RESEARCH
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.
Determination of Accumulation in Bacteria
Multidrug-resistant (MDR) bacterial infections are widely recognized as one of the most urgent global health threats due to their high resistance to nearly all available antibiotics. The rising prevalence of infections caused by this pathogen severely limits treatment options and poses a significant challenge to modern healthcare systems. The primary obstacle in treating infections (especially diderm bacteria) lies in the bacterium’s unique outer membrane, which acts as a formidable barrier, preventing many antibiotics from reaching their intracellular targets. Despite the critical need for new antibiotics and adjuvants that can overcome this barrier, our understanding of the molecular rules that govern antibiotic accumulation into bacteria remains limited. Our lab aims to address this gap by developing and applying innovative high-throughput screening platforms designed to measure the accumulation of small molecules with subcellular resolution.
We co-lead the Center for Antibiotic Refinement via Accumulation Profiling (CARvAP)
Bacterial Cell Wall Probes
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.
Commensal Bacteria - Imaging and Connection to Brain Biology
Our group is building next-generation imaging techniques that will facilitate the imaging of gut commensal bacteria in live animals. The goal is to install specific handles on the surface of bacteria to illuminate a host's microbiota in a selective manner. Moreover, we are exploring ways that bacteria release metabolites to impact host neurobiology. We hypothesize that specific molecules are released that can modulate the function of neurotransmitters in a way that can impact human metal disorder and health.