Protein turnover via the Pup-proteasome system (PPS) is essential for nitric oxide resistance and virulence of Mycobacterium tuberculosis, the causative agent of tuberculosis. Our study revealed components of PPS as novel determinants of intrinsic antifolate resistance in both M. tuberculosis and non-pathogenic M. smegmatis. Lack of expression of the prokaryotic ubiquitin-like protein (Pup) or the ligase, PafA, responsible for ligating Pup to its protein targets, enhanced antifolate susceptibility in M. smegmatis. Cross-species expression of M. tuberculosis homologs restored wild type resistance to M. smegmatis proteasomal mutants. Targeted deletion of prcA and prcB encoding the structural components of PPS proteolytic core similarly resulted in reduced antifolate resistance. Furthermore, sulfonamides were synergistic with acidified nitrite, and the synergy against mycobacteria was enhanced in the absence of proteasomal activity. In M. tuberculosis, targeted mutagenesis followed by genetic complementation of mpa, encoding the regulatory subunit responsible for translocating pupylated proteins to the proteolytic core, demonstrated a similar function of PPS in antifolate resistance. Overexpression of dihydrofolate reductase, responsible for the reduction of dihydrofolate to tetrahydrofolate, or disruption of Lonely Guy gene, responsible for PPS controlled production of cytokinins, abolished PPS-mediated antifolate sensitivity. Together, our results show that PPS protects mycobacteria from antimicrobial antifolates via regulating both folate reduction and cytokinin production.
Introduction: Acne is a chronic inflammatory disorder of the pilosebaceous unit with differential pathogenesis. To elucidate the roles of hormones in acne pathogenesis, we conducted a study to evaluate the serum testosterone, estradiol, progesterone levels in women with acne vulgaris. Methods: We conducted a cross-sectional descriptive study, and 175 women with acne vulgaris were examined; their serum estradiol, progesterone, testosterone were analyzed by chemiluminescence technique and compared with the healthy control group. Results: Increased serum hormone levels in women with acne vulgaris were accounted for 29.7%, and hyperandrogenism was accounted for 16.0% of cases. We found significant differences in testosterone levels (mean value, 55.67±25.56 versus 38.37±10.16 ng/dL, p<0.05) respectively in the acne group and the control group. However, the estradiol level of the acne group (323.15±93.31 pmol/L) was lower than the control group (370.94±58.88 pmol/L) with p<0.05). No statistically significant differences were found for progesterone (0.60±0.38 versus 0.50±0.15 ng/mL, p>0.05) levels. Moreover, we did not find the relationship between serum hormone levels and the severity of acne vulgaris. Conclusion: This study showed that the female acne vulgaris patients may have high serum testosterone levels and low serum estradiol levels compared with those of female controls. However, hormone alterations had no correlation with the acne grades.
This study was designed to identify the genetic basis that results in the development of antibiotic resistance in Campylobacter spp. We carried out a molecular examination of 75 strains looking for resistance factors. These strains were isolated from faecal samples of pigs, chickens and ducks at Dong Thap province. There were 89.3 % strains which showed mutations on DNA gyrase-gyrA gene at the position 86 (C257T and T227G). There were also a further 32 % strains that showed mutations on gene cmeR encoding the efflux CmeABC pump system. This study has also shown that 29.3 % of Campylobacter spp. have mutations in fluoroquinolone (FQ) resistance on both genes gyrA and cmeR. In comparison with Campylobacter jejuni with the mutation C257T (Thr-86-Ile), Campylobacter coli has another mutation at T227G (Thr-86-Met). This mutation, encoding FQ resistance, is common in both swine and poultry but has not yet been identified in Viet Nam. As well as FQ resistance, resistance to erythromycine (Ery) has been detected in C. coli, in 10 strains erythromycin resistance, with a mutation at position A2075G. There was 1 strain which carried two mutations A2075G and A2074C at 23S-rRNA gene, and 2 mutant strains with a double mutation at A2075G and A2076C. In summary, there were three strains of C. coli with double mutations encoding Ery resistance at Dong Thap and this resistance characteristic has not been identified eslewhere.
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