B.S. Ithaca College, 2003
Ph.D. Purdue University, 2009
NIH Postdoctoral Fellow, University of Pennsylvania, 2009-2011
The Pires lab uses synthetic chemistry as a platform to construct cell wall analogs that metabolically label live bacteria and mimic key aspects of cell wall architecture. Through this work, the interrogation of cell wall remodeling and processing in pathogenic bacteria will guide the design of next-generation antibiotics that circumvent resistance mechanisms. Moreover, we are working to establish the fundamental framework of a non-traditional antibiotic therapy based on the specific recruitment of components of the immune cells to target the destruction of pathogenic bacteria.
Every year in the United States, over two million people are afflicted with bacterial infections resistant to FDA-approved antibiotics. In order to counter the rapid rise in drug-resistance in bacteria, new drug targets and diagnostic tests are urgently needed. The bacterial cell wall has proven to be a rich source of antibiotic drug discovery. However, there are fundamental aspects of bacterial cell wall assembly and its interaction with the host organism that are yet to be fully elucidated.
Bacterial Cell Wall Probes – Chemical Microbiology
The Pires laboratory will leverage the laboratory expertise in building synthetic bacterial cell wall mimics to reveal key aspects of peptidoglycan recognition and cell wall remodeling. We anticipate that interrogation of cell wall remodeling and processing in pathogenic bacteria will guide the design of next-generation antibiotics that circumvent resistance mechanisms. Our work has yielded synthetic cell wall mimics that reveal how bacterial cell wall building blocks regulate surface remodeling and biosynthesis.
Synthetic Immunotherapeutics Against Bacterial Pathogens
We are developing unique antimicrobial therapeutic strategies based on a specific modulation of the immune response to combat bacterial infections. We have established novel methods to re-engage components of the immune system to induce a targeted immunological response to the site of infection. The goal is to assemble and evaluate agents that induce the recruitment of antibodies or the direct engagement with human immune cells. This new class of agents will constitute a way of mobilizing the immune system to target poorly immunogenic bacterial pathogens.
Induction of Endogenous Antibody Recruitment to the Surface of the Pathogen Enterococcus faecium. Dalesandro B & Pires MM. ACS Infect Dis. 2020 Nov 12 (ASAP).
Facile Synthesis and Metabolic Incorporation of m-DAP Bioisosteres Into Cell Walls of Live Bacteria. Apostolos A, Nelson J, Silva J, Lameira J, Achimovich A, Gahlmann A, Alves C & Pires MM. ACS Chem Biol. 2020 Nov 20;15(11):2966-2975.
Remodeling of Cross-bridges Controls Peptidoglycan Cross-linking Levels in Bacterial Cell Walls. Apostolos A, Pidgeon S & Pires MM. ACS Chem Biol. 2020 May 15;15(5):1261-1267.
pH-Dependent Grafting of Cancer Cells with Antigenic Epitopes Promotes Selective Antibody-Mediated Cytotoxicity. Wehr J, Sikorski E, Bloch E, Feigman M, Ferraro N, Baybutt T, Snook A, Pires MM & Thevenin D. J Med Chem. 2020 Apr 9;63(7):3713-3722.
Generalized Heterodyne Configurations for Photoinduced Force Microscopy. Wang L, Jakob DS, Wang H, Apostolos A, Pires MM, Xu XG. Anal Chem. 2019 Oct 15;91(20):13251-13259.
L,D-Transpeptidase Specific Probe Reveals Spatial Activity of Peptidoglycan Cross-Linking. Pidgeon SE, Apostolos AJ, Nelson JM, Shaku M, Rimal B, Islam MN, Crick DC, Kim SJ, Pavelka MS, Kana BD, Pires MM. ACS Chem Biol. 2019 Oct 18;14(10):2185-2196.
Insight into Elongation Stages of Peptidoglycan Processing in Bacterial Cytoplasmic Membranes. Kim S, Pires MM, Im W. Sci Rep. 2018 Dec 7;8(1):17704.
Synthetic Immunotherapeutics against Gram-negative Pathogens. Feigman MS, Kim S, Pidgeon SE, Yu Y, Ongwae GM, Patel DS, Regen S, Im W, Pires MM. Cell Chem Biol. 2018 Oct 18;25(10):1185-1194.e5.
Synthetic Immunobiotics: A Future Success Story in Small Molecule-Based Immunotherapy? Feigman MJS, Pires MM. ACS Infect Dis. 2018 May 11;4(5):664-672.