The first case of pulmonary disease caused by Mycobacterium septicum in China

SummaryMycobacterium septicum is a rapidly growing Mycobacterium (RGM) that rarely causes pulmonary disease globally. We describe a case of M. septicum pulmonary disease, which to our knowledge is the first reported in China. The isolates were identified as M. septicum and were susceptible in vitro to amikacin, ciprofloxacin, ofloxacin, levofloxacin, kanamycin, and sulfamethoxazole

Genetic Diversity of Mycobacterium tuberculosis Isolates from Tibetans in Tibet, China

BACKGROUND: Tuberculosis (TB) is a serious health problem in Tibet where Tibetans are the major ethnic group. Although genotyping of Mycobacterium tuberculosis (M. tuberculosis) isolates is a valuable tool for TB control, our knowledge of population structure of M. tuberculosis circulating in Tibet is limited. METHODOLOGY/PRINCIPAL FINDINGS: In our study, a total of 576 M. tuberculosis isolates from Tibetans in Tibet, China, were analyzed via spoligotyping and 24-locus MIRU-VNTR. The Beijing genotype was the most prevalent family (90.63%, n = 522). Shared-type (ST) 1 was the most dominant genotype (88.89%, n = 512). We found that there was no association between the Beijing genotype and sex, age and treatment status. In this sample collection, 7 of the 24 MIRU-VNTR loci were highly or moderately discriminative according to their Hunter-Gaston discriminatory index. An informative set of 12 loci had similar discriminatory power with 24 loci set. CONCLUSIONS/SIGNIFICANCE: The population structure of M. tuberculosis isolates in Tibetans is homogeneous and dominated by Beijing genotype. The analysis of 24-locus MIRU-VNTR data might be useful to select appropriate VNTR loci for the genotyping of M. tuberculosis

Molecular typing of mycobacterium tuberculosis isolates circulating in Jiangsu Province, China

<p>Abstract</p> <p>Background</p> <p>Globally, China is the second place with high burden of tuberculosis (TB). To explore the characteristics of the pathogens of <it>Mycobacterium tuberculosis </it>(MTB) circulating in this area is helpful for understanding and controlling the spread of the strains. Recent developments in molecular biology have allowed prompt identification and tracking specific strains of MTB spreading through the population.</p> <p>Methods</p> <p>Spacer-oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive units variable number tandem repeat (MIRU-VNTR) were performed in combination to yield specific genetic profiles of 260 MTB strains isolated from 30 counties of Jiangsu province in China between June and July 2010. The spoligotyping results were in comparison to the world Spoligotyping Database of Institute Pasteur de Guadeloupe (SpolDB4). Drug susceptibility test (DST) was performed on all strains by proportion method on Lowenstein-Jensen (LJ) culture media.</p> <p>Results</p> <p>Based on the spoligotyping method, 246 strains displayed known patterns and 14 were absent in the database. Predominant spoligotypes belonged to the Beijing family (80.4%). By using the 24-loci VNTR typing scheme, 224 different patterns were identified, including 20 clusters and 204 unique patterns. The largest clade comprised 195 strains belonging to the Beijing family. The combination of spoligotyping and 24-loci MIRU-VNTR demonstrated maximal discriminatory power. Furthermore, we observed a significant association between Beijing family strains and drug-resistant phenotypes. The Beijing family strains presented increased risks for developing multi-drug resistant TB, with the OR (95% CI) of 11.07(1.45-84.50).</p> <p>Conclusions</p> <p>The present study demonstrated that Beijing family isolates were the most prevalent strains circulating in Jiangsu province of China. The utility of spoligotyping in combination with 24-loci MIRU-VNTR might be a useful tool for epidemiological analysis of MTB transmission.</p

Investigation on Mycobacterium tuberculosis Diversity in China and the Origin of the Beijing Clade

Contains fulltext : 124314.pdf (publisher's version ) (Open Access

Diversité génétique et résistance aux médicaments anti-tuberculeux de Mycobacterium tuberculosis en Chine

