Peptide Ligands of AmiA, AliA, and AliB Proteins Determine Pneumococcal Phenotype

Abstract

The Ami-AliA/AliB oligopeptide permease of Streptococcus pneumoniae has been suggested to play a role in environmental sensing and colonisation of the nasopharynx by this human bacterial pathogen by binding peptides derived from bacterial neighbours of other species in the microbiota. Here, we investigated the effects of the peptide ligands of the permease’s substrate binding proteins AmiA, AliA, and AliB on pneumococcal phenotype. AmiA and AliA ligands reduced pneumococcal growth, increased biofilm production and reduced capsule size. In contrast, AliB ligand increased growth and greatly increased bacterial chain length. A decrease in transformation rate was observed in response to all three peptides. Changes in protein expression were also observed, particularly those associated with metabolism and cell wall synthesis. Understanding interspecies bacterial communication and its effect on development of colonising versus invasive phenotypes has the potential to reveal new targets to tackle and prevent pneumococcal infections.

A genome-wide atlas of antibiotic susceptibility targets and pathways to tolerance

“…5b). There is limited evidence that the ami -transporter may have (some) affinity for at least two different peptides (P1 and P2) 47-49 . These have been theorized to possibly function as signaling molecules and under certain circumstances may be generated by the bacterium itself 47-49 .…”

“…There is limited evidence that the ami -transporter may have (some) affinity for at least two different peptides (P1 and P2) 47-49 . These have been theorized to possibly function as signaling molecules and under certain circumstances may be generated by the bacterium itself 47-49 . Both peptides were synthesized and while neither peptide affects growth of the WT or knockout mutants in the absence of antibiotics (Supplementary Fig.…”

Exploring metal availability in the natural niche of Streptococcus pneumoniae to discover potential vaccine antigens

“…The adjustment of the medium to a more relevant condition concerning transition metals led to the selection of nine relevant candidate vaccine antigens based on their increased abundance in IVM-CDM versus CDM, high conservation level and putative surfaceexposure. Interestingly, the majority of these proteins are lipoproteins and function as the substrate-binding component of ATP-binding cassette (ABC)-transporter complexes: TprX is predicted to be involved in the uptake of tryptophan, MetQ is part of a methionine transporter, LivJ is involved in the uptake of leucine, isoleucine, and valine, AdcAII is part of a zinc transporter, PsaA is involved in manganese uptake, and AliA is part of an oligopeptide transporter [53][54][55][56][57][58]. The selected non-lipoproteins are SpuA, an alkaline amylopullulanase involved in glycogen degradation, PcsB, a peptidoglycan hydrolase and, PrtA, a serine protease [59][60][61].…”

“…Interestingly, AliA has been shown to be important for survival in vivo and is thought to play a role in bacterial communication by binding oligopeptides derived from other common colonizers. Peptide uptake by pneumococci via AliA has shown to influence the behavior of the bacterium in vitro, including reduced growth, reduced capsule thickness, and increased biofilm formation [11,57,58,77]. It is, therefore, tempting to speculate that in vivo anti-AliA antibodies could hamper the uptake of oligopeptides by AliA and consequently affect pneumococcal persistence in the host.…”

Peptide Occurring in Enterobacteriaceae Triggers Streptococcus pneumoniae Cell Death

“…They have two genes, aliB- like ORF 1 and aliB- like ORF 2, in place of the capsule genes, that are homologs of the gene encoding AliB substrate binding protein, found in all pneumococci (Hathaway et al, 2004). Previously, we have proposed a mechanism of interspecies communication consisting of specific binding of peptides derived from other bacterial species found in the nasopharyngeal microbiota via such substrate binding proteins, triggering changes in pneumococcal phenotype (Hathaway et al, 2014; Nasher et al, 2018a,b,c). AliB-like ORF 1 binds specifically to peptide SETTFGRDFN, matching 50S ribosomal subunit protein L4 of Enterobacteriaceae, promoting competence for genetic transformation in the presence of CSP (Hathaway et al, 2014).…”