<a href="https://departments.bryant.edu/science-and-technology/faculty/reid-christopher"><img src="https://departments.bryant.edu/sites/departments/files/2019-04/faculty-cas-science-technology-reid-460x460.jpg" alt="Christopher Reid" align="right" margin="10px" width="200px"></a>
Inhibition of Streptococcus Pneumoniae Autolysins Highlight Distinct Differences Between Chemical and Genetic Inactivation
Authors: Christopher Reid
<br>Despite renewed interest, development of chemical biology methods to study peptidoglycan metabolism has lagged in comparison to the glycobiology field in general. To address this, a panel of diamides were screened against the Gram-positive pathogen
Streptococcus pneumoniae
to identify inhibitors of bacterial growth. The screen identified the diamide fgkc as a narrow spectrum bacteriostatic inhibitor of
S. pneumoniae
growth with an MIC of 7.8 μM. The diamide inhibited detergent-induced autolysis in a concentration dependent manner indicating peptidoglycan degradation as the mode-of-action. Genetic screening of autolysin mutants suggested LytB, an endo-N-acetylglucosaminidase, involved in cell division as the potential target. Surprisingly, biochemical, and phenotypic analysis contradicted the genetic screen results. Phenotypic studies with the
Δlytb
strain illustrate the difference between genetic and chemical inactivation of autolysins. These findings suggest that meta-phenotypes including autolytic activity, cell morphology, and genetic screening can be the result of the complex interaction of one or more possible pathways that are connected to cell wall metabolism.