Biology subjects

Dawid, S.

Publications and source records attributed to Dawid, S..

3 recordsLinked to original sources

bioRxiv2024

The pneumococcal bacteriocin streptococcin B is produced as part of the early competence cascade and promotes intraspecies competition.

Streptococcus pneumoniae is an important human pathogen that normally resides in the human nasopharynx. Competence mediated bacteriocin expression by S pneumoniae plays a major role in both the establishment and persistence of colonization on this polymicrobial surface. Over 20 distinct bacteriocin loci have been identified in pneumococcal genomes, but only a small number have been characterized phenotypically. In this work, we demonstrate that 3/4th of S. pneumoniae strains contain a highly conserved scb locus that encodes an active lactococcin 972-like bacteriocin called Streptococcin B. In these backgrounds, the scbABC locus is part of the early competence cascade due to a ComE binding site in the promoter region. Streptococcin B producing strains target both members of the population that have failed to activate competence and the 25% of the population that carry a naturally occurring deletion of the ComE binding site and the functional bacteriocin gene. The ComR-type regulator found directly upstream of the scb locus in S. pneumoniae strains can activate scb expression independent of the presence of the ComE binding site but only when stimulated by a peptide that is encoded in the scb locus of S. pseudopneumoniae, a closely related bacterium which also inhabits the human nasopharynx. Given the co-regulation with competence and the phenotypic confirmation of activity, Streptococcin B represents a previously unrecognized fratricide effector that gives producing strains an additional advantage over the naturally occurring deleted strains during colonization. ImportanceStreptococcus pneumoniae is a common cause of pneumonia, meningitis, sinusitis and otitis media. In order to successfully colonize humans, a pre-requisite to the development of invasive disease, S. pneumoniae must compete with other bacterial inhabitants of the nasal surface for space and nutrients. Bacteriocins are small antimicrobial peptides produced by bacteria that typically target neighboring bacteria by disruption of the cell surface. S. pnuemoniae encodes a large number of potential bacteriocin, but, for most, their role in competitive interactions has not been defined. This work demonstrates that isolates that produce the bacteriocin Streptococcin B have an advantage over non producers. These observations contribute to our understanding of the competitive interactions that precede development of S. pneumoniae disease.

microbiology↗

bioRxiv2022

The outer surface protease, SepM, is required for blp locus activation in three of the four most common pherotypes of Streptococcus pneumoniae.

Streptococcus pneumoniae (pneumococcus) is an important human pathogen that primarily resides in the nasopharynx. To persist in this polymicrobial environment, pneumococcus must compete with other members of the bacterial community. Competition is mediated in part by the action of the blp locus which encodes a variable array of bacteriocins and their associated immunity proteins. The locus is controlled by a two-component regulatory system that senses the extracellular concentration of the peptide pheromone, BlpC. There are four major pherotypes of BlpC that can be found in most pneumococcal genomes. Here, we show that the protease, SepM, is required for activation of three of the four major pherotypes. The only SepM independent BlpC type is 9AA shorter than the SepM-dependent peptides, consistent with a cleavage event at the C-terminal end. The processing event occurs following secretion and removal of the C terminal region is required for binding to the histidine kinase receptor. Synthetic truncated peptides or full-length peptides pre-incubated with SepM-expressing bacteria can upregulate the blp locus independent of SepM. We show that SepM-independent peptides accumulate in the supernatant of secreting cells at low levels suggesting a role for the tail in peptide secretion, stability or solubility and demonstrating a significant tradeoff for SepM-independence. ImportanceStreptococcus pneumoniae is an important cause of disease in humans that occurs when the bacteria in the nasopharynx bypasses host defenses to invade deeper tissues. Colonization fitness thus represents an important initial step in pathogenesis. S. pneumoniae produces antimicrobial peptides called bacteriocins which provide a competitive advantage over neighboring bacteria in the nasopharynx. The blp locus encodes a variable array of bacteriocins that participate in competition. Here, we demonstrate that activation of the blp locus requires a surface protease that activates the blp signal peptide. There are naturally occurring signal peptides that do not require cleavage, but these are characterized by poor secretion. We describe an additional, previously unappreciated activation step in the control of bacteriocin production in S. pneumoniae.

microbiology↗

bioRxiv2019

Molecular Determinants of Substrate Selectivity of a Pneumococcal Rgg-regulated Peptidase-Containing ABC Transporter.

Peptidase-containing ABC transporters (PCATs) are a widely distributed family of transporters which secrete double-glycine (GG) peptides. In the opportunistic pathogen Streptococcus pneumoniae (pneumococcus), the PCATs ComAB and BlpAB have been shown to secrete quorum-sensing pheromones and bacteriocins related to the competence and pneumocin pathways. Here, we describe another pneumococcal PCAT, RtgAB, encoded by the rtg locus and found intact in 17% of strains. The Rgg/SHP-like quorum sensing system RtgR/S, which uses a peptide pheromone with a distinctive Trp-X-Trp motif, regulates expression of the rtg locus and provides a competitive fitness advantage in a mouse model of nasopharyngeal colonization. RtgAB secretes a set of co-regulated rtg GG peptides. ComAB and BlpAB, which share a substrate pool with each other, do not secrete the rtg GG peptides. Similarly, RtgAB does not efficiently secrete ComAB/BlpAB substrates. We examined the molecular determinants of substrate selectivity between ComAB, BlpAB, and RtgAB and found that the GG peptide signal sequences contain all the information necessary to direct secretion through specific transporters. Secretion through ComAB and BlpAB depends largely on the identity of four conserved hydrophobic signal sequence residues previously implicated in substrate recognition by PCATs. In contrast, a motif situated at the N-terminal end of the signal sequence, found only in rtg GG peptides, directs secretion through RtgAB. These findings illustrate the complexity in predicting substrate-PCAT pairings by demonstrating specificity that is not dictated solely by signal sequence residues previously implicated in substrate recognition.\n\nImportanceThe export of peptides from the cell is a fundamental process carried out by all bacteria. One method of bacterial peptide export relies on a family of transporters called peptidase-containing ABC transporters (PCATs). PCATs export so-called GG peptides which carry out diverse functions, including cell-to-cell communication and inter-bacterial competition. In this work, we describe a PCAT-encoding genetic locus, rtg, in the pathogen Streptococcus pneumoniae (pneumococcus). The rtg locus is linked to increased competitive fitness advantage in a mouse model of nasopharyngeal colonization. We also describe how the rtg PCAT preferentially secretes a set of co-regulated GG peptides but not GG peptides secreted by other pneumococcal PCATs. These findings illuminate a relatively understudied part of PCAT biology: how these transporters discriminate between different subsets of GG peptides. Ultimately, expanding our knowledge of PCATs will advance our understanding of the many microbial processes dependent on these transporters.

microbiology↗