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1.
Artigo em Inglês | MEDLINE | ID: mdl-31398482

RESUMO

Mycobacterium tuberculosis Beijing genotype strains are widespread globally. However, there has been no systematic study on the association between Beijing genotype and the characteristics of drug resistance. In this study, 359 M. tuberculosis isolates from south China were collected and their background information, genotype diversity and drug resistance was investigated. The results revealed that 66.0% of strains (237/359) were categorised as Beijing genotype. There was no statistical difference between Beijing and non-Beijing genotype strains in terms of patient sex, age, place of residence and treatment history. Drug resistance testing showed that 34.8% (125/359) of isolates were resistant to at least one of the seven drugs tested. The proportions of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis were 17.0% and 1.4%, respectively. Previously treated patients presented a significantly higher risk of developing drug resistance than new cases. Although the prevalence of drug resistance was higher in Beijing genotype than in non-Beijing genotype strains, there was no significant difference between these two genotypes in the multivariate analysis. Even in re-treated patients, the association of Beijing genotype with drug resistance was not significant. This study provides an insight into genotype diversity and demonstrates the characteristics of drug resistance in Beijing genotype strains, which will be useful in generating efficient tuberculosis prevention and control strategies in China.

2.
Biomed Environ Sci ; 32(6): 427-437, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262388

RESUMO

OBJECTIVE: This study aimed to characterize the diagnostic and vaccine potential of a novel Mycobacterium tuberculosis antigen Rv0674. METHODS: To evaluate the diagnostic potential and antigenicity of Rv0674, IgG was evaluated using ELISA and interferon (IFN)-γ was done by using ELISpot assay among TB patients and healthy donors. For immunogenicity evaluation, BALB/c mice were immunized with Rv0674. Cytokine production was determined by cytokine release assay using an ELISA kit, and the antibodies were tested using ELISA. RESULTS: The results of serum Elisa tests showed that Rv0674 specific immunoglobulin G (IgG) response was higher in TB patients than negative controls. And Rv0674 had good performance in serological test with sensitivity and specificity of 77.1% and 81.1%, respectively. While it shows poor sensitivity and specificity of 26.23% and 79.69% for IFN-γ tests. In BALB/c mice, Rv0674 adjuvant by DDA/Poly I:C could also induce a high level of IFN-γ, interleukin-2 and interleukin-6 as well as a high IgG titer in both high- and low-dose groups indicating that Rv0674 is essential in humoral and cellular immunity. Moreover, the cytokine profile and IgG isotype characterized Rv0674 as a Th1/Th2-mixed-type protective immunity with the predominance of Th1 cytokines. CONCLUSION: Rv0674 may be a good potential candidate for the development of TB serological diagnosis and a new TB vaccine.


Assuntos
Antígenos de Bactérias/imunologia , Tuberculose/imunologia , Adulto , Idoso , Animais , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Tuberculose/diagnóstico , Adulto Jovem
3.
Biomed Environ Sci ; 31(4): 290-299, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29773092

RESUMO

OBJECTIVE: Macrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria (NTM) isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China. METHODS: Four macrolides, including clarithromycin (CLAR), azithromycin (AZM), roxithromycin (ROX), and erythromycin (ERY), were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23S rRNA and erm, were analyzed with nucleotide sequence analysis. RESULTS: Varied effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191A and T2221C on rrl were specific for the M. abscessus complex (MABC). Seven sites, G2140A, G2210C, C2217G, T2238C, T2322C, T2404C, and A2406G, were specifically carried by M. avium and M. intracellulare. Three sites, A2192G, T2358G, and A2636G, were observed only in M. fortuitum and one site G2152A was specific for M. gordonae. The genes erm(39) and erm(41) were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar. CONCLUSION: The susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23S rRNA and erm, failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Macrolídeos/farmacologia , Mycobacterium/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , China , Regulação Bacteriana da Expressão Gênica , Humanos , Mycobacterium/genética , Polimorfismo Genético
4.
Artigo em Inglês | MEDLINE | ID: mdl-29084750

RESUMO

The EmbCAB proteins have been considered a target for ethambutol (EMB). Mutations in embCAB are known to confer most EMB resistance. However, the knowledge about the effects of embCAB mutations on the EMB resistance level and about the role of mutation-mutation interactions is limited in China. Here, we sequenced embCAB among 125 Mycobacterium tuberculosis isolates from China and quantified their EMB MICs by testing growth at 10 concentrations. Furthermore, a multivariate regression model was established to assess the effects of both individual mutations and multiple mutations. Our results revealed that in China, 82.6% of EMB-resistant isolates (71/86 isolates) harbored at least one mutation within embCAB Most of the mutations were located in the embB and embA upstream region. Several individual mutations and multiple mutations within this region contributed to the different levels of EMB resistance. Their effects were statistically significant. Additionally, there was an association between high-level EMB resistance and multiple mutations.

