmission clustering in the dataset (34.8%) but no difference in clustering between different types of rpoB mutations. Compensatory mutations in rpoA, rpoB, and rpoC were associated with higher levels of transmission clustering as were lineages 2, 3, and 4 relative to lineage 1. Young people as well as patients with high sputum smear positive TB were more likely to be in a transmission cluster. Our findings show that although borderline rpoB mutations have lower in vitro growth potential this does not translate into lower transmission potential or in vivo fitness. Proper detection of these mutations is crucial to ensure they do not go unnoticed and spread MDR-TB within communities.

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“…The potential of WGS to provide a quick and comprehensive view of the genotype and reliable prediction of the lineages has been extensively reported [ 5 , 7 , 14 , 40 ]; thus, its application in surveillance programs is necessary. The Euro-American lineage (lineage 4) presents a variable distribution in Argentina with a predominance of M and Ra strains [ 41 ], for Brazil, lineage 4 varies between 25–99% [ 13 , 42 , 43 ], for Colombia, between 85–99% [ 44 – 46 ], for Mexico between 69–98% [ 47 , 48 ] and for Peru around 90% [ 12 , 49 , 50 ]. Ecuador is not an exception, in fact, all the samples analyzed by us belong to the Euro-American lineage.…”

Section: Discussionmentioning

confidence: 99%

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

et al. 2022

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Background Tuberculosis is a serious infectious disease affecting millions of people. In spite of efforts to reduce the disease, increasing antibiotic resistance has contributed to persist in the top 10 causes of death worldwide. In fact, the increased cases of multi (MDR) and extreme drug resistance (XDR) worldwide remains the main challenge for tuberculosis control. Whole genome sequencing is a powerful tool for predicting drug resistance-related variants, studying lineages, tracking transmission, and defining outbreaks. This study presents the identification and characterization of resistant clinical isolates of Mycobacterium tuberculosis including a phylogenetic and molecular resistance profile study by sequencing the complete genome of 24 strains from different provinces of Ecuador. Results Genomic sequencing was used to identify the variants causing resistance. A total of 15/21 isolates were identified as MDR, 4/21 as pre-XDR and 2/21 as XDR, with three isolates discarded due to low quality; the main sub-lineage was LAM (61.9%) and Haarlem (19%) but clades X, T and S were identified. Of the six pre-XDR and XDR strains, it is noteworthy that five come from females; four come from the LAM sub-lineage and two correspond to the X-class sub-lineage. A core genome of 3,750 genes, distributed in 295 subsystems, was determined. Among these, 64 proteins related to virulence and implicated in the pathogenicity of M. tuberculosis and 66 possible pharmacological targets stand out. Most variants result in nonsynonymous amino acid changes and the most frequent genotypes were identified as conferring resistance to rifampicin, isoniazid, ethambutol, para-aminosalicylic acid and streptomycin. However, an increase in the resistance to fluoroquinolones was detected. Conclusion This work shows for the first time the variability of circulating resistant strains between men and women in Ecuador, highlighting the usefulness of genomic sequencing for the identification of emerging resistance. In this regard, we found an increase in fluoroquinolone resistance. Further sampling effort is needed to determine the total variability and associations with the metadata obtained to generate better health policies.

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Genomic-based surveillance reveals high ongoing transmission of multi-drug-resistant Mycobacterium tuberculosis in Southern Brazil

Cited by 12 publications

References 36 publications

A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools

A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools

BorderlinerpoBmutations transmit at the same rate as commonrpoBmutations in a tuberculosis cohort in Bangladesh

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

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