Accessibility to Peptidoglycan Is Important for the Recognition of Gram-Positive Bacteria in Drosophila

Filipa Vaz, Ilias Kounatidis, Gonçalo Covas, Richard M. Parton, Maria Harkiolaki, Ilan Davis, Sergio Raposo Filipe, Petros Ligoxygakis

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)2480-2492.e6
JournalCell Reports
Volume27
Issue number8
DOIs
Publication statusPublished - 21 May 2019

Fingerprint

Peptidoglycan
Teichoic Acids
Gram-Positive Bacteria
Drosophila
Bacteria
Transcription
Diptera
Cell Wall
Lysine
Immunity
Infection
Cells
Diaminopimelic Acid
Pathogens
Bacilli
Bacillus subtilis
Chemical activation
peptidoglycan recognition protein

Keywords

  • B. subtilis
  • Drosophila
  • innate immunity
  • peptidoglycan
  • PGRPs
  • S. aureus
  • TagO

Cite this

Vaz, F., Kounatidis, I., Covas, G., Parton, R. M., Harkiolaki, M., Davis, I., ... Ligoxygakis, P. (2019). Accessibility to Peptidoglycan Is Important for the Recognition of Gram-Positive Bacteria in Drosophila. Cell Reports, 27(8), 2480-2492.e6. https://doi.org/10.1016/j.celrep.2019.04.103
Vaz, Filipa ; Kounatidis, Ilias ; Covas, Gonçalo ; Parton, Richard M. ; Harkiolaki, Maria ; Davis, Ilan ; Filipe, Sergio Raposo ; Ligoxygakis, Petros. / Accessibility to Peptidoglycan Is Important for the Recognition of Gram-Positive Bacteria in Drosophila. In: Cell Reports. 2019 ; Vol. 27, No. 8. pp. 2480-2492.e6.
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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.",
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Vaz, F, Kounatidis, I, Covas, G, Parton, RM, Harkiolaki, M, Davis, I, Filipe, SR & Ligoxygakis, P 2019, 'Accessibility to Peptidoglycan Is Important for the Recognition of Gram-Positive Bacteria in Drosophila' Cell Reports, vol. 27, no. 8, pp. 2480-2492.e6. https://doi.org/10.1016/j.celrep.2019.04.103

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 journalArticle

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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

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PY - 2019/5/21

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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.

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