Sixty-three rifampicin-resistant (Rif r ) isolates of Mycobacterium tuberculosis from Kaohsiung, Taiwan, were analysed for mutations in the core region (69 bp, codons 511-533) of the rpoB gene. Some 84·1 % (53/63) of the resistant isolates showed mutations in this region, especially in codons 531 (41·5 %), 526 (18·9 %), 516 (15·1 %) and 533 (7·5 %). Five novel alleles of a total of 16 different types of mutations were identified in Rif r isolates. Ten Rif r isolates (15·9 %) exhibited no mutations in the core region of rpoB. Also, they did not show mutations in another 365 bp fragment (codons 99-220) of rpoB. The agar proportion method was used to determine the relationship between the degree of rifampicin resistance and alterations in the core region of rpoB. The results revealed that the mean MIC was 92·38 ìg ml À1 for the 53 isolates with a mutation in the core region, whereas the mean MIC of the other 10 isolates without mutations was only 24·8 ìg ml À1 . This indicates that the isolates with mutations in the core region had higher levels of resistance than those without mutations in this region. IS6110 restriction fragment length polymorphism (RFLP) was used for typing of 55 Rif r M. tuberculosis isolates. Isolates contained two to 19 copies of IS6110, with sizes ranging from 600 to 16 000 bp. The majority (85 %) contained six to 16 copies. No strains lacking IS6110 were found. A total of 54 of 55 RFLP types were defined at the 90 % similarity level. The observation of varied IS6110-associated banding patterns indicates that an outbreak of drugresistant tuberculosis did not occur in this area. INTRODUCTIONAmong infectious diseases, tuberculosis (TB) is one of the most frequent causes of death in the world, with more than 2 million TB-related deaths reported each year (Dye et al., 1999). In 1997, an estimated 8 million new cases were reported and approximately 2 billion people, one third of the world's population, were infected with Mycobacterium tuberculosis (Dye et al., 1999). TB is one of the most important communicable diseases in Taiwan. It was the twelfth most common cause of death in 1998. The rates of incidence and mortality of TB per 100 000 population were respectively 64·89 and 6·93 in the same year (Kan, 2000). In recent years, the control of TB has been impeded by the emergence of drug-resistant M. tuberculosis strains (Kan, 2000).Rifampicin has proven to be an effective antituberculosis agent and its use has greatly shortened the duration of chemotherapy for the treatment of TB. Rifampicin resistance heralds higher rates of treatment failure and death for the patient and a poor outcome if the isolate is also resistant to isoniazid (Goble et al., 1993). The action of rifampicin is believed to interfere with transcription in bacteria by binding to the â subunit of RNA polymerase (the product of the rpoB gene) (Jin & Gross, 1988). Mutations in certain highly conserved codons encoded by rpoB account for 'single step' high-level resistance to rifampicin in M. tuberculosis (Telenti et al., 1993). Mor...
Rheumatoid arthritis (RA) and periodontitis are suggested to be closely linked based on microbial dysbiosis, but limited subgingival bacteria have been proven in the pathogenesis of RA. We enrolled 30 RA patients and 25 controls and divided them into three groups with matched age, gender, and diabetes statuses: group AM (all of the matched participants), group PD (periodontally diseased), and group PH (periodontally healthy). Their subgingival microbial composition was determined by V3–V4 16S rRNA gene sequencing. Significant differences in subgingival microbial clustering between the RA patients and controls were observed in groups AM and PD. Among the taxa enriched in RA, Aminipila butyrica and Peptococcus simiae were the only two species displaying positive correlation to the level of anti-citrullinated protein antibodies (ACPAs) in both of the groups. Surprisingly, the median of relative abundances of A. butyrica and P. simiae were 0% in the controls of group PD. Furthermore, a gene encoding arginine deiminase with the capability to produce citrulline was addressed in the complete genome sequence of A. butyrica. This is the first study to elucidate the important roles of A. butyrica and P. simiae as periodontal bacteria leading to RA possibly through the induction of ACPA production.
Aim: The activation of NLRP3 inflammasome leads to the stimulation of cytokines and is significantly involved in the pathogenesis and progression of autoimmune diseases. The purpose of this study is to examine the associations of NLRP3 gene polymorphisms with rheumatoid arthritis (RA) and primary Sjogren’s syndrome (SS) patients. Methods: A total of 239 patients with RA, 285 patients with primary SS, and 170 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells, and gene polymorphisms were genotyped through the TaqMan assay. Antinuclear antibody (ANA), anti-Ro, and anti-CCP antibodies were detected using immunofluorescence immunoassay. Results: The T allele of rs4612666 CT elevated the susceptibility to RA disease. The RF titer during diagnosis of RA was significantly high in RA patients with the A allele of rs12079994 G/A polymorphism. The titer of anti-CCP during diagnosis of RA was high in the absence of the C allele of rs10754558 C/G polymorphisms in RA patients. Antinuclear antibody and anti-CCP were positively associated with the A allele of rs12079994 G/A polymorphism in primary SS. The C allele of rs4612666 C/T was negatively associated with ANA in primary SS. Conclusions: The results have shown that NLRP3 gene polymorphisms may play a role in the pathogenesis of RA and primary SS.
The bactericidal activity of monocytes in patients with ReA is lower than that in healthy controls. The SLC11A1 274C/T and 823C/T polymorphisms may be associated with the decreased bactericidal activity of the monocytes.
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