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Function of BriC peptide in the pneumococcal competence and virulence portfolio

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posted on 11.10.2018, 00:00 by Surya AggarwalSurya Aggarwal, Rory EutseyRory Eutsey, Jacob West-Roberts, Arnau Domenech, Wenjie XueWenjie Xue, Iman Tajer Abdullah, Aaron MitchellAaron Mitchell, Jan-Willem Veening, Hasan Yesilkaya, Natalia HillerNatalia 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 briCdoes 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, briCpromotes 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 briCpromoter. 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. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article published with support from the Carnegie Mellon University Article Processing Charge (APC) Fund.

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Publisher Statement

This is the published PDF version of, “Aggarwal SD, Eutsey R, West-Roberts J, Domenech A, Xu W, et al. (2018) Function of BriC peptide in the pneumococcal competence and virulence portfolio. PLOS Pathogens 14(10): e1007328. https://doi.org/10.1371/journal.ppat.1007328.”

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11/10/2018

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