Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease

Landwehr-Kenzel, Sybille; Henneke, Philipp

doi:10.3389/fimmu.2014.00519

Cited by 94 publications

(81 citation statements)

References 182 publications

(184 reference statements)

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“…Recent studies on the genomics and virulence of S. agalactiae have identified a range of disease/host-associated genetic traits (84)(85)(86)(87) and mechanisms of virulence (88)(89)(90). In this sense, we hypothesize that there is likely to be a spectrum of genotypes, phenotypes, and virulence strategies used by UPSA and ABSA to colonize and cause infection in the urinary tract; this would parallel knowledge for UPEC (67).…”

Section: Discussionmentioning

confidence: 99%

Discovery and Characterization of Human-Urine Utilization by Asymptomatic-Bacteriuria-Causing Streptococcus agalactiae

et al. 2016

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f Streptococcus agalactiae causes both symptomatic cystitis and asymptomatic bacteriuria (ABU); however, growth characteristics of S. agalactiae in human urine have not previously been reported. Here, we describe a phenotype of robust growth in human urine observed in ABU-causing S. agalactiae (ABSA) that was not seen among uropathogenic S. agalactiae (UPSA) strains isolated from patients with acute cystitis. In direct competition assays using pooled human urine inoculated with equal numbers of a prototype ABSA strain, designated ABSA 1014, and any one of several UPSA strains, measurement of the percentage of each strain recovered over time showed a markedly superior fitness of ABSA 1014 for urine growth. Comparative phenotype profiling of ABSA 1014 and UPSA strain 807, isolated from a patient with acute cystitis, using metabolic arrays of >2,500 substrates and conditions revealed unique and specific L-malic acid catabolism in ABSA 1014 that was absent in UPSA 807. Whole-genome sequencing also revealed divergence in malic enzyme-encoding genes between the strains predicted to impact the activity of the malate metabolic pathway. Comparative growth assays in urine comparing wild-type ABSA and gene-deficient mutants that were functionally inactivated for the malic enzyme metabolic pathway by targeted disruption of the maeE or maeK gene in ABSA demonstrated attenuated growth of the mutants in normal human urine as well as synthetic human urine containing malic acid. We conclude that some S. agalactiae strains can grow in human urine, and this relates in part to malic acid metabolism, which may affect the persistence or progression of S. agalactiae ABU.

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Section: Discussionmentioning

confidence: 99%

Discovery and Characterization of Human-Urine Utilization by Asymptomatic-Bacteriuria-Causing Streptococcus agalactiae

et al. 2016

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“…MFs from the colon of adult mice largely originate from blood monocytes (19). Moreover, the colon is the natural colonization site of GBS, starting early in life (2). Hence, understanding GBS recognition in intestinal MFs is important in the context of host resistance against GBS.…”

Section: Monocyte-derived Intestinal Mfs Require Tlr13 For Gbs Sensingmentioning

confidence: 99%

“…Proper TLR function in resident immune cells, especially tissue macrophages (MFs), is required to hold potentially virulent bacteria in check at mucocutaneous sites (2)(3)(4). Yet, the policing function of MFs, which stabilizes surface niches for colonizing bacteria, and the dangerous hyperinflammatory response of myeloid cells during bacterial spread result from similar interaction principals between bacterial effectors and TLRs.…”

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confidence: 99%

Streptococci Engage TLR13 on Myeloid Cells in a Site-Specific Fashion

Kolter

Feuerstein

Spoeri

et al. 2016

The Journal of Immunology

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International audienceStreptococci are common human colonizers with a species-specific mucocutaneous distribution. At the same time, they are among the most important and most virulent invasive bacterial pathogens. Thus, site-specific cellular innate immunity, which is predominantly executed by resident and invading myeloid cells, has to be adapted with respect to streptococcal sensing, handling, and response. In this article, we show that TLR13 is the critical mouse macrophage (MΦ) receptor in the response to group B Streptococcus, both in bone marrow-derived MΦs and in mature tissue MΦs, such as those residing in the lamina propria of the colon and the dermis, as well as in microglia. In contrast, TLR13 and its chaperone UNC-93B are dispensable for a potent cytokine response of blood monocytes to group B Streptococcus, although monocytes serve as the key progenitors of intestinal and dermal MΦs. Furthermore, a specific role for TLR13 with respect to MΦ function is supported by the response to staphylococci, where TLR13 and UNC-93B limit the cytokine response in bone marrow-derived MΦs and microglia, but not in dermal MΦs. In summary, TLR13 is a critical and site-specific receptor in the single MΦ response to β-hemolytic streptococci

