Pneumococcal meningitis is promoted by single cocci expressing pilus adhesin RrgA

Iovino, Federico; Hammarlöf, Disa L.; Garriss, Geneviève; Brovall, Sarah; Nannapaneni, Priyanka; Henriques‐Normark, Birgitta

doi:10.1172/jci84705

Cited by 44 publications

(55 citation statements)

References 24 publications

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“…We demonstrated that the carrier mutation altered pilus gene regulation and that increased pilus gene expression contributed to increased adherence and internalization by epithelial cells and decreased virulence (i.e., the carrier phenotype). This is the first report of pilus as a major contributor to a carrier phenotype in GAS and differs strikingly from the enhanced invasiveness reported for piliated pneumococci (39,40) and GBS (41,42).…”

Section: Discussioncontrasting

confidence: 92%

Increased Pilus Production Conferred by a Naturally Occurring Mutation Alters Host-Pathogen Interaction in Favor of Carriage in Streptococcus pyogenes

et al. 2017

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Studies of the human pathogen group A Streptococcus (GAS) define the carrier phenotype to be an increased ability to adhere to and persist on epithelial surfaces and a decreased ability to cause disease. We tested the hypothesis that a single amino acid change (Arg135Gly) in a highly conserved sensor kinase (LiaS) of a poorly defined GAS regulatory system contributes to a carrier phenotype through increased pilus production. When introduced into an emm serotype-matched invasive strain, the carrier allele (the gene encoding the LiaS protein with an arginine-toglycine change at position 135 [liaS R135G ]) recapitulated a carrier phenotype defined by an increased ability to adhere to mucosal surfaces and a decreased ability to cause disease. Gene transcript analyses revealed that the liaS mutation significantly altered transcription of the genes encoding pilus in the presence of bacitracin. Elimination of pilus production in the isogenic carrier mutant decreased its ability to colonize the mouse nasopharynx and to adhere to and be internalized by cultured human epithelial cells and restored the virulence phenotype in a mouse model of necrotizing fasciitis. We also observed significantly reduced survival of the isogenic carrier mutant compared to that of the parental invasive strain after exposure to human neutrophils. Elimination of pilus in the isogenic carrier mutant increased the level of survival after exposure to human neutrophils to that for the parental invasive strain. Together, our data demonstrate that the carrier mutation (liaS R135G ) affects pilus expression. Our data suggest new mechanisms of pilus gene regulation in GAS and that the invasiveness associated with pilus gene regulation in GAS differs from the enhanced invasiveness associated with increased pilus production in other bacterial pathogens.

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Section: Discussioncontrasting

confidence: 92%

Increased Pilus Production Conferred by a Naturally Occurring Mutation Alters Host-Pathogen Interaction in Favor of Carriage in Streptococcus pyogenes

et al. 2017

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“…These findings support the hypothesis that in vivo selection drives the loss of covR regulation and the transition to invasive illness, rather than the hypothesis that unique subsets of GAS strains or serotypes possess inherent invasive phenotypes [48]. Such in-host phenotypic variation has been characterized in other organisms, including S. aureus, where a longitudinal study was able to follow a single isolate from carriage to invasive disease [57], and for S. pneumoniae, where meningeal infections have been found to stem from single cocci expressing the pilus protein RrgA [58]. …”

Section: Reconsidering Invasive Illnessmentioning

confidence: 99%

Evolutionary Constraints Shaping Streptococcus pyogenes –Host Interactions

Wilkening

Federle

2017

Trends in Microbiology

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Research on the Gram-positive human-restricted pathogen Streptococcus pyogenes (Group A Streptococcus, GAS) has long focused on invasive illness, the most severe manifestations of GAS infection. Recent advances in descriptions of molecular mechanisms of GAS virulence, coupled with massive sequencing efforts of isolate genomes, have allowed the field to better understand the molecular and evolutionary changes leading to pandemic strains. These findings suggest it necessary to rethink the dogma involving GAS pathogenesis, and that the most productive avenues for research going forward may be investigations into GAS in its normal habitat, the nasopharynx, and its ability to either live with its host in an asymptomatic lifestyle or as an agent of superficial infections. This review will consider these advances, focusing on the natural history of GAS, the evolution of pandemic strains and novel roles for several key virulence factors that may allow the field to better understand their physiological role.

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“…This interaction in turn stimulates multiple signal transduction pathways including phospholipase C, D, A2, mitogen-activated protein kinases (MAPKs) and the phosphatidylinositol-calcium second messenger system, thereby increasing the expression of pneumococcal adhesion receptors pIgR or PECAM-1 [64][65][66]. In addition, pneumococcal pilus-1 adhesin RrgA and pilus-2 adhesin PitB have been implicated in pneumococci-mediated adhesion and invasion of brain endothelial cells and respiratory epithelial cells [67][68][69].…”

Section: Central Nervous Systemmentioning

confidence: 99%

Temporal upregulation of host surface receptors provides a window of opportunity for bacterial adhesion and disease

Shukla

Walters

et al. 2017

Microbiology

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Host surface receptors provide bacteria with a foothold from which to attach, colonize and, in some cases, invade tissue and elicit human disease. In this review, we discuss several key host receptors and cognate adhesins that function in bacterial pathogenesis. In particular, we examine the elevated expression of host surface receptors such as CEACAM-1, CEACAM-6, ICAM-1 and PAFR in response to specific stimuli. We explore how upregulated receptors, in turn, expose the host to a range of bacterial infections in the respiratory tract. It is apparent that exploitation of receptor induction for bacterial adherence is not unique to one body system, but is also observed in the central nervous, gastrointestinal and urogenital systems. Prokaryotic pathogens which utilize this mechanism for their infectivity include Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis and Escherichia coli. A number of approaches have been used, in both in vitro and in vivo experimental models, to inhibit bacterial attachment to temporally expressed host receptors. Some of these novel strategies may advance future targeted interventions for the prevention and treatment of bacterial disease.

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Pneumococcal meningitis is promoted by single cocci expressing pilus adhesin RrgA

Cited by 44 publications

References 24 publications

Increased Pilus Production Conferred by a Naturally Occurring Mutation Alters Host-Pathogen Interaction in Favor of Carriage in Streptococcus pyogenes

Increased Pilus Production Conferred by a Naturally Occurring Mutation Alters Host-Pathogen Interaction in Favor of Carriage in Streptococcus pyogenes

Evolutionary Constraints Shaping Streptococcus pyogenes –Host Interactions

Temporal upregulation of host surface receptors provides a window of opportunity for bacterial adhesion and disease

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