A Quorum-Sensing System That Regulates Streptococcus pneumoniae Biofilm Formation and Surface Polysaccharide Production

Junges, Roger; Salvadori, Gabriela; Shekhar, Sudhanshu; Åmdal, Heidi Aarø; Periselneris, Jimstan; Chen, Tsute; Brown, Jeremy S.; Petersen, Fernanda Cristina

doi:10.1128/msphere.00324-17

Cited by 45 publications

(75 citation statements)

References 77 publications

(124 reference statements)

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“…A recent study characterized a quorum-sensing Rgg/SHP system in S. pneumoniae that increases surface polysaccharide synthesis by upregulation of a site distinct from the original capsule locus (28). Considering the genetic similarities between the pathogenic S. pneumoniae and oral streptococci from the mitis group, this study addressed whether other such systems could be identified in these closely related oral species as well.…”

Section: Screening Of Rgg/shp Cell-to-cell Communication Systems In Omentioning

confidence: 99%

“…The search was performed using the expanded Human Oral Microbiome Database (HOMD) (32), a curated and comprehensive database on the bacterial species present in the human aerodigestive tract. Entries of species belonging to the mitis group of streptococci were included in the search, with the only exclusion being S. pneumoniae since it was recently described (28). In total, we examined 15 strains of S. mitis, 1 strain of S. gordonii, 9 strains of S. oralis, 13 strains of S. sanguinis, and 7 strains of S. parasanguinis.…”

Section: Screening Of Rgg/shp Cell-to-cell Communication Systems In Omentioning

confidence: 99%

“…An SHP concentration of 4.5 M was chosen based on studies with other streptococcal species indicating that this concentration would saturate the system. Pellet collection for RNA extraction was performed at 2 h due to previous reports indicating high activation of the pheromone system at this time point (28). In addition, since we have been unable to find a chemically defined peptide-free medium that works well for S. mitis, we opted to test rich and semidefined media for activation of the system.…”

Section: Screening Of Rgg/shp Cell-to-cell Communication Systems In Omentioning

confidence: 99%

“…Moreover, in the pyogenic, salivarius, bovis, and mutans groups of streptococci, natural competence for transformation is regulated by the ComRS system, which belongs to the Rgg/SHP family (26). In the mitis group of streptococci, a TprA/PhrA quorum-sensing system that regulates a lantibiotic biosynthesis gene cluster (27) and an Rgg/SHP system that regulates surface polysaccharide expression (28) have both been recently reported in S. pneumoniae. While interspecies cross-communication has been detected in some of these systems (29)(30)(31), it is important to note that the stringency of SHP recognition by Rgg proteins across species is variable and, in general, a high specificity of the Rgg and SHP interaction is expected.…”

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confidence: 99%

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Characterization of a Signaling System in Streptococcus mitis That Mediates Interspecies Communication with Streptococcus pneumoniae

Junges

Sturød

Salvadori

et al. 2019

Appl Environ Microbiol

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Streptococcus mitis is found in the oral cavity and nasopharynx and forms a significant portion of the human microbiome. In this study, in silico analyses indicated the presence of an Rgg regulator and short hydrophobic peptide (Rgg/SHP) cell-to-cell communication system in S. mitis. Although Rgg presented greater similarity to a repressor in Streptococcus pyogenes, autoinducing assays and genetic mutation analysis revealed that in S. mitis Rgg acts as an activator. Transcriptome analysis showed that in addition to shp, the system regulates two other downstream genes, comprising a segment of a putative lantibiotic gene cluster that is in a conjugative element locus in different members of the mitis group. Close comparison to a similar lantibiotic gene cluster in Streptococcus pneumoniae indicated that S. mitis lacked the full set of genes. Despite the potential of SHP to trigger a futile cycle of autoinduction, growth was not significantly affected for the rgg mutant under normal or antibiotic stress conditions. The S. mitis SHP was, however, fully functional in promoting cross-species communication and increasing S. pneumoniae surface polysaccharide production, which in this species is regulated by Rgg/SHP. The activity of SHPs produced by both species was detected in cocultures using a S. mitis reporter strain. In competitive assays, a slight advantage was observed for the rgg mutants. We conclude that the Rgg/SHP system in S. mitis regulates the expression of its own shp and activates an Rgg/SHP system in S. pneumoniae that regulates surface polysaccharide synthesis. Fundamentally, cross-communication of such systems may have a role during multispecies interactions. IMPORTANCE Bacteria secrete signal molecules into the environment which are sensed by other cells when the density reaches a certain threshold. In this study, we describe a communication system in Streptococcus mitis, a commensal species from the oral cavity, which we also found in several species and strains of streptococci from the mitis group. Further, we show that this system can promote cross-communication with S. pneumoniae, a closely related major human pathogen. Importantly, we show that this cross-communication can take place during coculture. While the genes regulated in S. mitis are likely part of a futile cycle of activation, the target genes in S. pneumoniae are potentially involved in virulence. The understanding of such complex communication networks can provide important insights into the dynamics of bacterial communities.

