Multidrug-resistant Mycobacterium tuberculosis strain from Equatorial Guinea detected in Spain.
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ABSTRACT:
SUBMITTER: Gavin P
PROVIDER: S-EPMC2857231 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The rise of drug-resistant strains is a major challenge to containing the tuberculosis (TB) pandemic. Yet, little is known about the extent of resistance in early years of chemotherapy and when transmission of resistant strains on a larger scale became a major public health issue. Here we reconstruct the timeline of the acquisition of antimicrobial resistance during a major ongoing outbreak of multidrug-resistant TB in Argentina. We estimate that the progenitor of the outbreak strain acquired resistance to isoniazid, streptomycin and rifampicin by around 1973, indicating continuous circulation of a multidrug-resistant TB strain for four decades. By around 1979 the strain had acquired additional resistance to three more drugs. Our results indicate that Mycobacterium tuberculosis (Mtb) with extensive resistance profiles circulated 15 years before the outbreak was detected, and about one decade before the earliest documented transmission of Mtb strains with such extensive resistance profiles globally.
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Project description:Multidrug-resistant tuberculosis (MDR-TB) is a significant health problem in Panama. The extent to which such cases are the result of primary or acquired resistance and the strain families involved are unknown. We performed whole-genome sequencing of a collection of 66 clinical MDR isolates, along with 31 drug-susceptible isolates, that were isolated in Panama between 2001 and 2010; 78% of the MDR isolates belong to the Latin American-Mediterranean (LAM) family. Drug resistance mutations correlated well with drug susceptibility profiles. To determine the relationships among these strains and to better understand the acquisition of resistance mutations, a phylogenetic tree was constructed based on a genome-wide single-nucleotide polymorphism analysis. The phylogenetic tree shows that the isolates are highly clustered, with a single strain (LAM9-c1) accounting for nearly one-half of the MDR isolates (29/66 isolates). The LAM9-c1 strain was most prevalent among male patients of working age and was associated with high mortality rates. Members of this cluster all share identical mutations conferring resistance to isoniazid (KatG S315T mutation), rifampin (RpoB S531L mutation), and streptomycin (rrs C517T mutation). This evidence of primary resistance supports a model in which MDR-TB in Panama is driven by clonal expansion and ongoing transmission of several strains in the LAM family, including the highly successful MDR strain LAM9-c1. The phylogenetic analysis also shows that the LAM9-c1 strain is closely related to the KwaZulu-Natal (KZN) extensively drug-resistant TB strain identified in KwaZulu-Natal, South Africa. The LAM9-c1 and KZN strains likely arose from a recent common ancestor that was transmitted between Panama and South Africa and had the capacity to tolerate an accumulation of multiple resistance mutations.
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Project description:A distinct branch of the Mycobacterium tuberculosis W phylogenetic lineage (W14 group) has been identified and characterized by various genotyping techniques. The W14 group comprises three strain variants: W14, W23, and W26, which accounted for 26 clinical isolates from the New York City metropolitan area. The W14 group shares a unique IS6110 hybridizing banding motif as well as distinct polymorphic GC-rich repetitive sequence and variable number tandem repeat patterns. All W14 group members have high levels of streptomycin resistance. When the streptomycin resistance rpsL target gene was sequenced, all members of this strain family had an identical mutation in codon 43. Patients infected with the W14 group were primarily of non- Hispanic black origin (77%); all were US-born. Including HIV positivity, 84% of the patients had at least one known risk factor for tuberculosis.
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Project description:Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10) isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968.
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Project description:BackgroundMolecular mechanisms determining the transmission and prevalence of drug resistant tuberculosis (DR-TB) in Papua New Guinea (PNG) are poorly understood. We used genomic and drug susceptibility data to explore the evolutionary history, temporal acquisition of resistance and transmission dynamics of DR-TB across PNG.MethodsWe performed whole genome sequencing on isolates from Central Public Health Laboratory, PNG, collected 2017-2019. Data analysis was done on a composite dataset that also included 100 genomes previously sequenced from Daru, PNG (2012-2015).ResultsSampled isolates represented 14 of the 22 PNG provinces, the majority (66/94; 70%) came from the National Capital District (NCD). In the composite dataset, 91% of strains were Beijing 2.2.1.1, identified in 13 provinces. Phylogenetic tree of Beijing strains revealed two clades, Daru dominant clade (A) and NCD dominant clade (B). Multi-drug resistance (MDR) was repeatedly and independently acquired, with the first MDR cases in both clades noted to have emerged in the early 1990s, while fluoroquinolone resistance emerged in 2009 (95% highest posterior density 2000-2016). We identified the presence of a frameshift mutation within Rv0678 (p.Asp47fs) which has been suggested to confer resistance to bedaquiline, despite no known exposure to the drug. Overall genomic clustering was significantly associated with rpoC compensatory and inhA promoter mutations (p < 0.001), with high percentage of most genomic clusters (12/14) identified in NCD, reflecting its role as a potential national amplifier.ConclusionsThe acquisition and evolution of drug resistance among the major clades of Beijing strain threaten the success of DR-TB treatment in PNG. With continued transmission of this strain in PNG, genotypic drug resistance surveillance using whole genome sequencing is essential for improved public health response to outbreaks. With occurrence of resistance to newer drugs such as bedaquiline, knowledge of full drug resistance profiles will be important for optimal treatment selection.
