Rgg-Shp regulators are important for pneumococcal colonization and invasion through their effect on mannose utilization and capsule synthesis

Zhi, Xiangyun; Abdullah, Iman Tajer; Gazioglu, Ozcan; Manzoor, Irfan; Shafeeq, Sulman; Kuipers, Oscar P.; Hiller, N. Luisa; Andrew, Peter W.; Yeşilkaya, Hasan

doi:10.1038/s41598-018-24910-1

Cited by 33 publications

(105 citation statements)

References 56 publications

(114 reference statements)

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“…Signaling from cell–cell communication systems phenotypically converge in changes at the population level. These may impact development of biofilms or be associated with modifications in cell surface components such as membrane composition and capsule expression [ 22 , 23 , 43 ]. Cell–cell communication system behaviors may also be accompanied by modification in ability for DNA uptake, fratricide, or bactericidal activity [ 20 , 23 , 31 , 75 , 76 ].…”

Section: Introductionmentioning

confidence: 99%

“…The expression of several cell–cell communication peptides is responsive to levels of host carbohydrates: SHP144 and SHP939 are induced in mannose and galactose and PhrA in galactose. Further, these peptides, as well as PhrA2 and VP1, are repressed in rich media [ 22 , 43 , 44 , 46 ]. The Rgg144/SHP144 system is core; it is activated when the autoinducing peptide SHP144 is imported into the cell and binds Rgg144.…”

Section: Introductionmentioning

confidence: 99%

“…Rgg144 is negatively controlled by master nutritional regulator CodY and glutamine/glutamate metabolism [ 97 , 98 ]. It has an extensive regulon, which includes regulation of genes that have a function in replication, recombination, translation, and nucleotide transport and metabolism [ 43 ]. The most highly induced locus encodes the double-glycine signaling peptide VP1.…”

Section: Introductionmentioning

confidence: 99%

“…The most highly induced locus encodes the double-glycine signaling peptide VP1. It also controls multiple sugar transporters and represses capsule biosynthesis [ 43 , 79 ]. Further, the regulon is sugar specific, with a broad response in mannose and a restricted response in galactose.…”

Section: Introductionmentioning

confidence: 99%

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The pneumococcal social network

et al. 2020

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Gram-positive bacteria employ an array of secreted peptides to control population-level behaviors in response to environmental cues. We review mechanistic and functional features of secreted peptides produced by the human pathogen Streptococcus pneumoniae . We discuss sequence features, mechanisms of transport, and receptors for 3 major categories of small peptides: the double-glycine peptides, the Rap, Rgg, NprR, PlcR, and PrgX (RRNPP)-binding peptides, and the lanthionine-containing peptides. We highlight the impact of factors that contribute to carriage and pathogenesis, specifically genetic diversity, microbial competition, biofilm development, and environmental adaptation. A recent expansion in pneumococcal peptide studies reveals a complex network of interacting signaling systems where multiple peptides are integrated into the same signaling pathway, allowing multiple points of entry into the pathway and extending information content in new directions. In addition, since peptides are present in the extracellular milieu, there are opportunities for crosstalk, quorum sensing (QS), as well as intra- and interstrain and species interactions. Knowledge on the manner that population-level behaviors contribute to disease provides an avenue for the design and development of anti-infective strategies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The pneumococcal social network

et al. 2020

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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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MicroMagnify: A Multiplexed Expansion Microscopy Method for Pathogens and Infected Tissues

Cheng,

Stefani,

Skillman

et al. 2023

Advanced Science

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Super‐resolution optical imaging tools are crucial in microbiology to understand the complex structures and behavior of microorganisms such as bacteria, fungi, and viruses. However, the capabilities of these tools, particularly when it comes to imaging pathogens and infected tissues, remain limited. MicroMagnify (µMagnify) is developed, a nanoscale multiplexed imaging method for pathogens and infected tissues that are derived from an expansion microscopy technique with a universal biomolecular anchor. The combination of heat denaturation and enzyme cocktails essential is found for robust cell wall digestion and expansion of microbial cells and infected tissues without distortion. µMagnify efficiently retains biomolecules suitable for high‐plex fluorescence imaging with nanoscale precision. It demonstrates up to eightfold expansion with µMagnify on a broad range of pathogen‐containing specimens, including bacterial and fungal biofilms, infected culture cells, fungus‐infected mouse tone, and formalin‐fixed paraffin‐embedded human cornea infected by various pathogens. Additionally, an associated virtual reality tool is developed to facilitate the visualization and navigation of complex 3D images generated by this method in an immersive environment allowing collaborative exploration among researchers worldwide. µMagnify is a valuable imaging platform for studying how microbes interact with their host systems and enables the development of new diagnosis strategies against infectious diseases.

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Rgg-Shp regulators are important for pneumococcal colonization and invasion through their effect on mannose utilization and capsule synthesis

Cited by 33 publications

References 56 publications

The pneumococcal social network

The pneumococcal social network

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

MicroMagnify: A Multiplexed Expansion Microscopy Method for Pathogens and Infected Tissues

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