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Liang Q.-F.,U.S. Center for Disease Control and Prevention | Pang Y.,National Center for Tuberculosis Control and Prevention | Chen Q.-Y.,U.S. Center for Disease Control and Prevention | Lin S.-F.,U.S. Center for Disease Control and Prevention | And 6 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2013

SETTING: The Fujian District in China has a high migrant worker population. Although tuberculosis (TB) among migrants is a serious threat to public health in Fujian, little is known about the molecular characteristics of TB isolates in this population. OBJECTIVE: To investigate the genetic profile of TB among the migrant population in Fujian. RESULTS: Our study enrolled 243 pulmonary TB patients registered in Fujian. Our data demonstrated that the Beijing genotype was the most common genotype in Fujian, and that the proportion of migrants with the Beijing genotype was significantly higher than that of permanent residents. Furthermore, the population structure of Mycobacterium tuberculosis strains in Fujian was diverse, with no difference in the distribution of mycobacterial interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) subgroups between the migrant and permanent populations. In addition, the discriminatory power of MIRU-VNTR in this study was higher than that found in other regions of China, possibly due to the high percentage of migrants in Fujian. CONCLUSION: The Beijing genotype was the predominant genotype in Fujian. TB strains isolated from this migrant population revealed a genetic profile similar to that of the permanent population. Improvement in public medical and insurance programmes for migrants might be crucial in the effective control of TB in Fujian. © 2013 The Union.


Hong Y.,Anhui University of Science and Technology | Zhou X.,Anhui University of Science and Technology | Fang H.,Anhui University of Science and Technology | Yu D.,Anhui University of Science and Technology | And 2 more authors.
Tuberculosis | Year: 2013

Dormancy of Mycobacterium tuberculosis is likely to be a major cause of extended chemotherapeutic regimens and wide prevalence of tuberculosis. The molecular mechanisms underlying M tuberculosis dormancy are not well understood. In this study, single-copy genes responsible for synthesis (dgc) and degradation (pde) of the ubiquitous bacterial second messenger, cyclic di-GMP (c-di-GMP), were deleted in the virulent M tuberculosis strain H37Rv to generate dgcmut and Δpde, respectively. Under aerobic growth conditions, the two mutants and wild-type cells showed similar phenotypes. However, dgcmut and Δpde exhibited increased and reduced dormancy, respectively, in both anaerobiosis-triggered and vitamin C-triggered in vitro dormancy models, as determined by survival and growth recovery from dormancy. The transcriptomes of aerobic cultures of dgcmut and wild-type H37Rv exhibited no difference, whereas those of anaerobic cultures showed a significant difference with 61 genes that are not a part of the dosR regulon. Furthermore, Δpde but not dgcmut showed decreased infectivity with human THP-1 cells. Δpde also showed attenuated pathogenicity in a C57BL/6 mouse infection model. These findings are explained by c-di-GMP-mediated signaling negatively regulating M tuberculosis dormancy and pathogenicity. © 2013 Elsevier Ltd. All rights reserved.


Kong F.,University of Sydney | Wang H.,Tianjin Medical University | Zhang E.,Capital Medical University | Sintchenko V.,University of Sydney | And 4 more authors.
Journal of Clinical Microbiology | Year: 2010

