My laboratory is interested in understanding the bacterial factors that promote successful colonization by the diverse population of pneumococci. This organism spends majority of its life in the polymicrobial environment of the nasopharynx where it is exposed to attack by the host immune system as well as by other inhabiting or invading organisms. Although the interaction of the bacteria with the host immune system in controlling or modifying colonization has been the focus of intense study by others, the role of inter-bacterial interactions that impact successful colonization in a polymicrobial environment are less well understood. We have recently identified a heterogeneous locus in pneumococcus encoding antimicrobial peptides called pneumocins. These peptides target unrelated pneumococci as well as other members of the respiratory flora and presumably give producing strains an advantage during colonization. We have shown that these peptides are produced during murine colonization, allowing producing strains to out-compete sensitive competitors. We are currently examining several aspects of pneumocin production based on these observations:

1/ Pneumocin production is highly regulated in pneumococcus. We have shown that pneumocin activity is controlled by at the transcriptional and post transcriptional level by 2 two component systems and an outer surface protease. We are currently examining the environmental factors that influence this complex regulatory network and working to identify upstream regulators. In addition, we are investigating the regulatory mechanism underlying transcriptionally silent strains, the phenotype found in the majority of clinical isolates.
2/ We are currently studying a panel of isolates from a densely colonized population in South Africa that consists of pneumococci derived from duel and singly colonized individuals. By characterizing the pneumocin locus from this strain collection, we hope to better understand the importance of the pneumocin locus in promoting successful colonization and enabling co-colonization.
3/ This strain collection has already allowed us to identify novel broadly active loci that inhibit the growth of a majority of pneumococci tested. Further work on these loci involves characterizing and purifying the active peptides for testing in animal models of colonization and disease. We will also use this information to better understand the components of pneumocin immunity.