Department of Microbiology and Immunology
Apoptosis and cell death; Immunology; Infectious Disease; Membrane Transport (Ion Transport); Microbial Pathogenesis; Molecular and Cellular Biology; Regulation of metabolism
My laboratory seeks to understand how the respiratory pathogen Streptococcus pneumoniae (pneumococcus), a gram-positive, extracellular bacterium, causes disease in humans and how human defense mechanisms, including breast milk, can better protect us from infection. Our team of undergraduate students, graduate students, a technician and a senior scientist work together and with several national and international collaborators to develop a better understanding in two areas.
First, we are interested in the protective effects of breast-feeding on bacterial infection. We have identified a protein-lipid complex in breast-milk, HAMLET (human alphalactalbumin made lethal to tumor cells) with strong bactericidal activity against S. pneumoniae and other respiratory tract pathogens. HAMLET‘s activity is especially important because it represents a new way to kill bacteria, even those resistant to antibiotics: it uses an essential pathway that the bacteria cannot become resistant against. Additionally, we have recently observed that HAMLET can sensitize antibiotic-resistant bacteria to the antibiotics they are resistant to, which may broaden the treatment arsenal against infectious diseases. Our current projects aim to understand the mechanism of HAMLET-induced bacterial death and sensitization of antibiotic-resistant bacteria, and the potential use of HAMLET or its targets in preventing and treating bacterial infections in vivo.
Second, we study how bacterial factors promote colonization and infection of the human host and how the host interact with this commensal during colonization and protects itself when pneumococci transition to infection. We have a major interest in understanding the bacterial and host interplay during pneumococcal colonization and infection. We have recently shown that pneumococci colonize the nasopharynx as a biofilm and have characterized the factors required for optimal colonization and biofilm formation and how these factors promote optimal genetic exchange by this naturally competent organism. We are also very interested in understanding the mechanisms responsible for transition from pneumococcal colonization to infection, with focus on host and bacterial interplay that modulate colonization of the nasopharynx. We are specifically interested in the role of virus infection and modulation of the nasopharyngeal microflora in this transition. We have shown that virus infection causes specific changes of the nasopharyngeal environment that result in release of highly virulent bacteria from the biofilms that disseminate into otherwise sterile sites to cause infection. A better understanding of these mechanisms and the transcriptional profiles of the bacterial populations involved in colonization and disease have the potential to provide novel antibiotic and vaccine targets.