ABSTRACT
Neisseria gonorrhea is a sexually transmitted disease from gonorrhea that lacks treatment; despite the urgency, the absence of adequate drugs, lack of human correlates of protection, and inadequate animal models of infection have delayed progress toward the prevention of gonococcal infection. Lactobacillus crispatus is a lactic acid bacterium typically found in the human vaginal microbiota. Peptides from L. crispatus have shown a potential therapeutic option for targetting N. gonorrhea. Bioinformatics analysis is important for speeding up drug target acquisition, screening refinement, and evaluating adverse effects and drug resistance prediction. Therefore, this study identified an antimicrobial peptide from the bacteriocin immunity protein (BIP) of L. crispatus using the bioinformatics tool and Collection of Antimicrobial Peptide (CAMPR3). Based on the AMP score and highest ADMET properties, the peptide SM20 was chosen for docking analysis. SM20 was docked against multiple proteins from the genome of the AMR bacterium N. gonorrhea using an online tool; protein-peptide interactions were established and visualized using the PyMol visualizing tool. Molecular docking was carried out using the CABSdock tool, and multiple conformations were obtained against the membrane proteins of N. gonorrhoea. The peptide SM20 exhibited higher docking scores and ADMET properties. Therefore, SM20 could be further encapsulated with cellulose; it can be applied topically to the genital tract to target N. gonorrhea infection. The controlled release of the antimicrobial peptide from the gel can provide sustained delivery of the treatment, increasing its efficacy and reducing the risk of resistance development.
ABSTRACT
Ultraviolet B wavelength ray radiation (UVB) is an environmental stressor with detrimental effects to the aquatic and human systems but also enhances adverse effects when combined with several other environmental factors such as temperature and pollution. UV rays induce cellular oxidative damage and impair motility. This study aimed to examine the photo-protective activity of flavonoid luteolin against UV-B irradiation-induced oxidative stress and cellular damage using zebrafish. An in-vivo photoaging model was established using UV-B irradiation in zebrafish larvae exposed to 100 mJ/cm2. Data demonstrated that UV-B irradiation of swimming water enhanced production of ROS and superoxide anions as well as depleted total glutathione levels in zebrafish larvae. UV-B irradiation also triggered cellular damage and membrane rupture in zebra fish. Further, 100 mJ/cm2 of UV-B radiation exposure to adult-wild type zebrafish co-exposed with intraperitoneally (ip) injected luteolin upregulated the local neuroendocrine axes by activating vascular endothelial growth factor (VEGF) and elevating levels of pro-inflammatory cytokines IL-1ß and TNF-α. Histologically, UV-B irradiation induced skin lesions and locomotory defects with clumping and degeneration of brain glial cells. However, luteolin effectively inhibited the excess production of reactive oxygen species (ROS) and decreased superoxide anion levels induced by UV-B irradiation. Luteolin restored the depleted glutathione levels. In addition, luteolin blocked apoptosis and lipidperoxidation. Luteolin protected adult zebrafish by downregulating the pro-inflammatory cytokine protein expression levels and diminishing VEGF activation. Luteolin also alleviated locomotory defects by inhibiting activation of microglia and inflammatory responses by preventing accumulation of glial cells and vacuolation. Data demonstrate that luteolin may protect zebrafish from UV-B-induced photodamage through DNA-protective, antioxidant and anti-inflammatory responses.
