Anders P. Hakansson, Ph.D., Assistant Professor Department of Microbiology & Immunology
145 Biomedical Research Building
Phone: (716) 829-6058
Fax: (716) 829-2158
Alternate web-site: http://www.hakanssonlab.com/
My laboratory is focused on investigating the pathogenesis of the gram-positive, extracellular pathogen Streptococcus pneumoniae (pneumococcus). S. pneumoniae is one of the leading causes of morbidity and mortality from respiratory tract and invasive infections in children and the elderly worldwide. Pneumococci effectively colonize the human nasopharynx and cause infections such as pneumonia, acute otitis media (AOM), meningitis and sepsis by disseminating to otherwise sterile sites. My laboratory has two main focuses:
1. We are interested in better understanding how the pneumococcus interact with host cells in the respiratory tract during colonization and transition to infection. Our studies are focused on bacterial factors and strategies that promote colonization and infection of the human host (adherence, invasion, biofilm formation etc) but also on the strategies used by the host to protect itself from bacterial challenge (mucosal innate and adaptive immunity; see figure). One of the factors we study is the pneumococcal enzyme dihydrolipoamide dehydrogenase (DLDH) that is required for the bacteria to cause infection in mouse infection models. Preliminary evidence indicates that DLDH directly binds to and regulates the transport of solutes through several ABC transport systems in the bacterial membrane.
2. One host factor of particular interest to us is human milk. Breast-feeding is well documented to protect against a variety of infections, including a strong protection against respiratory tract infections. During my graduate studies I discovered a protein complex from human milk, HAMLET, that induced apoptosis in tumor cells without affecting healthy cells. Besides killing tumor cells, HAMLET effectively kills pneumococci as well as other respiratory tract pathogens. Our current projects are aimed at understanding the mechanism of HAMLET-induced bacterial death and the potential use of HAMLET in preventing and treating established pneumococcal infections. Understanding these mechanisms may also help us define how HAMLET kills tumor cells.
1. Hakansson A, Zhivotovsky B, Orrenius S, Sabharwal H, and Svanborg C (1995). Apoptosis induced by a human milk protein. Proc Natl Acad Sci U S A 92: 8064-8068.
2. Hakansson A, Svensson M, Mossberg AK, Sabharwal H, Linse S, Lazou I, Lönnerdal B, and Svanborg C (2000). A folding variant of alpha-lactalbumin with bactericidal activity against Streptococcus pneumoniae. Mol Microbiol 35: 589-600.
3. Hakansson A, Roche H, Mirza S, McDaniel LS, Brooks-Walter A, and Briles DE (2001). Characterization of binding of human lactoferrin to pneumococcal surface protein A. Infect Immun 69: 3372-3381.
4. Smith AW, Roche H, Trombe MC, Briles DE, and Hakansson A (2002). Characterization of the dihydrolipoamide dehydrogenase from Streptococcus pneumoniae and its role in pneumococcal infection. Mol Microbiol 44: 431-448.
5. Hakansson A, Cywes Bentley C, Shakhnovic EA, and Wessels MR (2005). Cytolysin-dependent evasion of lysosomal killing. Proc Natl Acad Sci U S A 102: 5192-5197.
6. Hakansson AP, and Smith AW (2007). Enzymatic Characterization of Dihydrolipoamide Dehydrogenase from Streptococcus pneumoniae Harboring Its Own Substrate. J Biol Chem 282: 29521-29530.
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