A1 Journal article (refereed)
Reassessing the substrate specificities of the major Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM (2024)

Antenucci, L., Virtanen, S., Thapa, C., Jartti, M., Pitkänen, I., Tossavainen, H., & Permi, P. (2024). Reassessing the substrate specificities of the major Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM. eLife, 13, Article RP93673. https://doi.org/10.7554/eLife.93673

JYU authors or editors

Publication details

All authors or editors: Antenucci, Lina; Virtanen, Salla; Thapa, Chandan; Jartti, Minne; Pitkänen, Ilona; Tossavainen, Helena; Permi, Perttu

Journal or series: eLife

eISSN: 2050-084X

Publication year: 2024

Publication date: 04/11/2024

Volume: 13

Article number: RP93673

Publisher: eLife Sciences Publications

Publication country: United Kingdom

Publication language: English

DOI: https://doi.org/10.7554/eLife.93673

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/98278

Web address of parallel published publication (pre-print): https://doi.org/10.1101/2023.10.13.562287

Abstract

Orchestrated action of peptidoglycan (PG) synthetases and hydrolases is vital for bacterial growth and viability. Although the function of several PG synthetases and hydrolases is well understood, the function, regulation, and mechanism of action of PG hydrolases characterised as lysostaphin-like endopeptidases have remained elusive. Many of these M23 family members can hydrolyse glycyl-glycine peptide bonds and show lytic activity against Staphylococcus aureus whose PG contains a pentaglycine bridge, but their exact substrate specificity and hydrolysed bonds are still vaguely determined. In this work, we have employed NMR spectroscopy to study both the substrate specificity and the bond cleavage of the bactericide lysostaphin and the S. aureus PG hydrolase LytM. Yet, we provide substrate-level evidence for the functional role of these enzymes. Indeed, our results show that the substrate specificities of these structurally highly homologous enzymes are similar, but unlike observed earlier both LytM and lysostaphin prefer the D-Ala-Gly cross-linked part of mature peptidoglycan. However, we show that while lysostaphin is genuinely a glycyl-glycine hydrolase, LytM can also act as a D-alanyl-glycine endopeptidase.

Keywords: infectious diseases; NMR spectroscopy; staphylococci; microbiology; bacteriology; biochemistry

Free keywords: LytM; NMR spectroscopy; S. aureus; biochemistry; chemical biology; infectious disease; lysostaphin; microbiology; peptidoglycan hydrolases; substrate specificity.

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Ministry reporting: Yes

VIRTA submission year: 2024

Preliminary JUFO rating: 2