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Mycobacterium tuberculosis Complex Lineage 3 as Causative Agent of Pulmonary Tuberculosis, Eastern Sudan¹.

ABSTRACT: Pathogen-based factors associated with tuberculosis (TB) in eastern Sudan are not well defined. We investigated genetic diversity, drug resistance, and possible transmission clusters of Mycobacterium tuberculosis complex (MTBC) strains by using a genomic epidemiology approach. We collected 383 sputum specimens at 3 hospitals in 2014 and 2016 from patients with symptoms suggestive of TB; of these, 171 grew MTBC strains. Whole-genome sequencing could be performed on 166 MTBC strains; phylogenetic classification revealed that most (73.4%; n = 122) belonged to lineage 3 (L3). Genome-based cluster analysis showed that 76 strains (45.9%) were grouped into 29 molecular clusters, comprising 2-8 strains/patients. Of the strains investigated, 9.0% (15/166) were multidrug resistant (MDR); 10 MDR MTBC strains were linked to 1 large MDR transmission network. Our findings indicate that L3 strains are the main causative agent of TB in eastern Sudan; MDR TB is caused mainly by transmission of MDR L3 strains.

SUBMITTER: Shuaib YA

PROVIDER: S-EPMC7045825 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTuberculosis (TB) and drug-resistant TB (DR-TB) continue to persist as a serious public health challenges in Ghana. Although several research has evaluated the drug resistance of Mycobacterium tuberculosis complex (MTBc) strains across the country, there is a paucity of data on its magnitude as well as the various lineages circulating in the Eastern region of Ghana.ObjectiveThis study therefore evaluated the distribution of the various lineages of MTBc in the Eastern region of the country and the associated drug resistance.Materials and methodsOne hundred and forty-three (143) patients with pulmonary TB attending the Eastern Regional Hospital, Koforidua/Ghana were included in the study. The BACTEC MGIT 960 tube media was used for both sputum culture and drug susceptibility of streptomycin (STR), isoniazid (INH), rifampicin (RIF) and Ethambutol (ETH). Isolates were initially typed using IS6110, followed by large sequence polymorphisms analysis and spoligotyping.ResultsThe majority [108 (75.5%)] of the 143 patients were male gender and the 45-54 years [46 (32.2%)] age range had the highest frequency. Forty-one (28.7%) of the 143 isolates were IS6110 negative. Of the 102 spoligotyped isolates, the main sub-lineages included 45 (44.1%) Cameroon and 23 (22.5%) Ghana. SITs 61 and 53 represented the major cluster with 22/102 (21.6%) and 13/102 (12.7%) isolates respectively, while 59/65 (90.8%) isolates belonged to Lineage 4 with 27/65 (41.5%) LAM10_CAM. MDR-TB occurred in 26/79 (32.9%) isolates, and was not associated with neither gender [20/58 (34.5%) male vs 6/21 (28.6%) female, OR = 1.31; 95%CI, 0.44-3.92; p = 0.624)] nor age. No association was found between MDR-TB and the major sub-lineages [8/25 (32%) Cameroon (OR = 0.94; 95%CI, 0.34-2.59; p = 0.920) and 5/11 (45.5%) Ghana (OR = 1.87; 95%CI, 0.51-6.80; p = 0.489)], or previously treated [8/23 (34.8%), OR = 0.89; 95%CI, 0.32-2.48; p = 0.823)] patients.ConclusionDespite the serious threat posed by MDR in the study area, no sub-lineage was shown to be associated with drug resistance. Nonetheless, a sustained surveillance of drug resistance pattern is advocated. A lower proportion of M. africanum was observed in the Eastern region of Ghana and will require further evaluation.

Project description:BACKGROUND: Mycobacterium ulcerans is an unusual bacterial pathogen with elusive origins. While closely related to the aquatic dwelling M. marinum, M. ulcerans has evolved the ability to produce the immunosuppressive polyketide toxin mycolactone and cause the neglected tropical disease Buruli ulcer. Other mycolactone-producing mycobacteria (MPM) have been identified in fish and frogs and given distinct species designations (M. pseudoshottsii, M. shinshuense, M. liflandii and M. marinum), however the evolution of M. ulcerans and its relationship to other MPM has not been defined. Here we report the comparative analysis of whole genome sequences from 30 MPM and five M. marinum. RESULTS: A high-resolution phylogeny based on genome-wide single nucleotide polymorphisms (SNPs) showed that M. ulcerans and all other MPM represent a single clonal group that evolved from a common M. marinum progenitor. The emergence of the MPM was driven by the acquisition of the pMUM plasmid encoding genes for the biosynthesis of mycolactones. This change was accompanied by the loss of at least 185 genes, with a significant overrepresentation of genes associated with cell wall functions. Cell wall associated genes also showed evidence of substantial adaptive selection, suggesting cell wall remodeling has been critical for the survival of MPM. Fine-grain analysis of the MPM complex revealed at least three distinct lineages, one of which comprised a highly clonal group, responsible for Buruli ulcer in Africa and Australia. This indicates relatively recent transfer of M. ulcerans between these continents, which represent the vast majority of the global Buruli ulcer burden. Our data provide SNPs and gene sequences that can differentiate M. ulcerans lineages, suitable for use in the diagnosis and surveillance of Buruli ulcer. CONCLUSIONS: M. ulcerans and all mycolactone-producing mycobacteria are specialized variants of a common Mycobacterium marinum progenitor that have adapted to live in restricted environments. Examination of genes lost or retained and now under selective pressure suggests these environments might be aerobic, and extracellular, where slow growth, production of an immune suppressor, cell wall remodeling, loss or modification of cell wall antigens, and biofilm-forming ability provide a survival advantage. These insights will guide our efforts to find the elusive reservoir(s) of M. ulcerans and to understand transmission of Buruli ulcer.

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Mycobacterium tuberculosis Complex Lineage 3 as Causative Agent of Pulmonary Tuberculosis, Eastern Sudan¹.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Mycobacterium tuberculosis Complex Lineage 3 as Causative Agent of Pulmonary Tuberculosis, Eastern Sudan1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Mycobacterium tuberculosis Complex Lineage 3 as Causative Agent of Pulmonary Tuberculosis, Eastern Sudan¹.