Antibacterial Effect of Ethanolic Extracts of Dodonaea viscosa L. Jacq. and Mammea americana L. against Staphylococci Isolated from Skin Lesions.

Background: The resistance to antibiotics shown by some dermatological pathogenic microorganisms has increased the interest of pharmaceutical and cosmetic industries in developing natural products that possess different biological activities, including antimicrobial effects. Methods: In the present investigation, the antibacterial activity of ethanolic extracts of Dodonaea viscosa aerial part and Mammea americana leaves and seed was evaluated against resistant strains of Staphylococcus isolated from skin lesions and against S. aureus ATCC 25923 (reference strain). Column chromatography (CC) and preparative thin-layer chromatography (PTLC) were used to obtain separate fractions of the seed extract of M. americana. We also determined the antimicrobial resistance of the strains against antibiotics using the agar disc diffusion assay. In addition, phytochemical screening was performed by colorimetric standard techniques. Results: M. americana seed extract showed the highest antibacterial activity with MBC from 2.3 µg/mL to 19.5 µg/mL without differences with gentamicin (p = 0.998). The isolated strain S. epidermidis I showed the highest antimicrobial resistance against the tested antibiotics. PTLC-fractions of M. americana seed extract showed MBC from 3.2 µg/mL to 40.7 µg/mL against S. epidermidis I and S. aureus 25923 (reference), respectively, which suggests a synergistic effect of the secondary metabolites present in the crude ethanolic extract compared to its active PTLC-fractions, where only coumarins and compounds with lactone groups were detected in the phytochemical screening. Conclusion: M. americana seed extract has promising effects that should be considered in further studies as an alternative or adjuvant in treating skin infections caused by staphylococci.

In vivo and in vitro human gene essentiality estimations capture contrasting functional constraints.

Gene essentiality estimation is a popular empirical approach to link genotypes to phenotypes. In humans, essentiality is estimated based on loss-of-function (LoF) mutation intolerance, either from population exome sequencing (in vivo) data or CRISPR-based in vitro perturbation experiments. Both approaches identify genes presumed to have detrimental consequences on the organism upon mutation. Are these genes constrained by having key cellular/organismal roles? Do in vivo and in vitro estimations equally recover these constraints? Insights into these questions have important implications in generalizing observations from cell models and interpreting disease risk genes. To empirically address these questions, we integrate genome-scale datasets and compare structural, functional and evolutionary features of essential genes versus genes with extremely high mutational tolerance. We found that essentiality estimates do recover functional constraints. However, the organismal or cellular context of estimation leads to functionally contrasting properties underlying the constraint. Our results suggest that depletion of LoF mutations in human populations effectively captures organismal-level functional constraints not experimentally accessible through CRISPR-based screens. Finally, we identify a set of genes (OrgEssential), which are mutationally intolerant in vivo but highly tolerant in vitro. These genes drive observed functional constraint differences and have an unexpected preference for nervous system expression.