Staphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during Infection
Caspase-3 controls the apoptotic pathway, a form of programmed cell death designed to be immunologically silent. Polymorphisms leading to reduced caspase-3 activity are associated with variable effects on tumorigenesis and yet arise frequently. Staphylococcus aureus is a human commensal and a freque...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
American Society for Microbiology
2019-11-01
|
Series: | mBio |
Subjects: | |
Online Access: | https://doi.org/10.1128/mBio.02270-19 |
id |
doaj-96116d89a9d742e78281597ee806214a |
---|---|
record_format |
Article |
spelling |
doaj-96116d89a9d742e78281597ee806214a2021-07-02T12:40:01ZengAmerican Society for MicrobiologymBio2150-75112019-11-01106e02270-1910.1128/mBio.02270-19Staphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during InfectionVolker WinstelOlaf SchneewindDominique MissiakasCaspase-3 controls the apoptotic pathway, a form of programmed cell death designed to be immunologically silent. Polymorphisms leading to reduced caspase-3 activity are associated with variable effects on tumorigenesis and yet arise frequently. Staphylococcus aureus is a human commensal and a frequent cause of soft tissue and bloodstream infections. Successful commensalism and virulence can be explained by the secretion of a plethora of immune evasion factors. One such factor, AdsA, destroys phagocytic cells by exploiting the apoptotic pathway. However, human CASP3 variants with loss-of-function alleles shield phagocytes from AdsA-mediated killing. This finding raises the possibility that some caspase-3 alleles may arise from exposure to S. aureus and other human pathogens that exploit the apoptotic pathway for infection.Staphylococcus aureus is a deadly pathogen that causes fatal diseases in humans. During infection, S. aureus secretes nuclease (Nuc) and adenosine synthase A (AdsA) to generate cytotoxic deoxyadenosine (dAdo) from neutrophil extracellular traps which triggers noninflammatory apoptosis in macrophages. In this manner, replicating staphylococci escape phagocytic killing without alerting the immune system. Here, we show that mice lacking caspase-3 in immune cells exhibit increased resistance toward S. aureus. Caspase-3-deficient macrophages are resistant to staphylococcal dAdo and gain access to abscess lesions to promote bacterial clearance in infected animals. We identify specific single nucleotide polymorphisms in CASP3 as candidate human resistance alleles that protect macrophages from S. aureus-derived dAdo, raising the possibility that the allelic repertoire of caspase-3 may contribute to the outcome of S. aureus infections in humans.https://doi.org/10.1128/mBio.02270-19staphylococcus aureusadenosine synthase a (adsa)caspase-3deoxyadenosineneutrophil extracellular traps (nets) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Volker Winstel Olaf Schneewind Dominique Missiakas |
spellingShingle |
Volker Winstel Olaf Schneewind Dominique Missiakas Staphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during Infection mBio staphylococcus aureus adenosine synthase a (adsa) caspase-3 deoxyadenosine neutrophil extracellular traps (nets) |
author_facet |
Volker Winstel Olaf Schneewind Dominique Missiakas |
author_sort |
Volker Winstel |
title |
Staphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during Infection |
title_short |
Staphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during Infection |
title_full |
Staphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during Infection |
title_fullStr |
Staphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during Infection |
title_full_unstemmed |
Staphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during Infection |
title_sort |
staphylococcus aureus exploits the host apoptotic pathway to persist during infection |
publisher |
American Society for Microbiology |
series |
mBio |
issn |
2150-7511 |
publishDate |
2019-11-01 |
description |
Caspase-3 controls the apoptotic pathway, a form of programmed cell death designed to be immunologically silent. Polymorphisms leading to reduced caspase-3 activity are associated with variable effects on tumorigenesis and yet arise frequently. Staphylococcus aureus is a human commensal and a frequent cause of soft tissue and bloodstream infections. Successful commensalism and virulence can be explained by the secretion of a plethora of immune evasion factors. One such factor, AdsA, destroys phagocytic cells by exploiting the apoptotic pathway. However, human CASP3 variants with loss-of-function alleles shield phagocytes from AdsA-mediated killing. This finding raises the possibility that some caspase-3 alleles may arise from exposure to S. aureus and other human pathogens that exploit the apoptotic pathway for infection.Staphylococcus aureus is a deadly pathogen that causes fatal diseases in humans. During infection, S. aureus secretes nuclease (Nuc) and adenosine synthase A (AdsA) to generate cytotoxic deoxyadenosine (dAdo) from neutrophil extracellular traps which triggers noninflammatory apoptosis in macrophages. In this manner, replicating staphylococci escape phagocytic killing without alerting the immune system. Here, we show that mice lacking caspase-3 in immune cells exhibit increased resistance toward S. aureus. Caspase-3-deficient macrophages are resistant to staphylococcal dAdo and gain access to abscess lesions to promote bacterial clearance in infected animals. We identify specific single nucleotide polymorphisms in CASP3 as candidate human resistance alleles that protect macrophages from S. aureus-derived dAdo, raising the possibility that the allelic repertoire of caspase-3 may contribute to the outcome of S. aureus infections in humans. |
topic |
staphylococcus aureus adenosine synthase a (adsa) caspase-3 deoxyadenosine neutrophil extracellular traps (nets) |
url |
https://doi.org/10.1128/mBio.02270-19 |
work_keys_str_mv |
AT volkerwinstel staphylococcusaureusexploitsthehostapoptoticpathwaytopersistduringinfection AT olafschneewind staphylococcusaureusexploitsthehostapoptoticpathwaytopersistduringinfection AT dominiquemissiakas staphylococcusaureusexploitsthehostapoptoticpathwaytopersistduringinfection |
_version_ |
1721329939518586880 |