Infections caused by antibiotic-resistant bacteria remain a significant threat to human health worldwide. In the United States, about 2.8 million infections occur annually resulting in over 35,000 deaths. Globally, the impact is more severe with close to 1 million people, including 214,000 newborn babies, dying each year from such infections. Prevalent multidrug-resistant strains are the main contributors to these statistics. Such strains have led to the emergence of fast spreading ‘superbugs’ that are unresponsive to current treatment regimens. As a member of this category of pathogens, Methicillin-resistant Staphylococcus aureus (MRSA) is a highly infectious bacterial species that spreads easily among humans as a community-acquired infection. The threat posed by such pathogens is compounded by the decline in research aimed at developing new antibiotics. In fact, despite the alarming statistics of deaths resulting from such infections, only eight new antibiotics were approved for use by the FDA between 2010 and 2015. This slow discovery pace has led to dire projections of about 10 million fatalities resulting from resistant microbes by the year 2050. Therefore, there is an urgent need for the discovery and development of new therapies to tackle the emergence and spread of resistance, preventing an impending global catastrophe. The work in our laboratory seeks to identify novel therapeutics for use as antibiotics or antibiotic-adjuvants. Some of the on-going research in our laboratory is highlighted below. 

Bacteria use many strategies to evade antibiotic action. Enzymes are among the arsenal of weaponry bacteria frequently use to circumvent antibiotic action, thereby developing resistance. Our laboratory is interested in identifying and characterizing the activity of such enzymes, looking to elucidate the strategy they employ to cause resistance in pathogenic bacteria - with clinical implications.

Researchers use several approaches to fight bacterial pathogens. The development of new antibiotics is a strategy that has been used for decades since the discovery of the first antibiotic in 1928 by Sir Alexander Fleming. An alternative approach involves blocking the source of the observed resistance in bacterial cells. The activity of several enzymes is directly associated with resistance to many classes of antibiotics used in the clinic. These enzymes act in different ways to facilitate resistance, including target or drug modification. We are interested in understanding how such enzymes work and developing strategies to terminate their activity within bacterial cells, preventing the onset of resistance. We investigate three main groups of enzymes, including target- and antibiotic-modifying enzymes, and back-up enzymes whose activity mimics those performing critical cellular processes.

The continued spread of antibiotic resistance raises serious health concerns based on the eminent threat posed by bacterial pathogens. As a result, there is an urgent need to develop antibiotics with new modes of action that target essential pathways. We are interested in identifying novel molecular targets or pathways within bacterial cells that can be targeted to develop new antibiotic candidates.