Dataset Information

Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Streptococcus Pyogenes Mgas315 Streptococcus Pyogenes M1 Gas Homo Sapiens (human)

SUBMITTER: Thomas Sura

LAB HEAD: Doerte Becher

PROVIDER: PXD040160 | Pride | 2023-10-24

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	160805_iRT.fasta	Fasta
	190715_human_reference_uniprot_proteome_AUP000005640_reviewed.fasta	Fasta
	200129_QE1_PM1_ThS_NGNS_PS_PMN_5448_ON_01.raw	Raw
	200129_QE1_PM1_ThS_NGNS_PS_PMN_5448_ON_02.raw	Raw
	200129_QE1_PM1_ThS_NGNS_PS_PMN_5448_ON_03.raw	Raw

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Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes.

Shumba Patience P Sura Thomas T Moll Kirsten K Chakrakodi Bhavya B Tölken Lea A LA Hoßmann Jörn J Hoff Katharina J KJ Hyldegaard Ole O Nekludov Michael M Svensson Mattias M Arnell Per P Skrede Steinar S Norrby-Teglund Anna A Siemens Nikolai N

Journal of biomedical science 20230710 1

<h4>Background</h4>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.<h4>Methods</h4>Bacterial in ...[more]

PMID: 37430325

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