The sensitivity to thiacetazone and para-aminosalicylic acid and the virulence in the guinea pig of East African strains of mycobacterium tuberculosis

Abstract Background: There is a general dearth of information on extrapulmonary tuberculosis (EPTB). Here, we investigated Mycobacterium tuberculosis (Mtb) drug resistance and transmission patterns in EPTB patients treated in the Tshwane metropolitan area, in South Africa.Methods: Consecutive Mtb culture-positive non-pulmonary samples from unique EPTB patients underwent mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. MTBDRplus assay was used to search mutations for isoniazid and rifampin resistance. Machine learning algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and corresponding 95% confidence intervals (CI). Results: Of the 70 isolates examined, the largest cluster comprised 25 (36%) Mtb strains that belonged to the East Asian lineage. East Asian lineage was significantly more likely to occur within chains of transmission when compared to the Euro-American and East-African Indian lineages: OR= 10.11 (95% CI: 1.56-116). Lymphadenitis, meningitis and cutaneous TB, were significantly more likely to be associated with drug resistance: OR=12.69 (95% CI: 1.82-141.60) and AR = 0.25 (95% CI: 0.06-0.43) when compared with other EPTB sites, which suggests that poor rifampin penetration might be a contributing factor.Conclusions: The majority of Mtb strains circulating in the Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages. Each of these are likely to be clustered, suggesting on-going EPTB transmission. Since 25% of the drug resistance was attributable to sanctuary EPTB sites notorious for poor rifampin penetration, we hypothesize that poor anti-tuberculosis drug dosing might have a role in the development of resistance.

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Genetic Diversity ofMycobacterium tuberculosisComplex Isolated from Tuberculosis Patients in Bahir Dar City and Its Surroundings, Northwest Ethiopia

BioMed Research International ◽

10.1155/2015/174732 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Anwar Nuru ◽

Gezahegne Mamo ◽

Adane Worku ◽

Aschalew Admasu ◽

Girmay Medhin ◽

...

Keyword(s):

Genetic Diversity ◽

Mycobacterium Tuberculosis ◽

Northwest Ethiopia ◽

Discriminatory Power ◽

Geographical Region ◽

Zoonotic Potential ◽

Bahir Dar ◽

East African ◽

Tuberculosis Patients

The knowledge of the diversity of strains ofMycobacterium tuberculosiscomplex (MTBC) species in a specific geographical region can contribute to the control of tuberculosis (TB). This study was conducted to identify the MTBC isolates to the species and spoligotype international type (SIT) level by spoligotyping. A total of 168 MTBC isolates were recovered from TB patients, spoligotyped, and their patterns were compared with those of the strains registered in the SITVIT2 database. Of 168 isolates spoligotyped, 89 patterns were identified. Ninety-eight isolates were clustered into 19 strain groups with clustering percentage of 58.3%. Forty-four strains matched the preexisting SITs in the SITVIT2 database. The dominant strains were SIT289, SIT134, and SIT3411, comprising 16.7% (28/168), 7.14% (12/168), and 4.76% (8/168) of the isolates, respectively. Euro-American (51.2%), East-African-Indian (34.5%), andM. africanum(9.52%) were the major lineages identified. Two strains ofM. boviswere isolated from TB lymphadenitis cases. The high percentage of clustered strains ofM. tuberculosiscould suggest that a small number of lineages ofM. tuberculosisare causing the disease in the area while isolation ofM. boviscould suggest its zoonotic potential. Additionally, identification ofM. africanumrequires further confirmation by tools with a better discriminatory power.

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Characterization of Mutations Conferring Extensive Drug Resistance to Mycobacterium tuberculosis Isolates in Pakistan

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05101-11 ◽

2011 ◽

Vol 55 (12) ◽

pp. 5654-5659 ◽

Cited By ~ 31

Author(s):

Asho Ali ◽

Rumina Hasan ◽

Kauser Jabeen ◽

Nusrat Jabeen ◽

Ejaz Qadeer ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Hot Spot ◽

East African ◽

Content Type ◽

Diagnostic Assays ◽

Asian Strain ◽

Central Asian ◽

Extensive Drug Resistance ◽

Detection Of Mutations

ABSTRACTThe increasing incidence of extensively drug-resistant (XDR)Mycobacterium tuberculosisin high-tuberculosis-burden countries further highlights the need for improved rapid diagnostic assays. An increasing incidence of XDRM. tuberculosisstrains in Pakistan has been reported, but drug resistance-associated mutations in these strains have not been evaluated previously. We sequenced the “hot-spot” regions ofrpoB,katG,inhA,ahpC,gyrA,gyrB, andrrsgenes in 50 XDRM. tuberculosisstrains. It was observed that 2% of rifampin, 6% of isoniazid, 24% of fluoroquinolone, and 32% of aminoglycoside/capreomycin resistance in XDRM. tuberculosisstrains would be undetected if only these common hot-spot regions were tested. The frequencies of resistance-conferring mutations were found to be comparable among all XDRM. tuberculosisstrain families present, including the Central Asian Strain, Beijing, and East African Indian genogroups and the Unique isolates. Additional genetic loci need to be tested for detection of mutations conferring fluoroquinolone, aminoglycoside, and capreomycin resistance in order to improve molecular diagnosis of regional XDRM. tuberculosisstrains.

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Proteomics of Culture Filtrate of Prevalent Mycobacterium tuberculosis Strains: 2D-PAGE Map and MALDI-TOF/MS Analysis

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555217717639 ◽

2017 ◽

Vol 22 (9) ◽

pp. 1142-1149 ◽

Cited By ~ 1

Author(s):

Gavish Kumar ◽

Hari Shankar ◽

Divakar Sharma ◽

Prashant Sharma ◽

Deepa Bisht ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Culture Filtrate ◽

Polyacrylamide Gel Electrophoresis ◽

Critical Role ◽

Laboratory Strain ◽

Proteomic Profiling ◽

East African ◽

Mycobacterium Tuberculosis H37rv ◽

Flight Mass Spectrometry ◽

Central Asian

Although diverse efforts have been done to identify biomarkers for control of tuberculosis using laboratory strain Mycobacterium tuberculosis H37Rv, the disease still poses a threat to mankind. There are many emerging M. tuberculosis strains, and proteomic profiling of these strains might be important to find out potential targets for diagnosis and/or prevention of tuberculosis. We evaluated the comparative proteomic profiling of culture filtrate (CF) proteins from prevalent M. tuberculosis strains (Central Asian or Delhi type; CAS1_Del, East African-Indian; EAI-3 and Beijing family) by 2D polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry. As a result, we could identify 12 CF proteins (Rv0066c, Rv1310, Rv3375, Rv1415, Rv0567, Rv1886c, Rv3803c, Rv3804c, Rv2031c, Rv1038c, Rv2809, and Rv1911c), which were consistently increased in all prevalent M. tuberculosis strains, and interestingly, two CF proteins (Rv2809, Rv1911c) were identified with unknown functions. Consistent increased intensity of these proteins suggests their critical role for survival of prevalent M. tuberculosis isolates, and some of these proteins may also have potential as diagnostic and vaccine candidates for tuberculosis, which needs to be further explored by immunological analysis.

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