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Project description:Multidrug-resistant tuberculosis (MDR-TB) has imposed a significant economic and health burden worldwide, notably in China. Using whole genome sequence, we sought to understand the mutation and transmission of MDR-TB in Shandong. A retrospective study of patients diagnosed with pulmonary tuberculosis in Shandong from 2009 to 2018 was conducted. To explore transmission patterns, we performed whole genome sequencing on MDR-TB isolates, identified genomic clusters, and assessed the drug resistance of TB isolates. Our study analyzed 167 isolates of MDR-TB, finding that 100 were clustered. The predominant lineage among MDR-TB isolates was lineage 2, specifically with a notable 88.6% belonging to lineage 2.2.1. Lineage 4 constituted a smaller proportion, accounting for 4.2% of the isolates. We discovered that Shandong has a significant clustering percentage for MDR-TB, with Jining having the highest percentage among all Shandong cities. The clustering percentages of MDR-TB, pre-extensively drug-resistant tuberculosis, and extensively drug-resistant tuberculosis were 59.9%, 66.0%, and 71.4%, respectively, and the clustering percentages increased with the expansion of the anti-TB spectrum. Isolates from genomic clusters 1 and 3 belonged to lineage 2.2.1 and showed signs of cross-regional transmission. The distribution of rrs A1401G and katG S315T mutations in lineage 2.2.1 and 2.2.2 strains differed significantly (P < .05). MDR-TB isolates with rpoB I480V, embA-12C > T, and rrs A1401G mutations showed a higher likelihood of clustering (P < .05). Our findings indicate a significant problem of local transmission of MDR-TB in Shandong, China. Beijing lineage isolates and some drug-resistant mutations account for the MDR-TB transmission in Shandong.
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Project description:In human tuberculosis (TB), CD8+ T cells contribute to host defense by the release of Th1 cytokines and the direct killing of Mycobacterium tuberculosis (Mtb)-infected macrophages via granule exocytosis pathway or the engagement of receptors on target cells. Previously we demonstrated that strain M, the most prevalent multidrug-resistant (MDR) Mtb strain in Argentine, is a weak inducer of IFN-? and elicits a remarkably low CD8-dependent cytotoxic T cell activity (CTL). In contrast, the closely related strain 410, which caused a unique case of MDR-TB, elicits a CTL response similar to H37Rv. In this work we extend our previous study investigating some parameters that can account for this discrepancy. We evaluated the expressions of the lytic molecules perforin, granzyme B and granulysin and the chemokine CCL5 in CD8+ T cells as well as activation markers CD69 and CD25 and IL-2 expression in CD4+ and CD8+ T cells stimulated with strains H37Rv, M and 410. Our results demonstrate that M-stimulated CD8+ T cells from purified protein derivative positive healthy donors show low intracellular expression of perforin, granzyme B, granulysin and CCL5 together with an impaired ability to form conjugates with autologous M-pulsed macrophages. Besides, M induces low CD69 and IL-2 expression in CD4+ and CD8+ T cells, being CD69 and IL-2 expression closely associated. Furthermore, IL-2 addition enhanced perforin and granulysin expression as well as the degranulation marker CD107 in M-stimulated CD8+ T cells, making no differences with cells stimulated with strains H37Rv or 410. Thus, our results highlight the role of IL-2 in M-induced CTL activity that drives the proper activation of CD8+ T cells as well as CD4+ T cells collaboration.
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Project description:We report the draft genome sequence of Mycobacterium tuberculosis Beijing strain OM-V02_005, which exhibits possible hypertransmissible characteristics among the population of patients with multidrug-resistant tuberculosis in Osaka Prefecture, the largest urban area in western Japan.
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