5.
Tuberculosis (Edinb) ; 107: 1-4, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29050755

RESUMO

Rapid detection of resistance to the second-line drugs is essential for early initiation of appropriate anti-tubercular treatment regimen among multi-drug tuberculosis (MDR-TB). In this study, we applied a multiplex allele-specific PCR (MAS-PCR) to identify the mutations on codons 90 and 94 of gyrA and nucleotide 1401 of rrs for detecting ofloxacin (OFX) and kanamycin (KAN) resistance in 139 MDR-TB isolates from China. Using the traditional phenotypic method as the reference, MAS-PCR detected resistance to OFX and KAN with sensitivities of 67.3% and 76.5%, respectively, and specificities of 100.0%. Therefore, MAS-PCR assays can be used for rapid detection of second-line drug resistance among MDR-TB in China, enabling early administration of appropriate treatment regimens to the affected MDR-TB patients.


Assuntos
Técnicas Bacteriológicas , Análise Mutacional de DNA/métodos , Farmacorresistência Bacteriana Múltipla/genética , Reação em Cadeia da Polimerase Multiplex , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Antituberculosos/uso terapêutico , China , DNA Girase/genética , Genótipo , Humanos , Canamicina/uso terapêutico , Resistência a Canamicina/genética , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Ofloxacino/uso terapêutico , Valor Preditivo dos Testes , Proteínas Ribossômicas/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
6.
Tuberculosis (Edinb) ; 97: 33-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26980493

RESUMO

Genotyping results and DNA sequencing analysis of 235 Mycobacterium tuberculosis (M. tuberculosis) isolates from China indicated that mutations at codon 995 (Pro CCG to Pro CCA) and 701 (Ile ATT to Thr ACT) in lysX gene (Rv1640c), are specific markers for Beijing and modern Beijing strains, respectively. This observation was also confirmed by 24 genomes of M. tuberculosis strains from other countries. Moreover, a simple and fast multiplex allele-specific PCR (MAS-PCR) method for detecting mutations at codon 995 and 701 in lysX has been established and used to screen 235 DNA samples obtained from M. tuberculosis isolates. In all cases, Beijing and modern Beijing strains were identified correctly.


Assuntos
Proteínas de Bactérias/genética , Técnicas Bacteriológicas , Análise Mutacional de DNA , Lisina-tRNA Ligase/genética , Reação em Cadeia da Polimerase Multiplex , Mutação , Mycobacterium tuberculosis/genética , Tuberculose/diagnóstico , Proteínas de Bactérias/química , China , Códon , Marcadores Genéticos , Genótipo , Humanos , Mycobacterium tuberculosis/patogenicidade , Fenótipo , Valor Preditivo dos Testes , Conformação Proteica , Estabilidade Proteica , Reprodutibilidade dos Testes , Tuberculose/microbiologia
7.
Diagn Microbiol Infect Dis ; 83(2): 150-3, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26254141

RESUMO

We investigated the spectrum and frequency of mutations in rpsL, rrs, and gidB among 140 multidrug-resistant tuberculosis (MDR-TB) clinical isolates from China. The association between mutations and different genotypes was also analyzed. Our data revealed that 65.7% of MDR-TB were resistant to streptomycin (STR), and 90.2% of STR-resistant isolates were Beijing strains. STR resistance was correlated with Beijing family (P=0.00). Compared with phenotypic data, detection of mutations for the combination of these 3 genes exhibited 94.6% sensitivity, 91.7% specificity, and 93.6% accuracy. The most common mutations in STR-resistant isolates were rpsL128, 262, and rrs514, of which rpsL128 showed association with Beijing lineage (P=0.00). A combination of these 3 mutations can serve as the reliable predictors for STR resistance, showing the sensitivity, specificity, and accuracy of 85.9%, 97.9%, and 90.0%, respectively. Furthermore, gidBA276C, not A615G, was Beijing lineage specific. These findings are useful to develop rapid molecular diagnostic methods for STR resistance in China.


Assuntos
Antibacterianos/farmacologia , Genótipo , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Estreptomicina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/isolamento & purificação , Adulto Jovem
8.
Antimicrob Agents Chemother ; 59(4): 2045-50, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25605360

RESUMO

Ethambutol (EMB) plays a pivotal role in the chemotherapy of drug-resistant tuberculosis (TB), including multidrug-resistant tuberculosis (MDR-TB). Resistance to EMB is considered to be caused by mutations in the embCAB operon (embC, embA, and embB). In this study, we analyzed the embCAB mutations among 139 MDR-TB isolates from China and found a possible association between embCAB operon mutation and EMB resistance. Our data indicate that 56.8% of MDR-TB isolates are resistant to EMB, and 82.2% of EMB-resistant isolates belong to the Beijing family. Overall, 110 (79.1%) MDR-TB isolates had at least one mutation in the embCAB operon. The majority of mutations were present in the embB gene and the embA upstream region, which also displayed significant correlations with EMB resistance. The most common mutations occurred at codon 306 in embB (embB306), followed by embB406, embA(-16), and embB497. Mutations at embB306 were associated with EMB resistance. DNA sequencing of embB306-497 was the best strategy for detecting EMB resistance, with 89.9% sensitivity, 58.3% specificity, and 76.3% accuracy. Additionally, embB306 had limited value as a candidate predictor for EMB resistance among MDR-TB infections in China.


Assuntos
Antituberculosos/farmacologia , Proteínas de Bactérias/genética , Etambutol/farmacologia , Proteínas de Membrana/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Pentosiltransferases/genética , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose/microbiologia , China , DNA Bacteriano/genética , Humanos , Testes de Sensibilidade Microbiana
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