An Uncharacterized Member of the Gls24 Protein Superfamily Is a Putative Sensor of Essential Amino Acid Availability in Streptococcus pneumoniae

Abstract

Proteins belonging to the Gls24 superfamily are involved in survival of pathogenic Gram-positive cocci under oligotrophic conditions and other types of stress, by a still unknown molecular mechanism. In Firmicutes, this superfamily includes three different valine-rich orthologal families (Gls24A, B, C) with different potential interactive partners. Whereas the Streptococcus pneumoniae Δgls24A deletion mutant experienced a general long growth delay, the Δgls24B mutant grew as the parental strain in the semisynthetic AGCH medium but failed to grow in the complex Todd-Hewitt medium. Bovine seroalbumin (BSA) was the component responsible for this phenotype. The effect of BSA on growth was concentration-dependent and was maintained when the protein was proteolyzed but not when heat-denatured, suggesting that BSA dependence was related to oligopeptide supplementation. Global transcriptional analyses of the knockout mutant revealed catabolic derepression and induction of chaperone and oligopeptide transport genes. This mutant also showed increased sensibility to cadmium and high temperature. The Δgls24B mutant behaved as a poor colonizer in the nasopharynx of mice and showed 20-fold competence impairment. Experimental data suggest that Gls24B plays a central role as a sensor of amino acid availability and its connection to sugar catabolism. This metabolic rewiring can be compensated in vitro, at the expenses of external oligopeptide supplementation, but reduce important bacteria skills prior to efficiently address systemic virulence traits. This is an example of how metabolic factors conserved in enterococci, streptococci, and staphylococci can be essential for survival in poor oligopeptide environments prior to infection progression.

A novel infective endocarditis virulence factor related to multiple functions for bacterial survival in blood was discovered inStreptococcus sanguinis

“…These data revealed that the SSA_0451 is essential for S. sanguinis to survive in nutrient-limited environments. In Streptococcus agalactiae and Streptococcus pneumoniae, similar behavior was reported in these families of proteins[18,19]. Two genes that encode putative complement system proteases are present in the genome of S. sanguinis SK36: pepO (encoding endopeptidase O) and cppA (annotated as C3-complement degrading protease; CppA)[20].…”

“…In Streptococcus agalactiae, this stress protein was necessary for bacteria to thrive in low pH and nutrient-limited environments [18]. The bile stress response, cell morphology control, and intestinal environment adaptation in Enterococcus faecium were controlled by Gls24 stress protein family proteins [32,38] The nutrition-sensing process of S. pneumoniae was significantly influenced by this protein family [19]. Our protein database search, RNA-Seq analysis (reduced and various mechanisms to escape from blood-mediated killing.…”

Media Matters, Examining Historical and Modern Streptococcus pneumoniae Growth Media and the Experiments They Affect

“…They found that when the general stress gene gls24B was knocked out, the mutant was able to grow only in the presence of BSA and growth was concentration dependent. While unable to determine what about the BSA was responsible for the phenotype, the effect was also observed using protease-treated BSA, but not with aciddigested BSA (Ferrańdiz et al, 2019). Interestingly, BSA binds fatty acids which still need to be removed and fatty acid metabolism was downregulated in the mutant (Davis and Dubos, 1947;Chen, 1967).…”

“…Another example of additives impacting phenotypes is documented by Ferrańdiz et al (2019). In this work, the authors were characterizing stress proteins in nutrient restricted conditions in semisynthetic AGCH (Adenine Glutamine Casein Hydrolysate) medium also known as modified Lacks media (Ottolenghi and Hotchkiss, 1962), in comparison to effects on nutrient rich conditions (Todd-Hewitt broth + yeast extract) (Ferrańdiz et al, 2019). They found that when the general stress gene gls24B was knocked out, the mutant was able to grow only in the presence of BSA and growth was concentration dependent.…”

Non-invasive and label-free 3D-visualization shows in vivo oligomerization of the staphylococcal alkaline shock protein 23 (Asp23)

“…Asp23 is the eponym of the poorly investigated Asp23 protein family (also termed DUF322, PF03780 or Gls24 family). Members of this protein family are exclusively present in Gram-positive bacteria 8 , where they are functionally linked to lipid metabolism (Bacillus subtilis) 9 , survival at low pH and during nutrient limitation (Streptococcus agalactiae) 10 , the bile stress response (Enterococcus faecium) 11 , cell morphology control (Enterococcus faecalis) 12 and nutrient sensing (Streptococcus pneumoniae) 13 . However, the precise mechanisms underlying these functions remain to be elucidated.…”