Drug Resistance; Otitis Media; Pneumonia; Respiratory Tract Infections; Pulmonary Disease, Chronic Obstructive
CPIRT - Pulmonary Infection Research and Treatment
Professor Pettigrew's research focuses on infectious diseases of
the respiratory tract. Her current work utilizes a combined
approach involving molecular biology and infectious disease epidemiology to
identify bacterial virulence factors important for otitis media caused by the
gram-positive pathogen Streptococcus
pneumoniae. In collaboration with researchers in the Center for Perinatal,
Pediatric and Environmental Epidemiology, Professor Pettigrew is also studying interactions
between viruses and bacterial pathogens as they impact on upper respiratory
tract infections in children and the pathogenesis of chronic obstructive pulmonary disease in adults.
Extensive Research Description
Dr. Pettigrew’s research is driven by a desire to understand processes that tip the balance between asymptomatic colonization and disease. Because the risks of colonization and disease are associated with host characteristics, the biological agent, and the environment, her research requires an understanding of several different disciplines including epidemiology, microbiology, and statistics. One major project utilizes a molecular epidemiologic approach to identify tissue specific virulence factors of the gram-positive pathogen Streptococcus pneumoniae. S. pneumoniae colonizes the nasopharynx of up to 55% of healthy young children. Asymptomatic carriage is far more common than disease, yet these bacteria are important causes of otitis media, pneumonia, sepsis, and meningitis. Conjugate vaccine formulations are available for children, but these do not cover all 92 pneumococcal serotypes. Given these concerns, and increasing rates of antibiotic resistance among pneumococcal isolates, it is important to gain a better understanding of the virulence characteristics of S. pneumoniae that influence their propensity to cause disease. It is also important that we understand the distribution of these virulence determinants among strains in circulation at the population level. This will facilitate the development of novel strategies to prevent pneumococcal disease.
Additional research projects focuses on the epidemiology of polymicrobial interactions between S. pneumoniae and other bacteria that colonize the same niche in the upper respiratory tract. Colonization by S. pneumoniae is a critical early step in the disease process. Several hundred different bacterial species colonize the upper respiratory tract of a single individual. Our research indicates that competitive interactions between bacteria in the nasopharynx differ by the number and type of bacteria species present. These data have implications for the development of probiotics and for antibiotic and vaccination strategies that target carriage of colonizing bacterial species. Such strategies may alter the nasopharyngeal flora, which may in turn have unintended consequences for disease incidence. We are expanding our research to examine interactions between bacteria and respiratory tract viruses (e.g. respiratory syncytial virus and adenovirus) and by taking advantage of recent advances in sequencing technology. Our newest projects utilize next generation sequencing methods to characterize the microbial ecology of bacteria colonizing the upper respiratory tract of infants and young children. These data will also lead to increased understanding of the human microbiome and how competitive interactions between bacteria and viruses lead to disease.
- Expression of IgA proteases by Haemophilus influenzae in the respiratory tract of adults with chronic obstructive pulmonary disease Murphy, T.M., Kirkham, C., Jones, M.M., Sethi, S., Kong, Y., and Pettigrew, M.M. Journal of Infectious Diseases. 2015; 212:1798-1805.
- Innovating in health care management education: Development of an accelerated MBA/MPH degree program at Yale Pettigrew, M.M., Forman, H.P., Pistell, A.F., and Nembhard, I.M. American Journal of Public Health. 2015; 105:S68-S72.
- Changes in the pneumococcal transcriptome during transition from biofilm formation to invasive disease upon influenza A virus infection. Infection and Immunity. Pettigrew, M.M., Marks, L.R., Kong, Y., Gent, J. F. and Hakansson. Infection and Immunity. A.P. 2014; 82:4607-19.
- Antibacterial resistance leadership group: Open for business. Chambers, H. F., Bartlett, J. G., Bonomo, R. A., Cosgrove, S., Cross, H., Daum, R.S., Evans, S.R., Kreiswirth, B.N., Lautenbach, E., Patel, R., Pettigrew, M.M., Rodvoid, K., Spelling, B., and Fowler, V.G. Clinical Infectious Diseases. 2014; 58:1571-6.
- Upper respiratory tract microbial communities, acute otitis media pathogens and antibiotic use in healthy and sick children. Pettigrew, M.M., Laufer, A.S., Gent, J.F., Fennie, K.P., Kong, Y. and Metlay, J.P. Applied and Environmental Microbiology. 2012; 78:6262-70.
- Microbial communities of the upper respiratory tract and otitis media. Laufer, A.S., Metlay, J.P., Gent, J.F., Fennie, K.P., Kong, Y. and Pettigrew, M.M. mBio. 2011; 2: e00245-10.