University of Hyderabad, India
Title: New face of an old drug: Celecoxib as an antibacterial agent
Dr. Arunasree M K, Ph. D. (University of Hyderabad) Assistant Professor Department of Animal Sciences School of Life Sciences University of Hyderabad, India. Research Interests Histone deacetylases and protein-protein interactions. Histone Deacetylases (HDAC) enzymes catalyze the cleavage of acetyl functions from histone and nonhistone proteins. HDAC enzymes are evolutionarily conserved from insects to humans, indicating their important role. So far, 18 mammalian deacetylase enzymes have been identified and divided into three classes based on their structural homologies to the three distinct yeast HDACs: Rpd3 (class I), Hda1 (class II) and Sir2/Hst (class III). Histone deacetylation leads to condensed chromatin (heterochromatin) and therefore no longer accessible to transcriptional machinery.This type of gene silencing can be mediated by recruiting HDACs to different promoter regions as they cannot interact directly with DNA or associated histone proteins. Because of this, HDACs are always part of protein complexes binding to specific regions of DNA. The components of these multiprotein complexes also differ cell-type specifically and are poorly characterized. Therefore we are trying to characterize few of these protein complexes. Also crystal structures of HDACs (except for HDAC8) are not available due to the posttranslational modifications (PTMs) of these proteins. We are also interested in identifying and characterizing the PTMs of HDACs.
Staphylococcus aureus, one of the opportunistic gram positive bacteria, is known for multidrug resistance to antibiotics. The frequency of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA) infections are increasing globally. MRSA is one of the two common bacterial pathogens that cause mastitis in cows and buffaloes leading to great loss to Indian economy. Misuse and overuse of antibiotics for the treatment of microbial infections has increased the emergence of pan-antibiotic resistant organisms, superbugs. Discovery of new antibiotics is both time and money dependent. Drug repositioning or drug repurposing is encouraged by Food and Drug Administration (FDA) and has gained importance in last few years. With this background, we have demonstrated that cyclooxygenase-2 (COX-2) specific inhibitor, celecoxib, is not only an anti-inflammatory drug but also has the property of antibacterial activity when used in combination with antibiotics on laboratory strains of S aureus (Kalle and Rizvi, 2010). We are evaluating efficacy of this therapy on MRSA strains isolated from humans and bubaline mastitis samples. The preliminary results are convincing and indicate that celecoxib could be used in combination with antibiotics to treat multidrug resistance in bacteria.