Expanded profiling of β-lactam selectivity for penicillin-binding proteins in Streptococcus pneumoniae D39

Deepti Sharan, Erin E. Carlson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Penicillin-binding proteins (PBPs) are integral to bacterial cell division as they mediate the final steps of cell wall maturation. Selective fluorescent probes are useful for understanding the role of individual PBPs, including their localization and activity during growth and division of bacteria. For the development of new selective probes for PBP imaging, several β-lactam antibiotics were screened, as they are known to covalently bind PBP in vivo. The PBP inhibition profiles of 16 commercially available β-lactam antibiotics were evaluated in an unencapsulated derivative of the D39 strain of Streptococcus pneumoniae, IU1945. These β-lactams have not previously been characterized for their PBP inhibition profiles in S. pneumoniae and these data augment those obtained from a library of 20 compounds that we previously reported. We investigated seven penicillins, three carbapenems, and six cephalosporins. Most of these β-lactams were found to be co-selective for PBP2x and PBP3, as was noted in our previous studies. Six out of 16 antibiotics were selective for PBP3 and one molecule was co-selective for PBP1a and PBP3. Overall, this work expands the chemical space available for development of future β-lactam-based probes for specific pneumococcal PBP labeling and these methods can be used for the development of probes for PBP labelling in other bacterial species.

Original languageEnglish (US)
Pages (from-to)433-443
Number of pages11
JournalBiological Chemistry
Issue number4
StatePublished - Mar 1 2022

Bibliographical note

Funding Information:
The authors thank the Malcolm Winkler Lab at Indiana University for providing S. pneumoniae strains, and the rest of the Carlson Lab for helpful discussion and support. This work was supported by the National Institutes of Health (GM140486-01) and the University of Minnesota, Department of Chemistry.

Publisher Copyright:
© 2022 Walter de Gruyter GmbH, Berlin/Boston.


  • activity-based probes
  • antibiotics
  • penicillin-binding proteins
  • β-lactams

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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