Group B streptococcal haemolysin and pigment, a tale of twins

Rosa-Fraile, Manuel; Dramsi, Shaynoor; Spellerberg, Barbara

doi:10.1111/1574-6976.12071

Cited by 83 publications

(72 citation statements)

References 155 publications

(287 reference statements)

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“…Three-quarters (26/34) of the NH/NP strains harbored a mutation in the cyl operon, confirming its central function for the synthesis, maturation, and export of the ␤-h/c pigment (9,11,22,36). Eight of those strains carry an IS element in the cyl operon, among which six correspond to an IS1381 element previously identified in four clinical NH/NP isolates (21,30).…”

Section: Discussionsupporting

confidence: 52%

“…These two phenotypic characteristics have been used historically for GBS diagnosis, and the current view is that they are essential for virulence (8,9). We tested this assumption by analyzing a large collection of documented GBS human clinical isolates.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the proposed synthesis pathway (9,11), this might suggest that the presence of ornithine is essential for both pigmentation and hemolytic activity, whereas the absence of rhamnose mostly affects hemolysis. Further chemical analysis would greatly improve our understanding of the structure-function of this rhamnolipid toxin (9,11,20), which is unrelated to the known Gram-positive poreforming toxins (45)(46)(47)(48). Lastly, we confirmed that the ABC transporter encoded by cylAB is critical for hemolysis and pigmentation (22).…”

Section: Discussionmentioning

confidence: 99%

“…GBS is an extracellular pathogen and one of its characteristics is the secretion of a potent ␤-hemolysin/cytolysin (␤-h/c) (7)(8)(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)(11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

“…However, it was recently established that the ␤-h/c and the pigment correspond to a unique molecule called granadaene (9,11), a 676-Da ornithine rhamno-polyene (11,20). Granadaene may be entirely synthesized by the 12 genes of the cyl operon (11,19,21).…”

mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2016

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Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA

et al. 2020

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Confronted with the rapid evolution and dissemination of antibiotic resistance, there is an urgent need to develop alternative treatment strategies for drug‐resistant pathogens. Here, an unconventional approach is presented to restore the susceptibility of methicillin‐resistant S. aureus (MRSA) to a broad spectrum of conventional antibiotics via photo‐disassembly of functional membrane microdomains. The photo‐disassembly of microdomains is based on effective photolysis of staphyloxanthin, the golden carotenoid pigment that gives its name. Upon pulsed laser treatment, cell membranes are found severely disorganized and malfunctioned to defense antibiotics, as unveiled by membrane permeabilization, membrane fluidification, and detachment of membrane protein, PBP2a. Consequently, the photolysis approach increases susceptibility and inhibits development of resistance to a broad spectrum of antibiotics including penicillins, quinolones, tetracyclines, aminoglycosides, lipopeptides, and oxazolidinones. The synergistic therapy, without phototoxicity to the host, is effective in combating MRSA both in vitro and in vivo in a mice skin infection model. Collectively, this endogenous chromophore‐targeted phototherapy concept paves a novel platform to revive conventional antibiotics to combat drug‐resistant S. aureus infections as well as to screen new lead compounds.

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Bacterial Secondary Metabolites Embedded in Producer Cell Membranes and Antibiotics Targeting Their Biosynthesis

Xia,

Xiang,

Shi

2024

ChemMedChem

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The bacterial cell membrane primarily houses lipids, carbohydrates, and proteins forming a barrier and interface that maintains cellular integrity, supports homeostasis, and senses environmental changes. Compared to lipid components and excreted secondary metabolites, compounds embedded in the producer cell membrane are often overlooked due to their low abundance and niche‐specific functions. The accumulation of findings has led to an increased appreciation of their crucial roles in bacterial cell biochemistry, physiology, and ecology, as well as their impact on mutualistic and pathogenic bacteria‐eukaryote interactions. This review highlights the structures, biosynthesis, regulation, and ecological functions of membrane‐embedded secondary metabolites. It also discusses antibiotics that target their biosynthetic pathways, aiming to inspire the development of antibiotics specific to pathogenic bacteria without harming human cells.

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Group B streptococcal haemolysin and pigment, a tale of twins

Cited by 83 publications

References 155 publications

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

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

Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA

Bacterial Secondary Metabolites Embedded in Producer Cell Membranes and Antibiotics Targeting Their Biosynthesis

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