PMID- 34702812
OWN - NLM
STAT- MEDLINE
DCOM- 20211130
LR  - 20230207
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Oct 26
TI  - The cell envelope of Staphylococcus aureus selectively controls the sorting of 
      virulence factors.
PG  - 6193
LID - 10.1038/s41467-021-26517-z [doi]
LID - 6193
AB  - Staphylococcus aureus bi-component pore-forming leukocidins are secreted toxins 
      that directly target and lyse immune cells. Intriguingly, one of the leukocidins, 
      Leukocidin AB (LukAB), is found associated with the bacterial cell envelope in 
      addition to secreted into the extracellular milieu. Here, we report that 
      retention of LukAB on the bacterial cells provides S. aureus with a 
      pre-synthesized active toxin that kills immune cells. On the bacteria, LukAB is 
      distributed as discrete foci in two distinct compartments: membrane-proximal and 
      surface-exposed. Through genetic screens, we show that a membrane lipid, 
      lysyl-phosphatidylglycerol (LPG), and lipoteichoic acid (LTA) contribute to LukAB 
      deposition and release. Furthermore, by studying non-covalently surface-bound 
      proteins we discovered that the sorting of additional exoproteins, such as IsaB, 
      Hel, ScaH, and Geh, are also controlled by LPG and LTA. Collectively, our study 
      reveals a multistep secretion system that controls exoprotein storage and protein 
      translocation across the S. aureus cell wall.
CI  - (c) 2021. The Author(s).
FAU - Zheng, Xuhui
AU  - Zheng X
AD  - Department of Microbiology, New York University Grossman School of Medicine, New 
      York, New York, USA.
FAU - Marsman, Gerben
AU  - Marsman G
AUID- ORCID: 0000-0002-5376-8000
AD  - Department of Cellular Microbiology, Max Planck Institute for Infection Biology, 
      Berlin, Germany.
FAU - Lacey, Keenan A
AU  - Lacey KA
AUID- ORCID: 0000-0002-9242-0170
AD  - Department of Microbiology, New York University Grossman School of Medicine, New 
      York, New York, USA.
FAU - Chapman, Jessica R
AU  - Chapman JR
AUID- ORCID: 0000-0002-4080-8667
AD  - The Proteomics Laboratory, Division of Advanced Research Technologies, New York 
      University Grossman School of Medicine, New York, New York, USA.
FAU - Goosmann, Christian
AU  - Goosmann C
AD  - Department of Cellular Microbiology, Max Planck Institute for Infection Biology, 
      Berlin, Germany.
FAU - Ueberheide, Beatrix M
AU  - Ueberheide BM
AD  - The Proteomics Laboratory, Division of Advanced Research Technologies, New York 
      University Grossman School of Medicine, New York, New York, USA.
AD  - Department of Biochemistry and Molecular Pharmacology, New York University 
      Grossman School of Medicine, New York, USA.
FAU - Torres, Victor J
AU  - Torres VJ
AUID- ORCID: 0000-0002-7126-0489
AD  - Department of Microbiology, New York University Grossman School of Medicine, New 
      York, New York, USA. Victor.Torres@nyulangone.org.
LA  - eng
GR  - R01 AI099394/AI/NIAID NIH HHS/United States
GR  - R01 AI140754/AI/NIAID NIH HHS/United States
GR  - R01 AI105129/AI/NIAID NIH HHS/United States
GR  - HHSN272201400019C/AI/NIAID NIH HHS/United States
GR  - P30 CA016087/CA/NCI NIH HHS/United States
GR  - S10 OD010582/OD/NIH HHS/United States
GR  - HHSN272200700055C/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211026
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cytotoxins)
RN  - 0 (Leukocidins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Phosphatidylglycerols)
RN  - 0 (Teichoic Acids)
RN  - 0 (Virulence Factors)
RN  - 0 (leukocidin AB, Staphylococcus aureus)
RN  - 42241-11-2 (lysylphosphatidylglycerol)
RN  - 56411-57-5 (lipoteichoic acid)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/metabolism/toxicity
MH  - Cell Membrane/*metabolism
MH  - Cell Wall/*metabolism
MH  - Cytotoxins/metabolism/toxicity
MH  - Humans
MH  - Leukocidins/metabolism/toxicity
MH  - Lipopolysaccharides/genetics/metabolism
MH  - Lysine/genetics/metabolism
MH  - Mice
MH  - Phagocytes/drug effects
MH  - Phosphatidylglycerols/genetics/metabolism
MH  - Protein Transport
MH  - Staphylococcal Infections/microbiology
MH  - Staphylococcus aureus/genetics/*metabolism
MH  - Teichoic Acids/genetics/metabolism
MH  - Virulence Factors/*metabolism/toxicity
PMC - PMC8548510
COIS- V.J.T. is an inventor on patents and patent applications filed by New York 
      University, which are currently under commercial license to Janssen Biotech Inc. 
      (patent nos. US10669329; US10202440; US10087243; MY-175062-A; BR112013032774-0; 
      60 2014 068 192.1; 40000719B; 1190640B9; 10-2050267; 2012273125; 2012273123; 
      10,781,246; 10,301,378; 9,783,597; 9,657,103; 9,644,023; 9,481,723; 9,480,726; 
      9,091,689; 8,846,609; 6758363; 6452765; 6,170,913; 6,093,760; 3441474; 3403669; 
      3011012; 2,720,754; 2720714; 2,635,462; 2,613,135; 2,609,650; 730359; 710,439; 
      619,942; 619,938; 357,938; 343,589; 340,446; and 229922). Janssen Biotech Inc. 
      provides research funding and other payments associated with the licensing 
      agreement. All other authors declare no conflicts of interest.
EDAT- 2021/10/28 06:00
MHDA- 2021/12/01 06:00
PMCR- 2021/10/26
CRDT- 2021/10/27 06:15
PHST- 2020/10/27 00:00 [received]
PHST- 2021/10/05 00:00 [accepted]
PHST- 2021/10/27 06:15 [entrez]
PHST- 2021/10/28 06:00 [pubmed]
PHST- 2021/12/01 06:00 [medline]
PHST- 2021/10/26 00:00 [pmc-release]
AID - 10.1038/s41467-021-26517-z [pii]
AID - 26517 [pii]
AID - 10.1038/s41467-021-26517-z [doi]
PST - epublish
SO  - Nat Commun. 2021 Oct 26;12(1):6193. doi: 10.1038/s41467-021-26517-z.