Abstract
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.
Highlights
Bacteria form sessile communities termed biofilms, where they interact with each other to engage in collaborative and/or competitive behaviors [1]
Pneumococcal biofilms occur in chronic otitis media, chronic rhinosinusitis, and nasopharyngeal colonization
We have identified BriC, a previously uncharacterized peptide that serves as a bridge between the competence pathway and biofilm development
Summary
Bacteria form sessile communities termed biofilms, where they interact with each other to engage in collaborative and/or competitive behaviors [1]. In Streptococcus pneumoniae (pneumococcus), these cell-cell interactions are commonly mediated by secreted peptides that interact with both producing and neighboring cells of the same species, and induce changes in gene regulation that result in altered phenotypes [2] These dynamic pneumococcal biofilms occur in chronic otitis media, chronic rhinosinusitis and nasopharyngeal colonization [3,4,5,6,7,8]. Bacterial cells released from nasopharyngeal biofilms can seed pneumococcal transmission between individuals by being incorporated into nasal shedding. These cells can disseminate to tissues causing mild to severe diseases, such as otitis media, pneumonia, and sepsis [10]. Biofilms are an important component of pneumococcal epidemiology in transmission, maintenance of asymptomatic colonization, and development of disease
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