The Pires' Research group synthesized analogs of cell walls and established that they are tolerated by bacteria, which provided an efficient way to graft handles on bacterial cell surfaces. With these concepts defined, they showed that this mode of grafting antigens onto bacterial cell surfaces was superior to their original concept. Their work was published in 2016 in the journal ACS Infectious Diseases without a request for any further revisions. The editor-in-chief invited their work to be highlighted as the journal cover to bring higher visibility to this emerging and novel modality of fighting bacterial infections.
Their research team has also described chemical probes that label bacterial cell walls of live organisms to report on structural alterations linked with antibiotic resistance. The improper use of vancomycin has directly led to the rise in Vancomycin Resistant Enterococci (VRE). VRE cells gain resistance to vancomycin by synthesizing altered cell wall building blocks. Although structurally subtle, the changes to the cell wall result in 1000-fold weaker binding affinity to vancomycin. The drug-resistant phenotype specific to vancomycin requires the function of two primary genes. The product on one of the genes is responsible for degrading drug-sensitive cell wall building blocks. Both of these enzymatic functions are necessary for VRE. In 2017, they published successive articles in:
ACS Chemical Biology and Angewandte Chemie, which disclosed their specific probes to each pathway. Their work was also selected and highlighted by C&EN magazine in June 2017.
Dr. Pires presented invited talks at NIH-Chemical Biology Laboratory, Temple University, New York University, Kutztown University, Drew University, North Carolina State University, and Johns Hopkins.
Additionally, he presented his work at five conferences: “Frontiers at the Chemistry-Biology Interface” Symposium at the University of Delaware; Lehigh University Workshop-“Taking Aim at Bacteria”; New York Academy of Science-“Emerging Paradigms in Chemical Biology”; National Meeting of the American Chemical Society in Philadelphia and at the Protein Society National Meeting in Montreal.
The research group had the following publications:
Fura, J.; Pidgeon, S.; Birabaharan, M. and Pires, M. “Dipeptide-Based Metabolic Labeling of Bacterial Cells for Endogenous Antibody Recruitment” ACS Infectious Diseases 2016, 2, 302-309. (Chosen as the cover).
Yu, Y; Sabulski, M.; Schell, W.; Pires, M.; Perfect, J. and Regen, S. “Simple Strategy for Taming Membrane-Disrupting Antibiotics” Bioconjugate Chemistry 2016, 27, 2850-2853. (Highlighted by Chemical & Engineering News).
Fura, J.; Sarkar, S.; Pidgeon, S. and Pires, M. “Combatting Bacterial Pathogens with Immunomodulation and Infection Tolerance Strategies” Current Topics in Medicinal Chemistry 2017, 17, 290-304.
Pidgeon, S. and Pires, M. “Cell Wall Remodeling by a Synthetic Analog Reveals Metabolic Adaptation in Vancomycin Resistant Enterococci” Angewandte Chemie Int. Engl. 2017, in press (Highlighted by Chemical & Engineering News.)
Pidgeon, S. and Pires, M. “Vancomycin-dependent Response in Live Drug-Resistant Bacteria via Metabolic Labeling” ACS Chemical Biology 2017, in press (Highlighted by Chemical & Engineering News.)