made possible by grant from European Community FP6 SSA grant "Tuberculosis China" N° 012166This thesis describes the geographical distribution of Mycobacterium tuberculosis genotypes in a major part of China and a study on the possible correlation with BCG vaccination and drug-resistance. The prevalence of drug resistance was investigated in 10 provinces, and drug resistance mutations in M. tuberculosis related to rifampicin and INH resistance were determined. The distribution of different genotypes of M. tuberculosis was investigated by using spoligotyping, large sequence polymorphism, and MLVA typing. The Beijing genotype represented 55 to 93% of the strains in the different provinces examined, with a gradient from South to North of China. Several other genotype families of M. tuberculosis were identified all belonging to the so-called "Modern" clade. Two of them, the China 2 and China 3 families, appear to be highly specific for China. Some members of the Central Asian family were found in one province whereas a possibly more ancestral strain was traced in another. The prevalence of drug resistance was determined among more than 2000 isolates from 10 provinces. Resistance against at least one drug was found in 45% of the isolates and MDR in about 29%. In China, no correlation was observed between the Beijing genotype and resistance/BCG vaccination, which is different from results in other countries. The distribution of the mutations in the rpoB gene of rifampicin resistant strains was determined. In addition, in INH resistant strains, the distribution of mutation in several genes was analysed. No mutation was detected in the oxyR and ahpC genes. This is the first time that such a large scale study is performed on the genetic diversity and drug resistance mechanisms of M. tuberculosis in China.Ce manuscrit décrit la distribution géographique des génotypes de Mycobacterium tuberculosis dans une large partie de la Chine, et l'étude d'une éventuelle corrélation avec la vaccination BCG et la résistance aux antibiotiques. La prévalence de la résistance a été analysée dans 10 provinces, et les mutations responsables de la résistance à la rifampicin et à l'INH ont été recherchées. La distribution des différents génotypes a été analysée par spoligotypage, par l'identification de délétions génomiques et par l'analyse du polymorphisme de répétitions en tandem (MLVA). Le génotype Beijing représente 55 à 93% des souches dans les provinces étudiées, avec un gradient allant du Sud vers le Nord de la Chine. Plusieurs autres familles sont identifiées, toutes appartenant à la clade dite " Moderne ". Les familles " Chine 2 " et " Chine 3 " qui représentent l'essentiel des autres souches sont rares en dehors de la Chine. Quelques souches de la famille CAS (Central Asia) sont également rencontrées dans une province et un ancêtre possible de la lignée Beijing dans une autre. La prévalence de la résistance aux antibiotiques a été mesurée parmi plus de 2000 isolats de 10 provinces. Le pourcentage de souches résistantes à au moins une drogue est de 45% et celui des souches multirésistantes est d'environ 29%. En Chine, à la différence d'autres pays, aucune corrélation n'est observée entre le génotype Beijing et la vaccination BCG. La distribution des mutations du gène rpoB a été déterminée ainsi que les mutations responsables de la résistance à l'INH. Aucune mutation n'est observée dans les gènes oxyR et ahpC. Cette étude est la première étude de grande envergure effectuée en Chine sur la diversité génétique de M. tuberculosis et sur les mécanismes de résistance aux antibiotiques

Study on genetic diversity and resistance to anti-TB drugs of mycobacterium tuberculosis in China

Ce manuscrit décrit la distibution géographique des génotypes de Mycobacterium tuberculosis dans une large partie de la Chine, et l étude d une éventuelle corrélation avec la vaccination BCG et la résistance aux antibiotiques. La prévalence de la résistance a été analysée dans 10 provinces, et les mutations responsables de la résistance à la rifampicin et à l INH ont été recherchées. La distribution des différents génotypes a été analysée par spoligotypage, identification de délétions génomiques et par MLVA. Le génotype Beijing représente 55 à 93% des souches dans les provinces étudiées, avec un gradient du Sud vers le Nord de la Chine. Plusieurs autres familles sont identifiées toutes appartenant à la clade dite Moderne . Les familles Chine 2 et Chine 3 semblent être spécifiques de la Chine. On identifie également quelques souches de la famille CAS (Central Asia) dans une province et un ancêtre possible de la lignée Beijing dans une autre. La prévalence de la résistance aux antibiotiques a été mesurée parmis plus de 2000 isolats de 10 provinces. Le pourcentage de souches résistantes à au moins une drogue est de 45% et celui des multirésistantes est environ 29%. En Chine on observe aucune corrélation entre le génotype Beijing et la vacination BCG ce qui n est pas le cas dans d autres pays. La distribution des mutations du gène rpoB a été déterminée ainsi que les mutations responsables de la résistance à l INH. Aucune mutation n est observée dans les gènes oxyR et ahpC.Cette étude est la première étude de grande envergure effectuée en Chine sur la diversité génétique de M. tuberculosis et sur les mécanismes de résistance aux antibiotiques.This thesis describes the geographical distribution of Mycobacterium tuberculosis genotypes in a major part of China and a study on the possible correlation with BCG vaccination and drug-resistance. The prevalence of drug resistance was investigated in 10 provinces, and drug resistance mutations in M. tuberculosis related to rifampicin and INH resistance were determined. The distribution of different genotypes of M. tuberculosis was investigated by using spoligotyping, large sequence polymorphism, and MLVA typing. The Beijing genotype represented 55 to 93% of the strains in the different provinces examined, with a gradient from South to North of China. Several other genotype families of M. tuberculosis were identified all belonging to the so-called Modern clade. Two of them, the China 2 and China 3 families, appear to be specific for China. Some members of the Central Asian family were found in one province whereas a possibly more ancestral strain was traced in another. The prevalence of drug resistance was determined among more than 2000 isolates from 10 provinces. Resistance against at least one drug was found in 45% of the isolates and MDR in about 29%. In China, no correlation was observed between the Beijing genotype and resistance/BCG vaccination, which is different from results in other countries.The distribution of the mutations in the rpoB gene of rifampicin resistant strains was determined. In addition, in INH resistant strains, the distribution of mutation in several genes was analysed. No mutation was detected in the oxyR and ahpC genes.This is the first time that such a large scale study is performed on the genetic diversity of M. tuberculosis in China.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Drug Susceptibility of 33 Reference Strains of Slowly Growing Mycobacteria to 19 Antimicrobial Agents

