High-level persistence of biofilm formation in in methicillin resistant Staphylococcus aureus

Aims@#Biofilm formation by Methicillin-resistant Staphylococcus aureus on a variety of surfaces and detection of the biofilm-forming population by the most reliable method is very much essential to diagnose the nosocomial infection caused by S. aureus. @*Methodology and results@#This study is aimed to evaluate the biofilm producing ability of S. aureus by qualitative Congo red agar (CRA), and quantitative microtitre plate (MTP) methods. The morphological difference of biofilms analysis was done by SEM (Scanning Electron Microscope) and genotyping analysis of mecA and femA for determination of MRSA among isolated S. aureus strains and to check the biofilm producers among MRSA strains. Biofilm production was found to be at different intensities by MTP. The strong, moderate and weak biofilm producers were found to be 38.63%, 31.81%, and 29.54% respectively. The strong adherent biofilm formed by representative isolate developed a dense biofilm with thick mucus three-dimensional multilayered structure of macroscopic dimension. Conversely, SEM analysis of moderate and weak biofilm representative strain failed to form a monolayer of scattered single cells to three-dimensional structure. The 47.72% of S. aureus isolates have shown positive for the genotypic analysis of mecA and femA. The strong and moderate biofilm forming MRSA was found to be 38.63% and 9.09%, respectively. @*Conclusion, significance and impact of study@#The great challenge is associated with biofilm mediated infection caused S. aureus healthy and hospitalized individual hence the present study reinforces the need of precautionary measures to avoid the indiscriminate use of antibiotics in case of biofilm-forming MRSA.

Identification of New Inhibitors for Human SIRT1: An in-silico Approach.

BACKGROUND: Human SIRT1 is a class III histone deacetylase (HDAC) family protein. As the overexpression of hSIRT1 leads to cancer, inhibiting its HDAC function may be a better strategy for the treatment of cancer. Till now, only a few reported inhibitor compounds have reached the stage of animal studies; hence, identifying high efficacy inhibitors of hSIRT1 is essential. OBJECTIVE: The main objective of the study is to obtain a new class of inhibitor compounds of hSIRT1 by the rational structure-based method. METHODOLOGY: We performed virtual screening using AutoDock Vina for the HDAC domain of hSIRT1 against the Drug- Bank library containing 1,716 compounds. The recently determined crystal structure of the HDAC domain of hSIRT1 (PDB Id: 4KXQ) was used for docking studies. Subsequently, we performed molecular dynamics simulations and an invitro deacetylase assay for selected compounds. RESULTS: Virtual screening studies yielded seven compounds from two chemical classes, namely diphenyl and oxycoumarin derivatives. Molecular dynamic simulations confirmed that the predicted seven compounds bind well to their respective complex structures. Moreover, four commercially available drugs containing the predicted compounds showed significant inhibition of hSIRT1 deacetylase activity in comparison to the known hSIRT1 inhibitor (sirtinol). CONCLUSION: Our results indicate that the compounds of the diphenyl and oxycoumarin series may serve as useful scaffolds in the development of new chemical libraries of hSIRT1 inhibitory activity.

A compendium of molecules involved in vector-pathogen interactions pertaining to malaria.

Malaria is a vector-borne disease causing extensive morbidity, debility and mortality. Development of resistance to drugs among parasites and to conventional insecticides among vector-mosquitoes necessitates innovative measures to combat this disease. Identification of molecules involved in the maintenance of complex developmental cycles of the parasites within the vector and the host can provide attractive targets to intervene in the disease transmission. In the last decade, several efforts have been made in identifying such molecules involved in mosquito-parasite interactions and, subsequently, validating their role in the development of parasites within the vector. In this study, a list of mosquito proteins, which facilitate or inhibit the development of malaria parasites in the midgut, haemolymph and salivary glands of mosquitoes, is compiled. A total of 94 molecules have been reported and validated for their role in the development of malaria parasites inside the vector. This compendium of molecules will serve as a centralized resource to biomedical researchers investigating vector-pathogen interactions and malaria transmission.