PXD040160-3

PXD040160 is an original dataset announced via ProteomeXchange.

Title	Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes
Description	Streptococcus pyogenes (group A streptococci; GAS) is the main causative pathogen of monomicrobial necrotizing soft tissue infections (NSTIs). To resist immuno-clearance, GAS adapt their genetic information and/or phenotype to the surrounding environment. Hyper-virulent streptococcal pyrogenic exotoxin B (SpeB) negative variants caused by covRS mutations are enriched during infection. A key driving force for this process is the bacterial Sda1 DNase. Here, we identify another strategy resulting in SpeB-negative variants, namely reversible abrogation of SpeB secretion triggered by neutrophil effector molecules. Analysis of NSTI patient tissue biopsies revealed that tissue inflammation, neutrophil influx, and degranulation positively correlate with increasing frequency of SpeB-negative GAS clones. Using single colony proteomics, we show that GAS isolated directly from tissue express but do not secrete SpeB. Once the tissue pressure is lifted, GAS regain SpeB secreting function. Neutrophils were identified as the main immune cells responsible for the observed phenotype. Subsequent analyses identified hydrogen peroxide and hypochlorous acid as reactive agents driving this phenotypic GAS adaptation to the tissue environment. SpeB-negative GAS show improved survival within neutrophils and induce increased degranulation. Our findings provide new information about GAS fitness and heterogeneity in the soft tissue milieu and provide new potential targets for therapeutic intervention in NSTIs.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:09:57.743.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Sura
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Streptococcus pyogenes M1 GAS; NCBI TaxID: 160490; scientific name: Streptococcus pyogenes MGAS315; NCBI TaxID: 198466;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-16 09:50:17	ID requested
1	2023-10-24 12:44:53	announced
2	2023-11-14 09:10:33	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:09:59	announced	2024-10-22: Updated project metadata.

Shumba P, Sura T, Moll K, Chakrakodi B, T, ö, lken LA, Ho, ß, mann J, Hoff KJ, Hyldegaard O, Nekludov M, Svensson M, Arnell P, Skrede S, Norrby-Teglund A, Siemens N, Hedetoft M, Bruun T, Oppegaard O, Nedreb, ø T, Rath E, Madsen MB, Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes. J Biomed Sci, 30(1):52(2023) [pubmed]

10.1186/s12929-023-00947-x;

submitter keyword: SpeB, necrotizing soft tissue infections, neutrophils,Streptococcus pyogenes

Doerte Becher
contact affiliation	Department of Microbial Proteomics, Institute of Microbiology, University of Greifswald, Greifswald, Germany
contact email	dbecher@uni-greifswald.de
lab head
Thomas Sura
contact affiliation	University of Greifswald, Center for Functional Genomics of Microbes, Institute of Microbiology, Department of Microbial Proteomics
contact email	thomas.sura@uni-greifswald.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040160
     1. Label: PRIDE project
     2. Name: Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes