Principle Areas of Study
Development of pathogen specific antimicrobials
Although antimicrobials continue to provide important treatment options for a wide variety of infectious diseases, most antibiotics do not specifically eliminate pathogens. As a result, while exposure to antibiotics can kill an offending pathogen, this treatment also causes the death of many “good” microbes. This may not only have a negative impact on immune responsiveness to potential pathogens, but can also result in a wide variety of additional undesired outcomes.
The inability of antimicrobials to specifically kill pathogens is most often due to the common expression of the targets they utilize, which while present in pathogens, also occur in a broad range of “good” microbes. In contrast to traditional antimicrobial targets, cell surface carbohydrates can vary significantly between “good” microbes and potential pathogens, providing a potential target to selectively remove pathogens without impacting “good” microbes. We recently discovered a group of carbohydrate binding proteins, galectins, that possess the unique capacity to specifically kill microbes following engagement of microbial carbohydrates. As a result, we are engineering galectins to develop novel antimicrobials that specifically recognize and kill pathogens through recognition of distinct cell surface carbohydrates, while leaving “good” bacteria unaffected.
Members of lab studying this area
Connie Arthur, Seema Patel, Anna Blenda, Nourine Ahmed, Christian Gerner-Smidt, Jianmei Wang
- Stowell SR, Arthur CM, McBride R, Berger O, Razi N, Heimburg- Molinaro J, Rodrigues LC, Gourdine JP, Noll AJ, von Gunten S, Smith DF, Knirel YA, Paulson JC, Cummings RD. Microbial glycan microarray defines key features of host-microbial interactions. Nat Chem Biol 2014 Jun;10(6):470-6
- Stowell SR, Arthur CM, Dias-Baruffi M, Rodrigues LC, Gourdine JP, Heimburg-Molinaro J, Ju T, Molinaro RJ, Rivera-Marrero C, Xia B, Smith DF, Cummings RD. Innate immune lectins kills bacteria expressing blood group antigen. Nature Medicine 2010 Mar; 16(3):295-301
- Arthur CM, Patel SR, Mener A, Kamili NA, Fasano RM, Meyer E, Winkler AM, Sola-Visner M, Josephson CD and Stowell SR*. Innate Immunity against molecular mimicry: Examining galectin-mediated antimicrobial activity. Bioessays 2015 Dec; 37(12):1327-1337