Bacteria are the most abundant organisms on earth. They are found almost every possible biological niche, from ordinary soil to deep oceans and geological formations. They also interact with the human body; some bacteria are essential for life while others can be deadly. The ability of bacteria to flourish in such a wide range of environments is due in large part to the enzymes that populate their cell membranes. These enzymes make up the active interface between the cell and the environment. One of their roles is to ensure the interior of the cell is a hospitable place for the biochemistry of life in spite of changing and often hostile conditions outside. Among the most important of these membrane enzymes are the ones that transport ions into and out of the cell. These ion transporters are essential for maintaining favorable concentrations of ions inside the cell, but ion transport is also at the heart of energy production in the cell. Transport of H+ and Na+ create gradients that provide energy for processes as diverse as motility of the cell, import of nutrients and extrusion of chemicals that are toxic to the cell--the latter is responsible for a significant class of antibiotic resistance. 

The focus of my research is the physiology and biochemistry that allow bacteria to adapt and proliferate in diverse environments. In particular, we are interested in understanding the role of ion gradients involved in producing energy and maintaining stable, favorable internal conditions in spite of changing environments.

We work on 3 interrelated projects: 1) Energy metabolism of the gut bacterium Bacteroides fragilis, where we are investigating a new paradigm in which this organism, previously classified as a strict anaerobe, actually depends on aerobic respiration for its survival and role in the community of intestinal microflora. 2) Adaptation to changing environments by the opportunistic pathogen Pseudomonas aeruginosa, focusing on enzymes that generate and consume the Na+ and H+ gradients and how these systems function and interoperate. 3) Functional and mechanistic studies of two redox-driven Na+ pumping enzymes: NQR and RNF from Vibrio cholerae and other bacteria. 

The projects in my laboratory range from basic microbiology, characterizing the physiology of bacteria and their interactions with other cells, to biophysical chemistry, spectroscopy (visible, fluorescence, FTIR, and EPR) and rapid kinetics in order to understand the molecular mechanisms of ion transport and energy production enzymes. We study Vibrio cholerae, the cause of the disease cholera, Pseudomonas aeruginosa which are implicated in cystic fibrosis, as well as Bacteroides fragilis, which are beneficial gut bacteria, and use infection models including mice, macrophages, and fruit flies. 

We are particularly interested in two enzymes: Na+-pumping NADH:quinone oxidoreductase (NQR), a respiratory enzyme found only in bacteria that uniquely pumps Na+ instead of H+, and Na+ pumping Ferredoxin:NAD oxidoreductase (RNF). These enzymes, are found in many pathogens, marine bacteria, and colon bacteria and are important for adaptation and proliferation of these organisms in diverse environments. In the case of NQR, my group defined the redox cofactors of the enzyme, their redox reactions, the pathway of electron transfer through these cofactors, and which of these electron transfer steps are linked to energy conservation. We are currently trying to understand the pathway that carries Na+ across the membrane and the mechanism that couples the redox reactions to this uphill transport of Na+.