Staphylococcus aureus uses the ArlRS and MgrA cascade to regulate immune evasion during skin infection.
Animals
Bacterial Adhesion
Bacterial Proteins
/ metabolism
Cell Death
Chemotaxis
Extracellular Traps
/ metabolism
Imaging, Three-Dimensional
Immune Evasion
Mice, Inbred C57BL
Models, Biological
Mutation
/ genetics
Neutrophils
/ metabolism
Phagocytosis
Reactive Oxygen Species
/ metabolism
Skin
/ microbiology
Staphylococcal Infections
/ immunology
Staphylococcus aureus
/ immunology
Virulence
alpha-Defensins
/ metabolism
Staphylococcus aureus
abscess
gene regulation
immune evasion
innate immunity
intravital microscopy
neutrophil
skin infection
surface proteins
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
27 07 2021
27 07 2021
Historique:
received:
21
10
2020
revised:
01
05
2021
accepted:
09
07
2021
entrez:
28
7
2021
pubmed:
29
7
2021
medline:
10
2
2022
Statut:
ppublish
Résumé
Skin is one of the most common sites of host immune response against Staphylococcus aureus infection. Here, through a combination of in vitro assays, mouse models, and intravital imaging, we find that S. aureus immune evasion in skin is controlled by a cascade composed of the ArlRS two-component regulatory system and its downstream effector, MgrA. S. aureus lacking either ArlRS or MgrA is less virulent and unable to form correct abscess structure due to de-repression of a giant surface protein, Ebh. These S. aureus mutants also have decreased expression of immune evasion factors (leukocidins, chemotaxis-inhibitory protein of S. aureus [CHIPS], staphylococcal complement inhibitor [SCIN], and nuclease) and are unable to kill neutrophils, block their chemotaxis, degrade neutrophil extracellular traps, and survive direct neutrophil attack. The combination of disrupted abscess structure and reduced immune evasion factors makes S. aureus susceptible to host defenses. ArlRS and MgrA are therefore the main regulators of S. aureus immune evasion and promising treatment targets.
Identifiants
pubmed: 34320352
pii: S2211-1247(21)00885-8
doi: 10.1016/j.celrep.2021.109462
pmc: PMC8450000
mid: NIHMS1728475
pii:
doi:
Substances chimiques
Bacterial Proteins
0
Reactive Oxygen Species
0
alpha-Defensins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
109462Subventions
Organisme : BLRD VA
ID : I01 BX002711
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141490
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI153185
Pays : United States
Organisme : CIHR
ID : FDN-143248
Pays : Canada
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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