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“…These results suggest that ␤-h/c pigment production is not critical for GBS virulence although numerous in vitro and in vivo studies using cellular or animal models indicated that greater ␤-h/c pigment production is associated with increased virulence (10)(11)(12)(13)(14)(15)18). The pathogenicity of GBS is multifactorial and combines the expression of several factors to result in an overall virulence phenotype that may vary for each isolate (42). In addition, host factors, at the genetic or microbiota level, might contribute to virulence of NH/NP strains that do not express one of the most potent GBS virulence-associated factors.…”

Section: Discussionmentioning

confidence: 91%

Molecular Characterization of Nonhemolytic and Nonpigmented Group B Streptococci Responsible for Human Invasive Infections

et al. 2016

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h Group B Streptococcus (GBS) is a common commensal bacterium in adults, but is also the leading cause of invasive bacterial infections in neonates in developed countries. The ␤-hemolysin/cytolysin (␤-h/c), which is always associated with the production of an orange-to-red pigment, is a major virulence factor that is also used for GBS diagnosis. A collection of 1,776 independent clinical GBS strains isolated in France between 2006 and 2013 was evaluated on specific medium for ␤-h/c activity and pigment production. The genomic sequences of nonhemolytic and nonpigmented (NH/NP) strains were analyzed to identify the molecular basis of this phenotype. Gene deletions or complementations were carried out to confirm the genotype-phenotype association. Sixty-three GBS strains (3.5%) were NH/NP, and 47 of these (74.6%) originated from invasive infections, including bacteremia and meningitis, in neonates or adults. The mutations are localized predominantly in the cyl operon, encoding the ␤-h/c pigment biosynthetic pathway and, in the abx1 gene, encoding a CovSR regulator partner. In conclusion, although usually associated with GBS virulence, ␤-h/c pigment production is not absolutely required to cause human invasive infections. Caution should therefore be taken in the use of hemolysis and pigmentation as criteria for GBS diagnosis in routine clinical laboratory settings. S treptococcus agalactiae, or group B Streptococcus (GBS), is aGram-positive bacterium that is usually an asymptomatic member of the human intestinal and vaginal microbiota. However, GBS is also the leading cause of neonatal sepsis and meningitis in developed countries (1-3) and an emerging pathogen in adults, mostly in the elderly (4, 5). Neonatal infections occur predominantly during delivery by inhalation or ingestion of contaminated secretions of the mother's vagina. Rapid invasive infections may follow, with a mortality rate of up to 10% during the first week of life (early-onset disease [EOD], age of 0 to 6 days) or during the first 3 months of life (late-onset disease [LOD], age of 7 to 89 days). Systematic GBS screening prior to delivery and intrapartum antibiotic prophylaxis have efficiently reduced EOD but not LOD (6), highlighting the need to further improve the diagnosis and treatments.GBS is an extracellular pathogen and one of its characteristics is the secretion of a potent ␤-hemolysin/cytolysin (␤-h/c) (7-9). This ␤-h/c has a central role in balancing the pro-and anti-inflammatory responses of the infected host and is necessary to breach the epithelial and endothelial barriers and the phagolysosome membrane (10-15). Remarkably, the GBS ␤-h/c is unique among Gram-positive pathogens and its production is linked to that of a characteristic orange-to-red pigment. This dual and specific ␤-h/c and pigment phenotype is routinely used in clinical settings to identify GBS isolates (16,17).It was initially proposed that the GBS protein CylE was, in fact, ␤-h/c and that the pigment was a distinct carotenoid-like molecule (18,19). However, it was rece...

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Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease

Cited by 94 publications

References 182 publications

Discovery and Characterization of Human-Urine Utilization by Asymptomatic-Bacteriuria-Causing Streptococcus agalactiae

Discovery and Characterization of Human-Urine Utilization by Asymptomatic-Bacteriuria-Causing Streptococcus agalactiae

Streptococci Engage TLR13 on Myeloid Cells in a Site-Specific Fashion

Molecular Characterization of Nonhemolytic and Nonpigmented Group B Streptococci Responsible for Human Invasive Infections

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