An uncharacterized member of the Gls24 protein superfamily is a putative sensor of essential amino acid availability in Streptococcus pneumoniae

17 p.-5 fig.-1 tab.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.This study was supported by grants BIO2017-82951-R and SAF2017-83388 from Plan Nacional de I+D+I of the Ministry of Economy, Industry and Competitiveness, and funds from the Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES) (an initiative of the Instituto de Salud Carlos III).Peer reviewe