Impact of the glpQ2 Gene on Virulence in a Streptococcus pneumoniae Serotype 19A Sequence Type 320 Strain

Abstract

dGlycerophosphodiester phosphodiesterase (GlpQ) metabolizes glycerophosphorylcholine from the lung epithelium to produce free choline, which is transformed into phosphorylcholine and presented on the surfaces of many respiratory pathogens. Two orthologs of glpQ genes are found in Streptococcus pneumoniae: glpQ, with a membrane motif, is widespread in pneumococci, whereas glpQ2, which shares high similarity with glpQ in Haemophilus influenzae and Mycoplasma pneumoniae, is present only in S. pneumoniae serotype 3, 6B, 19A, and 19F strains. Recently, serotype 19A has emerged as an epidemiological etiology associated with invasive pneumococcal diseases. Thus, we investigated the pathophysiological role of glpQ2 in a serotype 19A sequence type 320 (19AST320) strain, which was the prevalent sequence type in 19A associated with severe pneumonia and invasive pneumococcal disease in pediatric patients. Mutations in glpQ2 reduced phosphorylcholine expression and the anchorage of cholinebinding proteins to the pneumococcal surface during the exponential phase, where the mutants exhibited reduced autolysis and lower natural transformation abilities than the parent strain. The deletion of glpQ2 also decreased the adherence and cytotoxicity to human lung epithelial cell lines, whereas these functions were indistinguishable from those of the wild type in complementation strains. In a murine respiratory tract infection model, glpQ2 was important for nasopharynx and lung colonization. Furthermore, infection with a glpQ2 mutant decreased the severity of pneumonia compared with the parent strain, and glpQ2 gene complementation restored the inflammation level. Therefore, glpQ2 enhances surface phosphorylcholine expression in S. pneumoniae 19AST320 during the exponential phase, which contributes to the severity of pneumonia by promoting adherence and host cell cytotoxicity. P hosphorylcholine (ChoP) is a unique feature of many respiratory bacterial species. In the cell wall of pneumococci, ChoP is a component of lipoteichoic acid and teichoic acid that anchors various choline-binding proteins (CBPs) via the choline-binding domain on the pneumococcal surface (1). These CBPs regulate autolysis and the natural transformation of Streptococcus pneumoniae (2), as well as promoting the internalization of pneumococci into pharyngeal epithelial cells to escape phagocytes (3-6).The structure of ChoP resembles that of the platelet-activating factor (PAF), and thus, ChoP on S. pneumoniae can interact directly with the host PAF receptor (7) and allow S. pneumoniae to transit the epithelial and endothelial layers during invasion (8). The conjugation between ChoP and the PAF receptor is important for pneumococcal sequestration during immune clearance and systemic dissemination, since mice deficient in PAF receptor or treated with PAF receptor antagonist abolish pneumococcal pneumonia progression to cause sepsis and meningitis (9).The presentation of ChoP on the bacterial surface requires an available choline source in the environment (10, 11). Fre...

Proteomics insights into the Burkholderia cenocepacia phosphorus stress response

“…GlpQ is required for pathogenicity against HeLa cells due to its indirect role in hydrogen peroxide formation (Schmidl et al ., 2011). A similar observation was found in Streptococcus pneumoniae whereby cytotoxicity was compromised in GlpQ mutants infecting human epithelial cells (Chuang et al ., 2015). Ppk was shown in Burkholderia pseudomallei to be important for swarming and swimming motility, as well as biofilm formation (Tunpiboonsak et al ., 2010).…”

Identification of extracellular glycerophosphodiesterases in Pseudomonas and their role in soil organic phosphorus remineralisation

“…coli (identity 36.78%, e-value, 2.0 e-54). PSTAA_4169, hereafter termed glpQI , encodes a protein (GlpQI) containing all the conserved residues associated with characterised GDPDs 29 (Fig. S1 ).…”

“…stutzeri DSM4166 was isolated from the rhizosphere of yellow indiangrass ( Sorghum nutans ) 33 . Like other GlpQ-harbouring bacteria, both of these Pseudomonas strains form close associations with eukaryotic organisms suggesting that the ability to degrade phospholipid headgroups confers an ecological advantage in these environments 27 , 29 , 30 , 37 . Interestingly, in P .…”

“…Therefore, the release of Pi from glycerolphosphodiesters is a multi-step process with the final step performed by ALPs. GDPDs, namely GlpQ, produced by phylogenetically distinct bacteria such as Escherichia , Bacillus , Streptococcus , Mycoplasma and Streptomyces are often required for establishing various relationships (pathogenic or mutualistic) between bacteria and their recipient hosts 21 , 27 , 29 , 30 . A periplasmic GlpQ was first characterised in E .…”

Enterococcal Bacteriophage: A Survey of the Tail Associated Lysin Landscape

“…The second DA harbours a GDPD domain and a predicted membrane domain (PF10110.9) (Fig. 8A) homologues of which have found in Streptococcus bacterial genomes (Chuang et al, 2015). The third DA contains the GDPD domain at the C-terminus with a predicted baseplate upper protein (BppU) located at the N-terminal end indicating that this is likely a multifunctional baseplate-lyase protein in phage 9183.…”