Targeting Molecular Mechanism of Obesity and Multidrug Resistance in Bacteria by Natural Products

A rapid decline in research and development on new antibiotics coincides with increasing frequency of infections caused by multi-drug-resistant pathogens. The key reason of bacterial resistance is the indiscriminate or suboptimal use of antibiotics. The outbreak of methicillin-resistant Staphylococcus aureus (MRSA), which occurred over fifty years ago, is now widespread throughout the world. S. aureus is the most common bacterial pathogen, which causes skin, soft-tissue, and endovascular infections, pneumonia, septic arthritis, endocarditis, osteomyelitis, and sepsis. As the efficacy of currently available antibiotics is declining due to MDR, there is an urgent need to develop new approaches to meet this challenge.

In the present study, we discovered several novel and potent inhibitors of MDR S. aureus (EMRSA-17, EMRSA-16, MRSA-252 and Pak clinical isolates) from natural and synthetic sources. Resistance-reversal studies at the molecular level were carried out by employing flow cytometric and microscopic techniques. Synergistic and partial synergistic effects of these compounds along with antibiotics were investigated. This work has so far resulted in the identification of novel “helper molecules”, which can increase the efficacy of existing antibiotics to over 1000 fold.

Obesity is also an emerging challenge to human well-being. The molecular cascade involved in obesity and associated disorders is not fully understood. Proliferation of adipocytes plays in important role in the on-set and progression of obesity. Understanding the phenomena of adipogenesis is of major importance as adipocyte dysfunction makes an important contribution to metabolic diseases due to obesity. Differentiation of preadipocytes to adipocytes not only results in increasing number of adipocytes but also provide a large pool of fat depots in adipose tissues. Thus one strategy to treat obesity is to reduce the adipocyte numbers and fat content through targeting the mature adipocytes by diverse molecular activities. Among different therapeutic interventions, the discovery of effective antiadipogenic compounds from various sources is considered to be a promising approach. Our recent research is focused on the study of the inhibitory effects of natural and synthetic compounds such as steroids, flavonoids, terpenes alkaloids and sulfonamides, on the proliferation of adipocytes, in a dose dependent manner, as well as to check their effects on to the mature adipocytes. This study has resulted in the identification of several new inhibitors of the adipogenesis process