Abstract
In Drosophila, it is thought that peptidoglycan recognition proteins (PGRPs) SA and LC structurally discriminate between bacterial peptidoglycans with lysine (Lys) or diaminopimelic (DAP) acid, respectively, thus inducing differential antimicrobial transcription response. Here, we find that accessibility to PG at the cell wall plays a central role in immunity to infection. When wall teichoic acids (WTAs) are genetically removed from S. aureus (Lys type) and Bacillus subtilis (DAP type), thus increasing accessibility, the binding of both PGRPs to either bacterium is increased. PGRP-SA and -LC double mutant flies are more susceptible to infection with both WTA-less bacteria. In addition, WTA-less bacteria grow better in PGRP-SA/-LC double mutant flies. Finally, infection with WTA-less bacteria abolishes any differential activation of downstream antimicrobial transcription. Our results indicate that accessibility to cell wall PG is a major factor in PGRP-mediated immunity and may be the cause for discrimination between classes of pathogens. It is widely believed that preference in recognition of structural features of bacterial peptidoglycan (PG) drives specificity in the Drosophila antibacterial response. Vaz et al. challenge this dogma by showing that accessibility to PG plays a central role in bacterial sensing and that structural discrimination is much less stringent than previously thought.
| Original language | English |
|---|---|
| Pages (from-to) | 2480-2492.e6 |
| Journal | Cell Reports |
| Volume | 27 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 21 May 2019 |
Fingerprint
Keywords
- B. subtilis
- Drosophila
- innate immunity
- peptidoglycan
- PGRPs
- S. aureus
- TagO
Cite this
}
Accessibility to Peptidoglycan Is Important for the Recognition of Gram-Positive Bacteria in Drosophila. / Vaz, Filipa; Kounatidis, Ilias; Covas, Gonçalo; Parton, Richard M.; Harkiolaki, Maria; Davis, Ilan; Filipe, Sergio Raposo; Ligoxygakis, Petros.
In: Cell Reports, Vol. 27, No. 8, 21.05.2019, p. 2480-2492.e6.Research output: Contribution to journal › Article
TY - JOUR
T1 - Accessibility to Peptidoglycan Is Important for the Recognition of Gram-Positive Bacteria in Drosophila
AU - Vaz, Filipa
AU - Kounatidis, Ilias
AU - Covas, Gonçalo
AU - Parton, Richard M.
AU - Harkiolaki, Maria
AU - Davis, Ilan
AU - Filipe, Sergio Raposo
AU - Ligoxygakis, Petros
N1 - info:eu-repo/grantAgreement/EC/FP7/310912/EU# info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F78748%2F2011/PT# info:eu-repo/grantAgreement/FCT/3599-PPCDT/129762/PT# BBSRC Project Grant BB/P005691/1; SFRH/BD/52207/2013 ; ONEIDA project LISBOA-01-0145-FEDER-016417; IF/01464/2013; Wellcome Trust Strategic Awards 091911/B/10/Z and 107457/Z/15/Z.
PY - 2019/5/21
Y1 - 2019/5/21
N2 - In Drosophila, it is thought that peptidoglycan recognition proteins (PGRPs) SA and LC structurally discriminate between bacterial peptidoglycans with lysine (Lys) or diaminopimelic (DAP) acid, respectively, thus inducing differential antimicrobial transcription response. Here, we find that accessibility to PG at the cell wall plays a central role in immunity to infection. When wall teichoic acids (WTAs) are genetically removed from S. aureus (Lys type) and Bacillus subtilis (DAP type), thus increasing accessibility, the binding of both PGRPs to either bacterium is increased. PGRP-SA and -LC double mutant flies are more susceptible to infection with both WTA-less bacteria. In addition, WTA-less bacteria grow better in PGRP-SA/-LC double mutant flies. Finally, infection with WTA-less bacteria abolishes any differential activation of downstream antimicrobial transcription. Our results indicate that accessibility to cell wall PG is a major factor in PGRP-mediated immunity and may be the cause for discrimination between classes of pathogens. It is widely believed that preference in recognition of structural features of bacterial peptidoglycan (PG) drives specificity in the Drosophila antibacterial response. Vaz et al. challenge this dogma by showing that accessibility to PG plays a central role in bacterial sensing and that structural discrimination is much less stringent than previously thought.
AB - In Drosophila, it is thought that peptidoglycan recognition proteins (PGRPs) SA and LC structurally discriminate between bacterial peptidoglycans with lysine (Lys) or diaminopimelic (DAP) acid, respectively, thus inducing differential antimicrobial transcription response. Here, we find that accessibility to PG at the cell wall plays a central role in immunity to infection. When wall teichoic acids (WTAs) are genetically removed from S. aureus (Lys type) and Bacillus subtilis (DAP type), thus increasing accessibility, the binding of both PGRPs to either bacterium is increased. PGRP-SA and -LC double mutant flies are more susceptible to infection with both WTA-less bacteria. In addition, WTA-less bacteria grow better in PGRP-SA/-LC double mutant flies. Finally, infection with WTA-less bacteria abolishes any differential activation of downstream antimicrobial transcription. Our results indicate that accessibility to cell wall PG is a major factor in PGRP-mediated immunity and may be the cause for discrimination between classes of pathogens. It is widely believed that preference in recognition of structural features of bacterial peptidoglycan (PG) drives specificity in the Drosophila antibacterial response. Vaz et al. challenge this dogma by showing that accessibility to PG plays a central role in bacterial sensing and that structural discrimination is much less stringent than previously thought.
KW - B. subtilis
KW - Drosophila
KW - innate immunity
KW - peptidoglycan
KW - PGRPs
KW - S. aureus
KW - TagO
UR - http://www.scopus.com/inward/record.url?scp=85065556787&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2019.04.103
DO - 10.1016/j.celrep.2019.04.103
M3 - Article
VL - 27
SP - 2480-2492.e6
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 8
ER -