Senior Scholar Award in Global Infectious Disease
Roberto G. Kolter, Ph.D.
Harvard Medical School

Ecological Influences on Pathogen Genome Evolution

Most bacteria that exist on our planet do not cause diseases to humans. By and large these bacteria colonize diverse environments and carry out important processes in their habitats. Such processes are generally beneficial to humans. For example, only bacteria have the capacity to take the nitrogen that is abundant in the atmosphere, but which we cannot utilize as a nutrient, and converting it into a form that can be used by plants and animals. Some bacteria, however, are able to cause disease and their effects can, and have been, devastating. Examples of widespread effects of bacterial infections are the plagues that decimated Europe’s populations centuries ago and the ongoing pandemics of cholera that continue to wreak havoc in tropical countries today.

What makes these bacteria cause disease? We now know that disease-causing bacteria, in contrast to their harmless counterparts, contain specific genes that confer on them their virulence. But what we still do not understand very well at all is just how those genes come to be part of “genomes” (the entire collection of genes in any give organism) of these bacteria. Any environmental bacterium lacking virulence genes can conceivably acquire some of these. But what are the selective pressures that maintain the virulence genes present in the genome? Do they require that the organism come in contact with a human host and cause disease? Or, alternatively, are there environments outside of the host where microbes that contain virulence genes are more successful that those that lack them? Our proposed research aims at answering these questions. We will address them in two bacteria that can cause disease and which are widely disseminated on our planet. One is the marine bacterium that causes the disease cholera and is known as Vibrio cholerae. The second one is a ubiquitous soil microbe known as Pseudomonas aeruginosa. This bacterium does not normally cause disease but when humans are debilitated by injury or underlying illness its infections can be deadly. We will collect many samples of these microorganisms, both from clinical and environmental settings. Then we will analyze their entire genomes and determine differences and similarities among the different isolates of each. These analyses will guide our future experiments aimed at determining how the ecology of each isolate might have influenced the way each genome gained and/or lost virulence genes. Knowing the influences that particular environments have on the evolution of disease-causing bacteria could some day lead us to formulate predictive models on how changing environments can lead to the emergence or re-emergence of infectious diseases.

Contact Dr. Kolter.