An activity-based probe targeting the streptococcal virulence factor C5a peptidase

• Published in: Chemical communications (Cambridge, England) Vol. 58; no. 58; pp. 8113 - 8116
• Main Authors: Krishnamoorthy, Sankarganesh, Steiger, Andrea K, Nelson, William C, Egbert, Robert G, Wright, Aaron T
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 19.07.2022; Royal Society of Chemistry; Royal Society of Chemistry (RSC)
• Subjects: Chemistry; Chemistry, Multidisciplinary; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Microorganisms; Pathogens; Peptidases; Physical Sciences; Science & Technology; Virulence
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/d2cc01517j

Development of profiling strategies to provide high resolution understanding of enzymes involved in bacterial infections remains an important need. These strategies help resolve enzyme mechanisms of actions and can guide therapeutic development. We have developed a selective new activity-based probe (ABP) targeting a highly conserved surface bound enzyme, C5a peptidase, present in several pathogenic Streptococci . We demonstrate our probe inhibits C5a peptidase activity and enables detection of C5a peptidase expressing pathogens in microbial mixtures. Our profiling strategy selectively labels the pathogen by phenotype and enables specific isolation of the live bacteria providing a route for further in-depth investigation. This study paves the way towards a rapid detection, isolation, and characterization pipeline for existing and emerging strains of most common pathogenic Streptococci . A selective activity-based probe for C5a peptidase profiles pathogenic streptococci .