Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Elsevier Science full text link Elsevier Science Free PMC article
Full text links

Actions

Share

.2019 Aug:89:102987.
doi: 10.1016/j.bioorg.2019.102987. Epub 2019 May 18.

Exploring the competence stimulating peptide (CSP) N-terminal requirements for effective ComD receptor activation in group1 Streptococcus pneumoniae

Affiliations

Exploring the competence stimulating peptide (CSP) N-terminal requirements for effective ComD receptor activation in group1 Streptococcus pneumoniae

Yifang Yang et al. Bioorg Chem.2019 Aug.

Abstract

The competence stimulating peptide (CSP) plays a key role in the regulation of pneumococcal quorum sensing (QS), a communication system that is critical to the infectivity of pneumococci. CSP functions through binding and activating a transmembrane receptor, ComD. Molecules that can modulate pneumococcal QS through intercepting CSP:ComD interaction may serve as new generation of antibacterial agents to treat pneumococcal infections. In this work, we systematically modified the N-terminus of CSP1, a region that is essential to ComD activation, to identify detailed structural features of the N-terminus that are responsible for its function. Our results revealed structural features that are optimal to achieve receptor activation and structure-activity trends that improve our understanding of CSP:ComD interaction, all of which will contribute to the design of novel pneumococcal QS modulators with higher potency and improved pharmacological properties.

Keywords: Competence stimulating peptide; Quorum sensing; Streptococcus pneumoniae; Structure-activity relationship.

Copyright © 2019 Elsevier Inc. All rights reserved.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
S. pneumoniae CSP-mediated QS circuit. CSP is made from a propeptide, Com C, which is encoded by thecom C gene. An ABC transporter, Com AB, then cleaves the propeptide and exports the mature CSP out of the cell. As the population of the bacteria grows, the concentration of CSP increases. Once the concentration of CSP reaches a threshold, CSP can effectively bind and activate a transmembrane histidine kinase receptor, Com D. On activation, Com D activates its response regulator, Com E, through phosphorylation. Activated Com E can trigger the transcription of numerous genes includingcom X, which is responsible for the induction of competence. The sequence of CSP1 is shown.
Figure 2.
Figure 2.
Structure and bioactivity of the first set of CSP1 analogs.a The concentrations in black are EC50 values determined by testing peptides over a range of concentrations.b The concentrations in red are IC50 values determined by testing peptides over a range of concentrations in the presence of CSP1.c The percentage in red is the average of ComD1 activation by CSP1 in the presence of 10 μM inhibitor.d The percentage in black is the average of ComD1 activation by 10 μM of the CSP1 analog.e Dap stands for 2,3-Diaminopropionic acid.f EC50/IC50 values taken from ref 23. See the Supporting Information for detail of reporter strains, methods, and plots of agonism and antagonism dose response curves. All assays performed in triplicate.
Figure 3.
Figure 3.
Structure and bioactivity of the second set of CSP1 analogs.a The concentrations in black are EC50 values determined by testing peptides over a range of concentrations.b The percentage in black is the average of ComD1 activation by 10 μM of the CSP1 analog.c The concentrations in red are IC50 values determined by testing peptides over a range of concentrations in the presence of CSP1.d The percentage in red is the average of ComD1 activation by CSP1 in the presence of 10 μM inhibitor.e Aad stands for α-Aminoadipic acid.f Dab stands for 2,4-Diaminobutyric acid.g Orn stands for Ornithine. See the Supporting Information for detail of reporter strains, methods, and plots of agonism and antagonism dose response curves. All assays performed in triplicate.
Figure 4.
Figure 4.
Structure and bioactivity of the third set of CSP1 analogs.a The percentage in black is the average of ComD1 activation by 10 μM of the CSP1 analog.b The percentage in red is the average of ComD1 activation by CSP1 in the presence of 10 μM inhibitor.c The concentrations in black are EC50 values determined by testing peptides over a range of concentrations.d The concentrations in red are IC50 values determined by testing peptides over a range of concentrations in the presence of CSP1. e Succ stands for succinyl group. See the Supporting Information for detail of reporter strains, methods, and plots of agonism and antagonism dose response curves. All assays performed in triplicate.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mehr S; Wood N, Streptococcus pneumoniae--a review of carriage, infection, serotype replacement and vaccination. Paediatr. Respir. Rev 2012, 13 (4), 258–64. - PubMed
    1. Walker CLF; Rudan I; Liu L; Nair H; Theodoratou E; Bhutta ZA; O’Brien KL;Campbell H; Black RE, Global burden of childhood pneumonia and diarrhoea. Lancet 2013, 381 (9875), 1405–1416. - PMC - PubMed
    1. Linares J; Ardanuy C; Pallares R; Fenoll A, Changes in antimicrobial resistance, serotypes and genotypes in Streptococcus pneumoniae over a 30-year period. Clin. Microbiol. Infect 2010, 16 (5), 402–10. - PubMed
    1. LaSarre B; Federle MJ, Exploiting quorum sensing to confuse bacterial pathogens. Microbiol. Mol. Biol. Rev 2013, 77 (1), 73–111. - PMC - PubMed
    1. Brannon JR; Hadjifrangiskou M, The arsenal of pathogens and antivirulence therapeutic strategies for disarming them. Drug Des. Devel. Ther 2016, 10, 1795–806. - PMC - PubMed

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full text links
Elsevier Science full text link Elsevier Science Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp