Terri N. Ellis

 Research in my lab focuses on the outer surface of pathogenic (disease causing) Gram-negative bacteria. Gram-negative bacteria, unlike other cells, are surrounded by a distinctive cell wall and second, outer phospholipid membrane. Bacterial species within this group include such well known bacteria as E. coli, Salmonella, and Vibrio cholerae. This second membrane contains molecules distinctive to this group of bacteria that contribute to the virulence of pathogenic strains of these bacteria in addition to roles in basic physiology. From this outer membrane, bacteria can secrete outer membrane vesicles. These vesicles can contribute to bacterial pathogenesis by altering host cell functions and triggering inflammation. Beyond this cell wall, many Gram-negative bacteria also secrete a capsule, a thick, slimy polysaccharide layer that encases the entire bacteria. The capsule is a known virulence factor of disease causing bacteria, as it limits the ability of phagocytic white blood cells to grip, engulf, and destroy the bacteria as part of the body’s immune defenses.

 I am interested in understanding how modifications to these outer surfaces, including the outer membrane, secreted outer membrane vesicles, and capsule, all contribute to the virulence of disease causing bacteria. For this work, I have focused on Klebsiella pneumoniae. This bacterial species is the third most common cause of nosocomial (hospital acquired) infections and is responsible for over 7,000 deaths per year in the United States. Klebsiella is known to cause urinary tract infections, pneumonia, liver abscesses, and bacterial sepsis. Alarmingly, up to 50% of these infections are resistant to most current antibiotics.
 

Antibiotic resistance in bacteria is primarily a result of acquisition of well characterized resistance genes. However, resistance in Klebsiella commonly pairs acquisition of these resistance genes with other changes to the outer surface components as well. Some of these changes include: increased production of the outer polysaccharide capsule, halted synthesis of specific transport proteins (porins) embedded in the outer membrane that allow antibiotics to penetrate into the cell, and chemical modifications to the lipid components of the outer membrane. All of these changes have been observed in clinical isolates of resistant strains from lethal infections. My research focuses on how these changes to the outer surface, that are associated with antibiotic resistance, impact the virulence of the bacteria and the progression of disease. While these changes have been well documented in the clinic, and can be used as diagnostic markers of resistance, their impact on bacterial pathogenesis have not been fully investigated.

 My lab utilizes a range of proteomic, biochemical, cell biology, genetic, and immunology based techniques. Using this integrative approach, we investigate how small changes to the outer surface of these bacteria trigger larger downstream alterations in virulence. Incorporated into all investigations is student training. I rely upon both undergraduate and graduate students in all aspects of my research, as evidenced by their inclusion as first and co-authors on all publications, and presentations, in both oral and poster format, at regional and national level scientific conferences.