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Section: Screening Of Rgg/shp Cell-to-cell Communication Systems In Omentioning

confidence: 99%

Section: Screening Of Rgg/shp Cell-to-cell Communication Systems In Omentioning

confidence: 99%

Section: Screening Of Rgg/shp Cell-to-cell Communication Systems In Omentioning

confidence: 99%

mentioning

confidence: 99%

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Characterization of a Signaling System in Streptococcus mitis That Mediates Interspecies Communication with Streptococcus pneumoniae

Junges

Sturød

Salvadori

et al. 2019

Appl Environ Microbiol

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“…The Ami oligopeptide importer then internalizes the pheromones back into the cell, where they bind to and modulate the activity of Rgg-family regulators (12). Besides PCATs and bacteriocin production, Rgg/SHP systems have been found to regulate diverse processes such as carbohydrate utilization (15), tissue invasion (13, 16), capsule production (16, 17), and biofilm formation (17, 18). A related group of Rgg regulators, the ComRs, are associated with SHP-like pheromones called ComS or XIP (SigX-inducing peptide) and control competence activation in some streptococcal species (19, 20).…”

Section: Introductionmentioning

confidence: 99%

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

Wang¹,

Medlin

Nguyen

et al. 2019

Preprint

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word count: (abstract/importance: 235/145) 14 Text word count: 4911 15 32 Abstract 33 34 Peptidase-containing ABC transporters (PCATs) are a widely distributed family of 35 transporters which secrete double-glycine (GG) peptides. In the opportunistic pathogen 36 Streptococcus pneumoniae (pneumococcus), the PCATs ComAB and BlpAB have been 37 shown to secrete quorum-sensing pheromones and bacteriocins related to the 38 competence and pneumocin pathways. Here, we describe another pneumococcal 39 PCAT, RtgAB, encoded by the rtg locus and found intact in 17% of strains. The 40 Rgg/SHP-like quorum sensing system RtgR/S, which uses a peptide pheromone with a 41 distinctive Trp-X-Trp motif, regulates expression of the rtg locus and provides a 42 competitive fitness advantage in a mouse model of nasopharyngeal colonization. RtgAB 43 secretes a set of co-regulated rtg GG peptides. ComAB and BlpAB, which share a 44 substrate pool with each other, do not secrete the rtg GG peptides. Similarly, RtgAB 45 does not efficiently secrete ComAB/BlpAB substrates. We examined the molecular 46 determinants of substrate selectivity between ComAB, BlpAB, and RtgAB and found 47 that the GG peptide signal sequences contain all the information necessary to direct 48 secretion through specific transporters. Secretion through ComAB and BlpAB depends 49 largely on the identity of four conserved hydrophobic signal sequence residues 50 previously implicated in substrate recognition by PCATs. In contrast, a motif situated at 51 the N-terminal end of the signal sequence, found only in rtg GG peptides, directs 52 secretion through RtgAB. These findings illustrate the complexity in predicting 53 substrate-PCAT pairings by demonstrating specificity that is not dictated solely by signal 54 sequence residues previously implicated in substrate recognition. 55 56 Importance 57 58The export of peptides from the cell is a fundamental process carried out by all 59 bacteria. One method of bacterial peptide export relies on a family of transporters called 60 peptidase-containing ABC transporters (PCATs). PCATs export so-called GG peptides 61 which carry out diverse functions, including cell-to-cell communication and inter-62 bacterial competition. In this work, we describe a PCAT-encoding genetic locus, rtg, in 63 the pathogen Streptococcus pneumoniae (pneumococcus). The rtg locus is linked to 64 increased competitive fitness advantage in a mouse model of nasopharyngeal 65 colonization. We also describe how the rtg PCAT preferentially secretes a set of co-66 regulated GG peptides but not GG peptides secreted by other pneumococcal PCATs. 67These findings illuminate a relatively understudied part of PCAT biology: how these 68 transporters discriminate between different subsets of GG peptides.

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Targeting peptide‐based quorum sensing systems for the treatment of gram‐positive bacterial infections

Milly

Tal‐Gan

2022

Peptide Science

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Bacteria utilize a cell density-dependent communication system called quorum sensing (QS) to coordinate group behaviors. In Gram-positive bacteria, QS involves the production of and response to auto-inducing peptide (AIP) signaling molecules to modulate group phenotypes, including pathogenicity. As such, this bacterial communication system has been identified as a potential therapeutic target against bacterial infections. More specifically, developing synthetic modulators derived from the native peptide signal paves a new way to selectively block the pathogenic behaviors associated with this signaling system. Moreover, rational design and development of potent synthetic peptide modulators allows in depth understanding of the molecular mechanisms that drive QS circuits in diverse bacterial species. Overall, studies aimed at understanding the role of QS in microbial social behavior could result in the accumulation of significant knowledge of microbial interactions, and consequently lead to the development of alternative therapeutic agents to treat bacterial infectivity. In this review, we discuss recent advances in the development of peptide-based modulators to target QS systems in Gram-positive pathogens, with a focus on evaluating the therapeutic potential associated with these bacterial signaling pathways.

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A Quorum-Sensing System That Regulates Streptococcus pneumoniae Biofilm Formation and Surface Polysaccharide Production

Cited by 45 publications

References 77 publications

Characterization of a Signaling System in Streptococcus mitis That Mediates Interspecies Communication with Streptococcus pneumoniae

Characterization of a Signaling System in Streptococcus mitis That Mediates Interspecies Communication with Streptococcus pneumoniae

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

Targeting peptide‐based quorum sensing systems for the treatment of gram‐positive bacterial infections

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