Hemoglobin Induces Early and Robust Biofilm Development in Streptococcus pneumoniae by a Pathway That Involves comC but Not the Cognate comDE Two-Component System

Abstract

Streptococcus pneumoniae grows in biofilms during both asymptomatic colonization and infection. Pneumococcal biofilms on abiotic surfaces exhibit delayed growth and lower biomass and lack the structures seen on epithelial cells or during nasopharyngeal carriage. We show here that adding hemoglobin to the medium activated unusually early and vigorous biofilm growth in multiple S. pneumoniae serotypes grown in batch cultures on abiotic surfaces. Human blood (but not serum, heme, or iron) also stimulated biofilms, and the pore-forming pneumolysin, ply, was required for this induction. S. pneumoniae transitioning from planktonic into sessile growth in the presence of hemoglobin displayed an extensive transcriptome remodeling within 1 and 2 h. Differentially expressed genes included those involved in the metabolism of carbohydrates, nucleotides, amino acid, and lipids. The switch into adherent states also influenced the expression of several regulatory systems, including the comCDE genes. Inactivation of comC resulted in 67% reduction in biofilm formation, while the deletion of comD or comE had limited or no effect, respectively. These observations suggest a novel route for CSP-1 signaling independent of the cognate ComDE two-component system. Biofilm induction and the associated transcriptome remodeling suggest hemoglobin serves as a signal for host colonization in pneumococcus.

Oxidation of hemoglobin in the lung parenchyma facilitates the differentiation of pneumococci into encapsulated bacteria

“…We demonstrated that hemoglobin induces formation of Spn biofilms. 15,16 We next investigated if hemoglobin localizes on pneumococci. To assess this, Spn was inoculated in THY-Hb 3+ and the capsule, hemoglobin and the DNA were stained and analyzed by confocal microscopy.…”

“…We recently demonstrated that hemoglobin enhances in vitro growth of Spn strains and upregulates expression of the spxB gene and genes encoding the capsule locus. 15,16 Moreover, another recent study demonstrated that H O produced by the pneumococcus oxidizes oxy-hemoglobin (Fe 2+ ) from different mammals, including humans, to produce the non-oxygen-binding form of hemoglobin known as met-hemoglobin (Fe 3+ ). 17,18 The oxidation of hemoglobin by Spn produced potent oxidants, including labile heme 19 and a hemoglobin-derived side chain tyrosyl radical.…”

Oxidative reactions catalyzed by hydrogen peroxide produced byStreptococcus pneumoniaeand other Streptococci Cause the Release and Degradation of Heme from Hemoglobin

“…Studies of the oxidation of hemoglobin by Spn-H 2 O 2 , however, have been neglected. We recently demonstrated that the growth of planktonic Spn, and formation of pneumococcal biofilms, is enhanced by supplementing the culture medium with human hemoglobin (68, 69). Besides iron, other nutrients may become accessible to pneumococcus, since the oxidation of hemoglobin by hydrogen peroxide releases globin-derived peptides (26), but also a striking transcriptome remodeling was identified that included upregulated transcription of genes encoding transporters of glyco-conjugated molecules (68, 69).…”

Was gibt es Neues bei der Meningokokken- und Pneumokokken-Impfung?

“…Kindern < 18 Jahren in Deutschland (2011-2018) in 62,7 % der Fälle ST 3 nachgewiesen [64]. Durchbruchserkrankungen bei altersentsprechend geimpfter Kinder und begrenzter Herdenschutz bei älteren Kindern und Erwachsenen hinsichtlich ST3 in Deutschland werden diskutiert [54,[64][65][66].…”