Sequence analysis of the Nocardia essential secretory protein SecA1 gene (secA1) for species identification of 120 American Type Culture Collection (ATCC) and clinical isolates of Nocardia (16 species) was studied in comparison with 5′-end 606-bp 16S rRNA gene sequencing. Species determination by both methods was concordant for all 10 ATCC strains. secA1 gene sequencing provided the same species identification as 16S rRNA gene analysis for 94/110 (85.5%) clinical isolates. However, 40 (42.6%) isolates had sequences with <99.0% similarity to archived secA1 sequences for the species, including 29 Nocardia cyriacigeorgica (96.6 to 98.9% similarity) and 4 Nocardia veterana (91.5 to 98.9% similarity) strains. Discrepant species identification was obtained for 16 (14.5%) clinical isolates, including 13/23 Nocardia nova strains (identified as various Nocardia species by secA1 sequencing) and 1 isolate each of Nocardia abscessus (identified as Nocardia asiatica), Nocardia elegans (Nocardia africana), and Nocardia transvalensis (Nocardia blacklockiae); both secA1 gene sequence analysis and deduced amino acid sequence analysis determined the species to be different from those assigned by 16S rRNA gene sequencing. The secA1 locus showed high sequence diversity (66 sequence or genetic types versus 40 16S rRNA gene sequence types), which was highest for N. nova (14 secA1 sequence types), followed by Nocardia farcinica and N. veterana (n = 7 each); there was only a single sequence type among eight Nocardia paucivorans strains. The secA1 locus has potential for species identification as an adjunct to 16S rRNA gene sequencing but requires additional deduced amino acid sequence analysis. It may be a suitable marker for phylogenetic/subtyping studies. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Sun Z.,Beijing Tuberculosis and Thoracic Tumour Research Institute | Zhang J.,Beijing Tuberculosis and Thoracic Tumour Research Institute | Song H.,CAS Qingdao Institute of Bioenergy and Bioprocess Technology | Zhang X.,Beijing Tuberculosis and Thoracic Tumour Research Institute | And 5 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2010

OBJECTIVE: To determine the drug resistance spectrum and resistance levels of extensively drug-resistant (XDR-) and multidrug-resistant tuberculosis (MDR-TB) and TB resistant to either rifampicin (RMP, R) or isoniazid (INH, H; R/H-DR). DESIGN: Of 142 drug-resistant clinical isolates examined, 13 were XDR-TB, 66 were MDR-TB and 63 were R/H-DR. The drug resistance spectrum was tested by the absolute two-concentration method. Minimum inhibitory concentrations (MICs) were determined for the strains by agar dilution method on Löwenstein-Jensen slants. RESULTS: The drug resistance spectrum of XDR-TB, MDR-TB and R/H-DR TB isolates ranged from 4 to 9, 2 to 6 and 1 to 5 drugs, respectively. Over half of all XDRTB (53.8%), MDR-TB (66.7%) and R/H-DR (54.0%) isolates were resistant to two other anti-tuberculosis drugs; 38.5% of XDR-TB, 24.2% of MDR-TB and 28.6% of R/H-DR TB isolates were resistant to ≥3 additional anti-tuberculosis drugs in addition to those originally defined, demonstrating that the MIC values and the proportions of strains with higher MICs followed a trend of XDR-TB > MDR-TB > R/H-DR for INH, RMP, ofloxacin and ethambutol. CONCLUSION: XDR-TB, MDR-TB and R/H-DR TB isolates exhibited both increasingly broader resistance spectra and a higher percentage of strains with high MICs to more frequently resistant drugs, which might be related to patterns of TB chemotherapy. © 2010 The Union.


Guo Y.-L.,Beijing Tuberculosis and Thoracic Tumour Research Institute | Liu Y.,Beijing Tuberculosis and Thoracic Tumour Research Institute | Wang S.-M.,Beijing Research Institute for Tuberculosis Control | Li C.-Y.,Beijing Tuberculosis and Thoracic Tumour Research Institute | And 3 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2011

OBJECTIVE: To evaluate the distribution of the Mycobacterium tuberculosis Beijing genotype and the association of the genotype with drug-resistant M. tuberculosis strains in five provinces in China. DESIGN: M. tuberculosis strains (n = 158) isolated from five provinces of China were subjected to insertion sequence 6110 restriction fragment length polymorphism (RFLP), spoligotyping and mycobacterial interspersed repetitive units (MIRU) analyses. The prevalence of the Beijing genotype strains in each province was determined and compared. The proportion method was used to test the drug susceptibility of all strains. RESULT: Of the 158 strains, 123 (77.8%) were identified as the Beijing genotype by RFLP and spoligotyping. Nearly all the strains (n = 152, 96.2%) were grouped into 14 shared spoligotypes. Six other spoligotypes were unique to China. The prevalence of the Beijing genotype was significantly higher in the interior than in coastal areas (P < 0.001, OR 5.4, 95%CI 2.3-12.7). Resistance to rifampicin (RMP) was associated with the Beijing strain (P < 0.05, OR 3.7, 95%CI 1.2-11.1). CONCLUSION: The M. tuberculosis Beijing genotype varies in prevalence in different regions of China and is solely associated with RMP resistance. © 2011 The Union.

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