Enterobacter aerogenes and Klebsiella pneumoniae are the leading cause of severe hospital-acquired infections across the globe, particularly... Show moreEnterobacter aerogenes and Klebsiella pneumoniae are the leading cause of severe hospital-acquired infections across the globe, particularly in the US and Europe. These bacteria contribute heavily to the alarming threat of emergence of multiple drug resistant strains, enabling them to survive a wide spectrum of antibiotics. One of the key factors involved in drug resistance is the production of biofilms, a complex exopolysaccharide matrix that acts as a protective component and increase their resistance to external factors including antibiotics. In this study, we described that targeting the bacterial respiratory metabolism entirely disrupts pathways used for energy synthesis and substantially inhibits bacterial growth. Moreover, the metabolic inhibitors decreased the production of biofilms by these bacteria. Two key factors being the bacterial growth and biofilm development were analyzed in this research study. The data indicates that HQNO has the highest inhibition effect which targets essential enzyme complex Na+-NQR in bacterial growth as well as biofilm formation. Thus, the structure of HQNO can potentially be suited for new antibiotic development to combat the problem of multidrug resistant bacteria. M.S. in Biology, May 2017 Show less
V. cholerae is a gastrointestinal pathogen which causes extreme watery diarrhea and results in over 120,000 deaths per year worldwide. It is... Show moreV. cholerae is a gastrointestinal pathogen which causes extreme watery diarrhea and results in over 120,000 deaths per year worldwide. It is especially prevalent in developing countries that lack proper water treatment and in areas struck by natural disasters such as hurricanes. P. aeruginosa is an opportunistic pathogen that is ubiquitous in nature, and increasingly found in hospitals burn wards, sinks, catheters and other surgical equipment. Both bacteria are developing increased antibiotic resistance through several mechanisms, with one of the most common ones being the formation of a complex exopolysaccharide matrix known as a biofilm. In this study, using metabolic inhibition, we determined that Na+-NQR is essential for the growth of V. cholerae and P. aeruginosa in both nutrient rich and physiological conditions. We were also able to confirm that inhibition of this enzyme, in both growth conditions, resulted in decreased biofilm production, subsequently eliminating one of the main mechanisms for antibiotic resistance of these bacteria. M.S. in Biology, May 2017 Show less
