PXD055534-1

PXD055534 is an original dataset announced via ProteomeXchange.

Title	Streptococcal S protein is a coordinator of cell wall repair and defense against host antimicrobials
Description	Pathogenic bacteria have acquired the ability to resist antibacterial defense mechanisms of the host. Streptococci are common in animal microbiota and include opportunistic pathogens like Group A Streptococcus (GAS) and Streptococcus pneumoniae (pneumococcus). While the conserved streptococcal S protein has been identified as a key factor in GAS virulence, its exact function is unclear. Here, we show that the pneumococcal S protein is crucial for resisting against host-derived antimicrobials by coordinating cell wall modification and repair. Specifically, we show that S proteins are septally localized through their transmembrane domain and contain an extracellular peptidoglycan (PG) binding LysM domain which is required for its function. Protein-protein and genetic interaction studies demonstrate that the pneumococcal S protein directly interacts with a PG synthase, class A penicillin binding protein PBP1a, and the PG deacetylase PgdA. Single molecule experiments reveal that the fraction of circumferentially moving PBP1a molecules is reduced in the absence of S protein. Consistent with an impaired PBP1a function, streptococci lacking S protein exhibit increased susceptibility to cell wall targeting antibiotics and altered cell morphologies. PG analysis showed reduced N-deacetylation of glycans in the S. pneumoniae S protein mutant, indicating reduced PgdA activity. We show that pneumococci lacking the S protein cannot persist transient penicillin treatment, are more susceptible to the human antimicrobial peptide LL-37 and to lysozyme, and show decreased virulence in zebrafish and mice. Our data support a model in which S proteins activate regulate PBP1a activity and play a key role in coordinating PG repair and modification. This cell wall ‘sentinel’ control system provides defense against host-derived and environmental antimicrobial attack.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-07_16:09:20.125.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD055534
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jan-Willem Veening
SpeciesList	scientific name: Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466); NCBI TaxID: NEWT:373153;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-04 01:47:58	ID requested
⏵ 1	2026-06-07 16:09:20	announced

Burnier J, Gallay C, Bruce KE, Bj, å, nes E, Martin L, Jim KK, Tsui HT, Cremers AJH, Mignolet J, Vollmer D, Biboy J, Nizet V, Vollmer W, Winkler ME, Veening JW, Pneumococcal S protein coordinates cell wall modification and repair to resist host antimicrobials. Nat Microbiol, 11(1):282-300(2026) [pubmed]

10.1038/s41564-025-02184-4;

10.6019/PXD055534;

submitter keyword: S-protein, cell wall repair, Streptococcus pneumoniae, penicillin-binding protein

Jan-Willem Veening
contact affiliation	Quartier UNIL-Sorge Bâtiment Biophore Bureau : 2455 CH-1015 Lausanne
contact email	jan-willem.veening@unil.ch
lab head
Jan-Willem Veening
contact affiliation	University of Lausanne
contact email	jan-willem.veening@unil.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055534
     1. Label: PRIDE project
     2. Name: Streptococcal S protein is a coordinator of cell wall repair and defense against host antimicrobials