New Paper: The Slr protein of Streptococcus pyogenes is selectively expressed in vivo and is a target for protective antibodies

Research led by Matevz Rumpret (Postdoc) and Jonas Lannergard (Lund University) together with Gunnar Lindahl, has been published in June 2025 in EMBO Molecular Medicine. https://pubmed.ncbi.nlm.nih.gov/42298213/

The standard approach to search for bacterial antigens for vaccination is to grow the bacteria in lab broth, analyse the proteins on their surface, and select key candidates. However, bacteria can behave differently during lab culture compared to during colonisation or infection in a human host. Therefore, if a bacterial factor is only expressed in the host, traditional lab screens miss it entirely.

We set out to investigate Slr, a surface lipoprotein present across all strains of Streptococcus pyogenes (Group A Streptococcus), a major human pathogen responsible for everything from strep throat to life-threatening invasive infections. We found that the Slr protein is completely absent from the bacterial surface during standard laboratory growth in nutrient broth. We also uncovered that Slr expression is governed by the regulator AdcR, indicative that in host environment that are low in zinc, this regulatory switch turns on and Slr is expressed. In mouse models of infection, targeting Slr triggered protective antibody responses. We also found that antibody responses were almost exclusively directed at a specific region of Slr containing histidine triad (HT) motifs. By demonstrating that Slr can generate protective immunity during infection, our study shows why it is important to study bacterial factors expressed in vivo and highlight Slr as a vaccine candidate for S. pyogenes.

The Slr protein of Streptococcus pyogenes is selectively expressed in vivo and is a target for protective antibodies. Rumpret M, Lannergård J, Kristensen BM, Lynskey NN, Bowen C, Johnsson E, Nilsson OR, Norrby-Teglund A, Stålhammar-Carlemalm M, Lindahl G, McCarthy AJ.

EMBO Mol Med. 2026 Jun 15. doi: 10.1038/s44321-026-00470-0.