January 2014

How Can Common Organisms Cause Disease?

Organisms

The human body is a crowded place. In addition to the many human cells — which number approximately 37.2 trillion, according to a recent Annals of Human Biology paper — there are many, many more microbial cells that live in our bodies. Indeed, the NIH’s Human Microbiome Project notes “microbial cells are estimated to outnumber human cells ten to one,” including many that are commensal and live in perfect harmony with our own cells.

But sometimes these commensal microbes can cause disease, in particular when they leave their normal environment — such as the gut or pharynx — and spread to other sites. One Children’s Hospital researcher, Joseph W. St. Geme, III, MD, has spent much of his career working to better understand how this transition can happen. CHOP’s Physician-in-Chief and Chair of the Department of Pediatrics at the University of Pennsylvania, Dr. St. Geme has two NIH awards to support a pair of bacterial studies.

In addition to working as a clinician, Dr. St. Geme has worked for many years examining host-pathogen interactions, with a particular focus on the bacterium Haemophilus influenzae. Despite its somewhat misleading name, H. influenzae does not cause influenza, but is instead associated with invasive infections and localized respiratory tract disease. More recently, Dr. St. Geme has initiated studies of Kingella kingae, an emerging cause of bone and joint infections in young children.

Both H. influenzae and K. kingae are members of the normal bacterial flora, H. influenzae in the nasopharynx and K. kingae in the posterior pharynx. Dr. St. Geme said that “up to 70 percent or so of children in their first few years of life are colonized at some point with each of these organisms.”

The NIH awards, one from the National Institute of Allergy and Infectious Disease (NIAID) and the other from the National Institute on Deafness and Other Communication Disorders  (NIDCD), are supporting his investigations of K. kingae and H. influenzae, respectively. Dr. St. Geme has received ongoing support from the NIH to support his H. influenzae work since 1995 and has had the NIAID award to support his K. kingae work since September of 2013.

“In many ways the thrusts of the two projects, the general themes of the projects, are similar,” Dr. St. Geme said. Both projects are “investigations of host-pathogen interactions and focus on understanding how bacteria that are common, commensal organisms, usually not associated with disease, in some circumstances produce disease.”

Despite the fact that K. kingae is common in young children, the bacterium has only been appreciated as an important pathogen within the last fifteen years and is a leading cause of bone and joint infections in children younger than 3 or 4 years of age, Dr. St. Geme noted. Though K. kingae is a “fastidious organism” that has been historically difficult to grow in the lab, “improved cultivation techniques and molecular diagnostics have led to a surge of interest in this organism,” he said.

Last year Dr. St. Geme led a study that was published in Journal of Bacteriology and examined calcium binding in two K. kingae-associated adhesive proteins called PilC1 and PilC2. He also led a study that was published in PLoS One in September 2013 and elucidated K. kingae’s production of a polysaccharide capsule.

The NIAID award will allow Dr. St. Geme to build on his earlier K. kingae research, with investigations that he hopes will lead to “an improved understanding of the pathogenesis of disease … and will lay the foundation for developing a capsule-based vaccine.” In addition to Dr. St. Geme, CHOP researchers Katherine Rempe, Brad Kern, and Eric Porsch (who all moved to CHOP from Duke with Dr. St. Geme), as well as Duke’s Sue Grass, with whom Dr. St. Geme has been working since 1994, Jessica McCann, and Kim Starr have contributed to the H. influenzae and K. kingae projects.

“If we understand the bacterial determinants of the initial stages of infection, which are fundamental to the development of disease, we can use this information to develop new vaccines to prevent disease” Dr. St. Geme said. “Alternatively, we can use this information to develop novel antimicrobials that target bacterial factors required for infection.”

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