Objectives. Slowly growing mycobacteria (SGM) are prevalent worldwide and cause an extensive spectrum of diseases. Methods. In this study, the antimicrobial susceptibility of 33 reference strains of SGM to 19 antimicrobial agents was tested using a modified microdilution method. Results. Cefmetazole (32/33) and azithromycin (32/33) exhibited the highest antimicrobial activity, and dapsone (9/33) exhibited the lowest activity against the tested strains. Cefoxitin (30/33), cefoperazone (28/33), and cefepime (28/33) were effective against a high proportion of strains, and macrolides were also highly effective as well as offering the benefit of convenient oral administration to patients. Linezolid (27/33), meropenem (26/33), sulfamethoxazole (26/33), and tigecycline (25/33) showed the highest activity; clofazimine (20/33) and doxycycline (18/33) showed intermediate activity; and rifapentine (13/33), rifabutin (13/33), and minocycline (11/33) showed low antimicrobial activity, closely followed by thioacetazone (10/33) and pasiniazid (10/33), against the tested organisms. According to their susceptibility profiles, the slowly growing species Mycobacterium avium and Mycobacterium simiae were the least susceptible to the tested drugs, whereas Mycobacterium intracellulare, Mycobacterium asiaticum, Mycobacterium scrofulaceum, Mycobacterium szulgai, Mycobacterium branderi, and Mycobacterium holsaticum were the most susceptible. Conclusions. In summary, cephalosporins and macrolides, particularly cefmetazole, azithromycin, clarithromycin, and roxithromycin, showed good antimicrobial activity against the reference strains of SGM

Comparative Analysis of Human B Cell Epitopes Based on BCG Genomes

Background. Tuberculosis is a huge global health problem. BCG is the only vaccine used for about 100 years against TB, but the reasons for protection variability in populations remain unclear. To improve BCG efficacy and develop a strategy for new vaccines, the underlying genetic differences among BCG subtypes should be understood urgently. Methods and Findings. Human B cell epitope data were collected from the Immune Epitope Database. Epitope sequences were mapped with those of 15 genomes, including 13 BCGs, M. bovis AF2122/97, and M. tuberculosis H37Rv, to identify epitopes distribution. Among 398 experimentally verified B cell epitopes, 321 (80.7%) were conserved, while the remaining 77 (19.3%) were lost to varying degrees in BCGs. The variable protective efficacy of BCGs may result from the degree of B cell epitopes deficiency. Conclusions. Here we firstly analyzed the genetic characteristics of BCGs based on B cell epitopes and found that B cell epitopes distribution may contribute to vaccine efficacy. Restoration of important antigens or effective B cell epitopes in BCG could be a useful strategy for vaccine development

Polymorphism of 41 kD Flagellin Gene and Its Human B-Cell Epitope in Borrelia burgdorferi Strains of China

The 41 kD flagellin of Borrelia burgdorferi (B. burgdorferi) is a major component of periplasmic flagellar filament core and a good candidate for serodiagnosis in early stage of Lyme disease. Here, we chose 89 B. burgdorferi strains in China, amplified the gene encoding the 41 kD flagellin, and compared the sequences. The results showed that genetic diversity presented in the 41 kD flagellin genes of all 89 strains among the four genotypes of B. burgdorferi, especially in the genotype of B. garinii. Some specific mutation sites for each genotype of the 41 kD flagellin genes were found, which could be used for genotyping B. burgdorferi strains in China. Human B-cell epitope analysis showed that thirteen of 15 nonsynonymous mutations occurred in the epitope region of 41 kD flagellin and thirty of 42 B-cell epitopes were altered due to all 13 nonsynonymous mutations in the epitope region, which may affect the function of the antigen. Nonsynonymous mutations and changed human B-cell epitopes exist in 41 kD flagellin of B. burgdorferi sensu lato strains; these changes should be considered in serodiagnosis of Lyme disease