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Function of BriC peptide in the pneumococcal competence and virulence portfolio.

journal contribution
posted on 06.02.2019, 11:39 by SD Aggarwal, R Eutsey, J West-Roberts, A Domenech, W Xu, IT Abdullah, AP Mitchell, J-W Veening, H Yesilkaya, NL Hiller
Streptococcus pneumoniae (pneumococcus) is an opportunistic pathogen that causes otitis media, sinusitis, pneumonia, meningitis and sepsis. The progression to this pathogenic lifestyle is preceded by asymptomatic colonization of the nasopharynx. This colonization is associated with biofilm formation; the competence pathway influences the structure and stability of biofilms. However, the molecules that link the competence pathway to biofilm formation are unknown. Here, we describe a new competence-induced gene, called briC, and demonstrate that its product promotes biofilm development and stimulates colonization in a murine model. We show that expression of briC is induced by the master regulator of competence, ComE. Whereas briC does not substantially influence early biofilm development on abiotic surfaces, it significantly impacts later stages of biofilm development. Specifically, briC expression leads to increases in biofilm biomass and thickness at 72h. Consistent with the role of biofilms in colonization, briC promotes nasopharyngeal colonization in the murine model. The function of BriC appears to be conserved across pneumococci, as comparative genomics reveal that briC is widespread across isolates. Surprisingly, many isolates, including strains from clinically important PMEN1 and PMEN14 lineages, which are widely associated with colonization, encode a long briC promoter. This long form captures an instance of genomic plasticity and functions as a competence-independent expression enhancer that may serve as a precocious point of entry into this otherwise competence-regulated pathway. Moreover, overexpression of briC by the long promoter fully rescues the comE-deletion induced biofilm defect in vitro, and partially in vivo. These findings indicate that BriC may bypass the influence of competence in biofilm development and that such a pathway may be active in a subset of pneumococcal lineages. In conclusion, BriC is a part of the complex molecular network that connects signaling of the competence pathway to biofilm development and colonization.

Funding

This work was supported by NIH grant R00-DC-011322 to NLH, Stupakoff Scientific Achievement Award to SDA, as well as support from the Department of Biological Sciences at Carnegie Mellon University.

History

Citation

PLoS Pathogens, 2018, 14 (10), pp. e1007328-?

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

PLoS Pathogens

Publisher

Public Library of Science

eissn

1553-7374

Acceptance date

10/09/2018

Copyright date

2018

Available date

06/02/2019

Publisher version

https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007328

Language

en

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