Cationic bactericidal peptide 1018 does not specifically target the stringent response alarmone (p)ppGpp
Andresen, Liis ; Tenson, Tanel and Hauryliuk, Vasili LU
(2016)
In Scientific Reports
6.
- Abstract
The bacterial stringent response is a key regulator of bacterial virulence, biofilm formation and antibiotic tolerance, and is a promising target for the development of new antibacterial compounds. The intracellular nucleotide (p)ppGpp acts as a messenger orchestrating the stringent response. A synthetic peptide 1018 was recently proposed to specifically disrupt biofilms by inhibiting the stringent response via direct interaction with (p)ppGpp (de la Fuente-Núñez et al. (2014) PLoS Pathogens). We have interrogated the specificity of the proposed molecular mechanism. When inhibition of Pseudomonas aeruginosa planktonic and biofilm growth is tested simultaneously in the same assay, peptides 1018 and the control peptide 8101 generated by... (More)
The bacterial stringent response is a key regulator of bacterial virulence, biofilm formation and antibiotic tolerance, and is a promising target for the development of new antibacterial compounds. The intracellular nucleotide (p)ppGpp acts as a messenger orchestrating the stringent response. A synthetic peptide 1018 was recently proposed to specifically disrupt biofilms by inhibiting the stringent response via direct interaction with (p)ppGpp (de la Fuente-Núñez et al. (2014) PLoS Pathogens). We have interrogated the specificity of the proposed molecular mechanism. When inhibition of Pseudomonas aeruginosa planktonic and biofilm growth is tested simultaneously in the same assay, peptides 1018 and the control peptide 8101 generated by an inversion of the amino acid sequence of 1018 are equally potent, and, importantly, do not display a preferential activity against biofilm. 1018 inhibits planktonic growth of Escherichia coli equally efficiently either when the alleged target, (p)ppGpp, is essential (MOPS media lacking amino acid L-valine), or dispensable for growth (MOPS media supplemented with L-valine). Genetic disruption of the genes relA and spoT responsible for (p)ppGpp synthesis moderately sensitizes - rather than protects - E. coli to 1018. We suggest that the antimicrobial activity of 1018 does not rely on specific recognition of the stringent response messenger (p)ppGpp.
(Less)
- author
- Andresen, Liis
; Tenson, Tanel
and Hauryliuk, Vasili
LU
- publishing date
- 2016-11-07
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 6
- article number
- 36549
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:84994526175
- pmid:27819280
- ISSN
- 2045-2322
- DOI
- 10.1038/srep36549
- language
- English
- LU publication?
- no
- additional info
- Funding Information: This work was supported by the grant IUT2-22 from the Estonian Research Council (TT); European Regional Development Fund through the Centre of Excellence for Molecular Cell Technology (VH and TT); Estonian Science Foundation (PUT37 to VH); Ume? University, the Swedish Research council (Vetenskapsr?det; grant 2013-4680) and the Kempe and Ragnar S?derberg foundations (VH). The work was performed as part of the Ume? Centre for Microbial Research (UCMR) Linnaeus Program supported by Ume? University and the Swedish Research Council (349-2007-8673). Publisher Copyright: © The Author(s) 2016. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.
- id
- 9bfdb4ac-aae5-455b-a1a2-b4fbc37f878d
- date added to LUP
- 2021-09-24 20:41:35
- date last changed
- 2024-06-29 18:20:27
@article{9bfdb4ac-aae5-455b-a1a2-b4fbc37f878d,
abstract = {{<p>The bacterial stringent response is a key regulator of bacterial virulence, biofilm formation and antibiotic tolerance, and is a promising target for the development of new antibacterial compounds. The intracellular nucleotide (p)ppGpp acts as a messenger orchestrating the stringent response. A synthetic peptide 1018 was recently proposed to specifically disrupt biofilms by inhibiting the stringent response via direct interaction with (p)ppGpp (de la Fuente-Núñez et al. (2014) PLoS Pathogens). We have interrogated the specificity of the proposed molecular mechanism. When inhibition of Pseudomonas aeruginosa planktonic and biofilm growth is tested simultaneously in the same assay, peptides 1018 and the control peptide 8101 generated by an inversion of the amino acid sequence of 1018 are equally potent, and, importantly, do not display a preferential activity against biofilm. 1018 inhibits planktonic growth of Escherichia coli equally efficiently either when the alleged target, (p)ppGpp, is essential (MOPS media lacking amino acid L-valine), or dispensable for growth (MOPS media supplemented with L-valine). Genetic disruption of the genes relA and spoT responsible for (p)ppGpp synthesis moderately sensitizes - rather than protects - E. coli to 1018. We suggest that the antimicrobial activity of 1018 does not rely on specific recognition of the stringent response messenger (p)ppGpp.</p>}},
author = {{Andresen, Liis and Tenson, Tanel and Hauryliuk, Vasili}},
issn = {{2045-2322}},
language = {{eng}},
month = {{11}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Cationic bactericidal peptide 1018 does not specifically target the stringent response alarmone (p)ppGpp}},
url = {{http://dx.doi.org/10.1038/srep36549}},
doi = {{10.1038/srep36549}},
volume = {{6}},
year = {{2016}},
}