ABSTRACT
The virulence factor Type IV pili (T4P) are surface appendages used by the opportunistic pathogen Pseudomonas aeruginosa for twitching motility and adhesion in the environment and during infection. Additionally, the use of these appendages by P. aeruginosa for biofilm formation increases its virulence and drug resistance. Therefore, attenuation of the activity of T4P would be desirable to control P. aeruginosa infections. Here, a computational approach has been pursued to screen natural products that can be used for this purpose. PilB, the elongation ATPase of the T4P machinery in P. aeruginosa, has been selected as the target subunit and virtual screening of FDA-approved drugs has been conducted. Screening identified two natural compounds, ergoloid and irinotecan, as potential candidates for inhibiting this T4P-associated ATPase in P. aeruginosa. These candidate compounds underwent further rigorous evaluation through molecular dynamics (MD) simulations and then through in vitro twitching motility and biofilm inhibition assays. Notably, ergoloid emerged as a particularly promising candidate for weakening the T4P activity by inhibiting the elongation ATPases associated with T4P. This repurposing study paves the way for the timely discovery of antivirulence drugs as an alternative to classical antibiotic treatments to help combat infections caused by P. aeruginosa and related pathogens.Communicated by Ramaswamy H. Sarma.
ABSTRACT
OBJECTIVE: To evaluate the prevalence of pathogens, Chlamydia trachomatis, Neisseria gonorrhea and Trichomonas vaginalis, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, and Ureaplasma parvum in women via multiplex-polymerase chain reaction (PCR)-deoxyribonucleic acid (DNA). MATERIALS AND METHODS: Cervical swabs of 273 women in reproductive age who underwent gynecologic examination in our outpatient clinic were evaluated using the multiplex-PCR-DNA method. The presence of cervicitis, contraceptive methods, marital status, and the number of partners were evaluated. RESULTS: One hundred six (39%) of the 273 women had at least one bacterium, 25 women (9.8%) had two bacteria, and three women (1%) had three bacteria. U. urealyticum was the most frequently encountered bacterium (13.9%), followed by M. hominis (12.8%), U. parvum (12.4%), C. trachomatis (5.4%), M. genitalium (2.9%), N. gonorrhea (2.5%), and T. vaginalis (0.3%). Bacterial infection was detected more frequently in women aged <25 years, single, who had multiple partners, and clinically diagnosed with cervicitis. The cervicitis rate was 39% in our study. M. genitalium was significantly more frequent in women with cervicitis than in women without cervicitis (5.6 vs. 1.2%, p=0.005). C. trachomatis and N. gonorrhea, which are often associated with cervicitis, were comparable in women with and without cervicitis. CONCLUSION: Women with clinically diagnosed cervicitis or even with a normal-appearing cervix should be tested using multiplex-real-time PCR-nucleic-acidamplification tests on suspicion of such an infection. M. genitalium is an emerging bacterial agent for cervicitis along with C. trachomatis and N. gonorrhea.
ABSTRACT
UNLABELLED: Hormone replacement therapy (HRT) is widely used with a large variety of regimens and medications. For each of these regimens the goal is the same but there is always a fear about side effects, especially on breast. Mammographic screening is a standard tool for all women receiving hormone replacement therapy. Breast density is very important, because it interferes with the sensitivity of the evaluation and it is also a predictor of malignity. OBJECTIVE: We planned a study to investigate the effects of tibolone on mammographic breast density. DESIGN AND METHODS: We studied 70 postmenopausal women who started tibolone therapy (2.5 mg per day) after initial mammography and blood samples taken for biochemical examinations. None of the women used any hormone replacement therapy before. Eleven of them either discontinued the therapy or lost contact. After 1 year, we evaluated 59 women by mammographic status, using Wolfe classification. Mammographies were analyzed by two independent radiologists. RESULTS: Mammographies of 59 women were compared with the initial ones. While in the low density patterns, there was a slight increase (15%; P < 0.05); in the higher density groups, there was a decrease of 25% as observed by one radiologist, and 16% according to the other (P < 0.05). None of the women had a diffuse, high density pattern. There was no statistically significant inter-observer variation between two radiologists (P < 0.05). CONCLUSIONS: Wolfe classification allows easy interpretation of mammographic evaluation and the results are reproducible. Tibolone, as a tissue-specific steroid, does not have an estrogenic effect on breast cells. We found that it might limit, even reverse breast density increase, especially in postmenopausal women with high breast density.
