Exploring and targeting potential druggable antimicrobial resistance targets ArgS, SecY, and MurA in Staphylococcus sciuri with TCM inhibitors through a subtractive genomics strategy.

Staphylococcus sciuri (also currently Mammaliicoccus sciuri) are anaerobic facultative and non-motile bacteria that cause significant human pathogenesis such as endocarditis, wound infections, peritonitis, UTI, and septic shock. Methicillin-resistant S. sciuri (MRSS) strains also infects animals that include healthy broilers, cattle, dogs, and pigs. The emergence of MRSS strains thereby poses a serious health threat and thrives the scientific community towards novel treatment options. Herein, we investigated the druggable genome of S. sciuri by employing subtractive genomics that resulted in seven genes/proteins where only three of them were predicted as final targets. Further mining the literature showed that the ArgS (WP_058610923), SecY (WP_058611897), and MurA (WP_058612677) are involved in the multi-drug resistance phenomenon. After constructing and verifying the 3D protein homology models, a screening process was carried out using a library of Traditional Chinese Medicine compounds (consisting of 36,043 compounds). The molecular docking and simulation studies revealed the physicochemical stability parameters of the docked TCM inhibitors in the druggable cavities of each protein target by identifying their druggability potential and maximum hydrogen bonding interactions. The simulated receptor-ligand complexes showed the conformational changes and stability index of the secondary structure elements. The root mean square deviation (RMSD) graph showed fluctuations due to structural changes in the helix-coil-helix and beta-turn-beta changes at specific points where the pattern of the RMSD and root mean square fluctuation (RMSF) (< 1.0 Å) support any major domain shifts within the structural framework of the protein-ligand complex and placement of ligand was well complemented within the binding site. The ß-factor values demonstrated instability at few points while the radius of gyration for structural compactness as a time function for the 100-ns simulation of protein-ligand complexes showed favorable average values and denoted the stability of all complexes. It is assumed that such findings might facilitate researchers to robustly discover and develop effective therapeutics against S. sciuri alongside other enteric infections.

SARS-CoV-2: big seroprevalence data from Pakistan-is herd immunity at hand?

PURPOSE: Seroprevalence surveys from different countries have reported SARS CoV-2 antibodies below 20% even in the most adversely affected areas and herd immunity cannot be predicted till more than half of the population gets the disease. The purpose of this survey was to estimate the magnitude of community-based spread of the infection, associated immunity, and the future prospects and proximity to a 'herd community'. METHODS: The study was undertaken as a cluster randomized, cross-sectional countrywide survey. This largest community-based seroprevalence data of SARS-CoV-2 were collected between 15th and 31st July, 2020 from seven randomly selected cities belonging to the three most populous provinces of Pakistan. The FDA approved kit of ROCHE was used for detection of SARS-CoV-2 antibodies. RESULTS: Serum samples of 15,390 participants were tested for SARS CoV-2 antibodies with an overall seroprevalence of 42.4%. The seroprevalence ranged from 31.1% to 48.1% in different cities with the highest in Punjab province (44.5%). In univariable analysis, the odds of seropositivity was higher in men compared to women (OR: 1.10, 95% CI: 1.01-1.19, P < 0.05). In multivariable analysis, the risk of being seropositive was lower (OR 0.72, 95% CI: 0.60-0.87, P < 0.01) in younger group (≤ 20 years) than in those aged above 60 years. CONCLUSION: The study concluded that despite a reasonable seroprevalence, the country is yet to reach the base minimum of estimations for herd immunity. The durability of immunity though debated at the moment, has shown an evidenced informed shift towards longer side.

Pleomorphic Adenoma of Minor Salivary Gland.

Pleomorphic adenoma is a benign tumor of salivary glands, arising from minor salivary glands, is very rare and presents with a minor female predilection; and the highest occurrence is between the fourth and sixth decades of life. It is of glandular origin, usually presenting as a slowly growing, painless, firm swelling that does not cause ulceration of the overlying mucosa. In this case, a 27-year male presented with swelling on buccal mucosa for three years. The swelling was firm and well circumscribed. Excisional biopsy was done under general anesthesia and the mass was excised. The histopathological evaluation revealed pleomorphic adenoma. This case highlights the need to keep this entity in the differential diagnosis of intra-oral indolent swellings of some duration. Key Words: Pleomorphic adenoma, Buccal mucosa, Minor salivary glands.