Tremellomycetes, a fungal class in the subphylum Agaricomycotina, contain well-known opportunistic and emerging human pathogens. The azole drug fluconazole, used in the treatment of diseases caused by some species of Tremellomycetes, inhibits cytochrome P450 monooxygenase CYP51, an enzyme that converts lanosterol into an essential component of the fungal cell membrane ergosterol. Studies indicate that mutations and over-expression of CYP51 in species of Tremellomycetes are one of the reasons for fluconazole resistance. Moreover, the novel drug, VT-1129, that is in the pipeline is reported to exert its effect by binding and inhibiting CYP51. Despite the importance of CYPs, the CYP repertoire in species of Tremellomycetes has not been reported to date. This study intends to address this research gap. Comprehensive genome-wide CYP analysis revealed the presence of 203 CYPs (excluding 16 pseudo-CYPs) in 23 species of Tremellomycetes that can be grouped into 38 CYP families and 72 CYP subfamilies. Twenty-three CYP families are new and three CYP families (CYP5139, CYP51 and CYP61) were conserved across 23 species of Tremellomycetes. Pathogenic cryptococcal species have 50% fewer CYP genes than non-pathogenic species. The results of this study will serve as reference for future annotation and characterization of CYPs in species of Tremellomycetes.

Cytochrome P450 monooxygenase CYP51 (sterol 14α-demethylase) is a well-known target of the azole drug fluconazole for treating cryptococcosis, a life-threatening fungal infection in immune-compromised patients in poor countries. Studies indicate that mutations in CYP51 confer fluconazole resistance on cryptococcal species. Despite the importance of CYP51 in these species, few studies on the structural analysis of CYP51 and its interactions with different azole drugs have been reported. We therefore performed in silico structural analysis of 11 CYP51s from cryptococcal species and other Tremellomycetes. Interactions of 11 CYP51s with nine ligands (three substrates and six azoles) performed by Rosetta docking using 10,000 combinations for each of the CYP51-ligand complex (11 CYP51s × 9 ligands = 99 complexes) and hierarchical agglomerative clustering were used for selecting the complexes. A web application for visualization of CYP51s’ interactions with ligands was developed (http://bioshell.pl/azoledocking/). The study results indicated that Tremellomycetes CYP51s have a high preference for itraconazole, corroborating the in vitro effectiveness of itraconazole compared to fluconazole. Amino acids interacting with different ligands were found to be conserved across CYP51s, indicating that the procedure employed in this study is accurate and can be automated for studying P450-ligand interactions to cater for the growing number of P450s.

Antiretroviral therapy (ART) has significantly improved outcomes in individuals with human immunodeficiency virus (HIV), yet its long-term cardiovascular effects, especially on hypertension risk, remain debated. This pilot study investigated hypertension risk factors in HIV-positive patients undergoing ART and aimed at hypothesis generation rather than drawing definitive causal conclusions. Seventy HIV-infected adults without baseline hypertension were enrolled and followed. Hypertension was defined using the 2017 ACC/AHA guidelines by the South African Hypertension Society. Data on demographic, anthropometric, metabolic, inflammatory, coagulation, and HIV-related variables were collected. Cox regression analysis identified independent predictors of hypertension. Participants had a median age of 37 years (IOR = 10.96), with 84.3% being female. After a median ART exposure of 61.01 months (range: 2–164), 27 individuals (38.6%) developed high blood pressure. In multivariable Cox models adjusting for metabolic syndrome and BMI, age ≥ 35 years was associated with a 2.2-fold higher hypertension risk (Hazard Ratio [HR]: 2.2; 95% Confidence Interval [CI]: 1.04–4.55; p = 0.04). Elevated triglycerides significantly increased risk, with a 7.9-fold higher likelihood of hypertension (HR: 7.9; 95% CI: 1.04–59.5; p = 0.046). ART regimen type, whether initial or current, did not independently predict hypertension. In conclusion, hypertension is prevalent during ART. We hypothesized that traditional cardiovascular risk factors, notably age ≥35 years and hypertriglyceridemia, were key independent predictors, emphasizing the need for routine cardiovascular risk assessment in HIV management.

Bacillus safensis strain WOIS2, a nitrile-metabolizing bacterium, was isolated from solid waste leachates at the Olusosun dumpsite, Ojota, Lagos State, Nigeria. Here, we present the draft genome sequence of strain WOIS2. These data provide valuable information on the bioprospecting of B. safensis nitrilase and other intriguing genes of interest.

Background/Objectives: Adolescent girls and young women (AGYW) have a high burden of sexually transmitted infections (STIs). This study examined the prevalence of Chlamydia trachomatis, its association with human papillomavirus (HPV), and other associated factors among AGYW of rural communities. Methods: Secondary data on C. trachomatis, HPV, and linked questionnaires from 214 sexually active AGYW were used. Self-collected vaginal specimens were previously tested using the Allplex™ STI Essential Assay and Roche Linear Array HPV genotyping assay. Results: The overall prevalence of C. trachomatis was 29.4% (63/214), and it was not influenced by age. The majority of the AGYW were C. trachomatis negative and HPV positive (52.4%, 111/212), followed by being C. trachomatis and HPV co-infected (23.6%, 50/212), C. trachomatis and HPV co-negative (18.4%, 39/212) and least were C. trachomatis positive and HPV negative (5.7%, 12/212). There was an increased prevalence of being HPV infected among C. trachomatis individuals than being C. trachomatis positive among HPV positive individuals (RR: 2.60, 95% CI: 2.00–3.38, p < 0.0001). C. trachomatis positive AGYW had a significantly higher association of HPV types targeted by Cervarix^® HPV vaccine (HPV-16 and/or -18) than C. trachomatis negatives (RR: 2.58, 95% CI: 1.37–4.82, p = 0.005), targeted by Gardasil^®4 HPV vaccine (HPV-6, -11, -16 and/or -18; RR: 2.21, 95% CI: 1.32–3.65, p = 0.005) and Gardasil^®9 HPV vaccine (HPV-6, -11, -16, -18, -31, -33, -45, -52 and/or -58; RR: 1.92, 95% CI: 1.37–2.67, p < 0.001). Conclusions: There was a high burden of C. trachomatis and HPV coinfection. C. trachomatis coinfection influenced HPV genotype prevalence and distribution, including those that are targeted by the current commercial HPV vaccines, suggesting that the high burden of C. trachomatis among AGYW may pose challenges to the ongoing HPV vaccination program. Integrated STI screening and prevention strategies are needed in rural South African settings.