scholarly journals Host-glycan metabolism is regulated by a species-conserved two-component system in Streptococcus pneumoniae

2020 ◽  
Vol 16 (3) ◽  
pp. e1008332
Author(s):  
Patrick Rosendahl Andreassen ◽  
Claudia Trappetti ◽  
Vikrant Minhas ◽  
Flemming Damgaard Nielsen ◽  
Kevin Pakula ◽  
...  
2010 ◽  
Vol 192 (9) ◽  
pp. 2346-2358 ◽  
Author(s):  
Alina D. Gutu ◽  
Kyle J. Wayne ◽  
Lok-To Sham ◽  
Malcolm E. Winkler

ABSTRACT The WalRK two-component system plays important roles in maintaining cell wall homeostasis and responding to antibiotic stress in low-GC Gram-positive bacteria. In the major human pathogen, Streptococcus pneumoniae, phosphorylated WalR Spn (VicR) response regulator positively controls the transcription of genes encoding the essential PcsB division protein and surface virulence factors. WalR Spn is phosphorylated by the WalK Spn (VicK) histidine kinase. Little is known about the signals sensed by WalK histidine kinases. To gain information about WalK Spn signal transduction, we performed a kinetic characterization of the WalRK Spn autophosphorylation, phosphoryltransferase, and phosphatase reactions. We were unable to purify soluble full-length WalK Spn . Consequently, these analyses were performed using two truncated versions of WalK Spn lacking its single transmembrane domain. The longer version (Δ35 amino acids) contained most of the HAMP domain and the PAS, DHp, and CA domains, whereas the shorter version (Δ195 amino acids) contained only the DHp and CA domains. The autophosphorylation kinetic parameters of Δ35 and Δ195 WalK Spn were similar [Km (ATP) ≈ 37 μM; k cat ≈ 0.10 min−1] and typical of those of other histidine kinases. The catalytic efficiency of the two versions of WalK Spn ∼P were also similar in the phosphoryltransfer reaction to full-length WalR Spn . In contrast, absence of the HAMP-PAS domains significantly diminished the phosphatase activity of WalK Spn for WalR Spn ∼P. Deletion and point mutations confirmed that optimal WalK Spn phosphatase activity depended on the PAS domain as well as residues in the DHp domain. In addition, these WalK Spn DHp domain and ΔPAS mutations led to attenuation of virulence in a murine pneumonia model.


2019 ◽  
Author(s):  
Nicolás M. Reinoso-Vizcaíno ◽  
Melina B. Cian ◽  
Paulo R. Cortes ◽  
Nadia B. Olivero ◽  
Mirelys Hernandez-Morfa ◽  
...  

AbstractThe virus-bacterial synergism implicated in secondary bacterial infections caused by Streptococcus pneumoniae following infection with epidemic or pandemic influenza A virus (IAV) is well documented. However, the molecular mechanisms behind such synergism remain largely ill-defined. In pneumocytes infected with influenza A virus, subsequent infection with S. pneumoniae leads to enhanced pneumococcal intracellular survival. The pneumococcal two-component system VisRH appears essential for such enhanced survival. Through comparative transcriptomic analysis between the ΔvisR and wt strains, a list of 179 differentially expressed genes was defined. Among those, the clpL protein chaperone gene and the psaB Mn+2 transporter gene, which are involved in the stress response, are important in enhancing S. pneumoniae survival in influenza-infected cells. The ΔvisR, ΔclpL and ΔpsaB deletion mutants display increased susceptibility to acidic and oxidative stress and no enhancement of intracellular survival in IAV-infected pneumocyte cells. These results suggest that the VisRH two-component system senses IAV-induced stress conditions and controls adaptive responses that allow survival of S. pneumoniae in IAV-infected pneumocytes.Author summaryS. pneumoniae is an inhabitant of the human nasopharynx that is capable of causing a variety of infections contributing to an estimated 1.6 million deaths each year. Many of these deaths occur as result of secondary S. pneumoniae infections following seasonal or pandemic influenza. Although S. pneumoniae is considered a typical extracellular pathogen, an intracellular survival mechanism has been more recently recognized as significant in bacterial pathogenesis. The synergistic effects between influenza A and S. pneumoniae in secondary bacterial infection are well documented; however, the effects of influenza infections on intracellular survival of S. pneumoniae are ill-defined. Here, we provide evidence that influenza infection increases S. pneumoniae intracellular survival in pneumocytes. We demonstrate that the poorly understood VisRH signal transduction system in pneumococcus controls the expression of genes involved in the stress response that S. pneumoniae needs to increase intracellular survival in influenza A-infected pneumocytes. These findings have important implications for understanding secondary bacterial pathogenesis following influenza and for the treatment of such infections in influenza-stricken patients.


2020 ◽  
Vol 16 (8) ◽  
pp. e1008761
Author(s):  
Nicolás M. Reinoso-Vizcaíno ◽  
Melina B. Cian ◽  
Paulo R. Cortes ◽  
Nadia B. Olivero ◽  
Mirelys Hernandez-Morfa ◽  
...  

2009 ◽  
Vol 46 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Xin-Ming Song ◽  
Wayne Connor ◽  
Karsten Hokamp ◽  
Lorne A. Babiuk ◽  
Andrew A. Potter

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e54320 ◽  
Author(s):  
My Trihn ◽  
Xiuchun Ge ◽  
Alleson Dobson ◽  
Todd Kitten ◽  
Cindy L. Munro ◽  
...  

2021 ◽  
Vol 89 (4) ◽  
Author(s):  
Fahmina Akhter ◽  
Edroyal Womack ◽  
Jorge E. Vidal ◽  
Yoann Le Breton ◽  
Kevin S. McIver ◽  
...  

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.


2004 ◽  
Vol 186 (16) ◽  
pp. 5258-5266 ◽  
Author(s):  
Yasser Musa Ibrahim ◽  
Alison R. Kerr ◽  
Jackie McCluskey ◽  
Tim J. Mitchell

ABSTRACT The CiaR/H two-component system is involved in regulating virulence and competence in Streptococcus pneumoniae. The system is known to regulate many genes, including that for high-temperature requirement A (HtrA). This gene has been implicated in the ability of the pneumococcus to colonize the nasopharynx of infant rats. We reported previously that deletion of the gene for HtrA made the pneumococcal strains much less virulent in mouse models, less able to grow at higher temperatures, and more sensitive to oxidative stress. In this report, we show that the growth phenotype as well as sensitivity to oxidative stress of ΔciaR mutant was very similar to that of a ΔhtrA mutant and that the expression of the HtrA protein was reduced in a ciaR-null mutant. Both the in vitro phenotype and the reduced virulence of ΔciaR mutant could be restored by increasing the expression of HtrA.


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