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1.
mSphere ; 6(4): e0038121, 2021 08 25.
Article in English | MEDLINE | ID: mdl-34346700

ABSTRACT

The bacterial genus Staphylococcus comprises a large group of pathogenic and nonpathogenic species associated with an array of host species. Staphylococci are differentiated into coagulase-positive or coagulase-negative groups based on the capacity to promote clotting of plasma, a phenotype historically associated with the ability to cause disease. However, the genetic basis of this important diagnostic and pathogenic trait across the genus has not been examined to date. Here, we selected 54 representative staphylococcal species and subspecies to examine coagulation of plasma derived from six representative host species. In total, 13 staphylococcal species mediated coagulation of plasma from at least one host species including one previously identified as coagulase negative (Staphylococcus condimenti). Comparative genomic analysis revealed that coagulase activity correlated with the presence of a gene (vwb) encoding the von Willebrand binding protein (vWbp) whereas only the Staphylococcus aureus complex contained a gene encoding staphylocoagulase (Coa), the classical mediator of coagulation. Importantly, S. aureus retained vwb-dependent coagulase activity in an S. aureus strain deleted for coa whereas deletion of vwb in Staphylococcus pseudintermedius resulted in loss of coagulase activity. Whole-genome-based phylogenetic reconstruction of the Staphylococcus genus revealed that the vwb gene has been acquired on at least four different occasions during the evolution of the Staphylococcus genus followed by allelic diversification via mutation and recombination. Allelic variants of vWbp from selected coagulase-positive staphylococci mediated coagulation in a host-dependent manner indicative of host-adaptive evolution. Taken together, we have determined the genetic and evolutionary basis of staphylococcal coagulation, revealing vWbp to be its archetypal determinant. IMPORTANCE The ability of some species of staphylococci to promote coagulation of plasma is a key pathogenic and diagnostic trait. Here, we provide a comprehensive analysis of the coagulase positivity of the staphylococci and its evolutionary genetic basis. We demonstrate that the von Willebrand binding protein rather than staphylocoagulase is the archetypal coagulation factor of the staphylococci and that the vwb gene has been acquired several times independently during the evolution of the staphylococci. Subsequently, vwb has undergone adaptive diversification to facilitate host-specific functionality. Our findings provide important insights into the evolution of pathogenicity among the staphylococci and the genetic basis for a defining diagnostic phenotype.


Subject(s)
Bacterial Proteins/genetics , Coagulase/genetics , Coagulase/metabolism , Evolution, Molecular , Staphylococcus/enzymology , Staphylococcus/genetics , Animals , Birds , Blood Coagulation , Genome, Bacterial , Genomics/methods , Horses , Humans , Phylogeny , Rabbits , Staphylococcal Infections/microbiology , Staphylococcal Infections/veterinary , Staphylococcus/classification , Staphylococcus/metabolism , Swine , Virulence Factors/genetics
2.
PLoS Pathog ; 7(10): e1002271, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22022262

ABSTRACT

Bacterial superantigens (SAg) stimulate T-cell hyper-activation resulting in immune modulation and severe systemic illnesses such as Staphylococcus aureus toxic shock syndrome. However, all known S. aureus SAgs are encoded by mobile genetic elements and are made by only a proportion of strains. Here, we report the discovery of a novel SAg staphylococcal enterotoxin-like toxin X (SElX) encoded in the core genome of 95% of phylogenetically diverse S. aureus strains from human and animal infections, including the epidemic community-associated methicillin-resistant S. aureus (CA-MRSA) USA300 clone. SElX has a unique predicted structure characterized by a truncated SAg B-domain, but exhibits the characteristic biological activities of a SAg including Vß-specific T-cell mitogenicity, pyrogenicity and endotoxin enhancement. In addition, SElX is expressed by clinical isolates in vitro, and during human, bovine, and ovine infections, consistent with a broad role in S. aureus infections of multiple host species. Phylogenetic analysis suggests that the selx gene was acquired horizontally by a progenitor of the S. aureus species, followed by allelic diversification by point mutation and assortative recombination resulting in at least 17 different alleles among the major pathogenic clones. Of note, SElX variants made by human- or ruminant-specific S. aureus clones demonstrated overlapping but distinct Vß activation profiles for human and bovine lymphocytes, indicating functional diversification of SElX in different host species. Importantly, SElX made by CA-MRSA USA300 contributed to lethality in a rabbit model of necrotizing pneumonia revealing a novel virulence determinant of CA-MRSA disease pathogenesis. Taken together, we report the discovery and characterization of a unique core genome-encoded superantigen, providing new insights into the evolution of pathogenic S. aureus and the molecular basis for severe infections caused by the CA-MRSA USA300 epidemic clone.


Subject(s)
Community-Acquired Infections/microbiology , Enterotoxins/genetics , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/immunology , Pneumonia, Staphylococcal/microbiology , Superantigens/genetics , Animals , Cattle , Community-Acquired Infections/epidemiology , Evolution, Molecular , Genetic Variation , Humans , Interspersed Repetitive Sequences , Methicillin-Resistant Staphylococcus aureus/metabolism , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Molecular Sequence Data , Phylogeny , Pneumonia, Staphylococcal/epidemiology , Rabbits , Virulence Factors/genetics
3.
Infect Immun ; 79(8): 3074-86, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21576333

ABSTRACT

Cell wall-associated (CWA) proteins made by Gram-positive pathogens play a fundamental role in pathogenesis. Staphylococcus pseudintermedius is a major animal pathogen responsible for the canine skin disease bacterial pyoderma. Here, we describe the bioinformatic analysis of the family of 18 predicted CWA proteins encoded in the genome of S. pseudintermedius strain ED99 and determine their distribution among a phylogenetically diverse panel of S. pseudintermedius clinical isolates and closely related species of the Staphylococcus intermedius group. In parallel, we employed a proteomic approach to identify proteins presented on the surface of strain ED99 in vitro, revealing a total of 60 surface-localized proteins in one or more phases of growth, including 6 of the 18 genome-predicted CWA proteins. Based on these analyses, we selected two CWA proteins (SpsD and SpsL) encoded by all strains examined and investigated their capacity to mediate adherence to extracellular matrix proteins. We discovered that SpsD and SpsL mediated binding of a heterologous host, Lactococcus lactis, to fibrinogen and fibronectin and that SpsD mediated binding to cytokeratin 10, a major constituent of mammalian skin. Of note, the interaction with fibrinogen was host-species dependent, suggestive of a role for SpsD and SpsL in the host tropism of S. pseudintermedius. Finally, we identified IgG specific for SpsD and SpsL in sera from dogs with bacterial pyoderma, implying that both proteins are expressed during infection. The combined genomic and proteomic approach employed in the current study has revealed novel host-pathogen interactions which represent candidate therapeutic targets for the control of bacterial pyoderma.


Subject(s)
Adhesins, Bacterial/metabolism , Bacterial Proteins/analysis , Extracellular Matrix Proteins/metabolism , Host-Pathogen Interactions , Proteome/analysis , Staphylococcus intermedius/chemistry , Staphylococcus intermedius/genetics , Adhesins, Bacterial/genetics , Animals , Bacterial Proteins/genetics , Cell Wall/chemistry , Computational Biology , Dogs , Proteome/genetics
4.
Microbes Infect ; 13(3): 216-25, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21044892

ABSTRACT

Cardiac vegetations result from bacterium-platelet adherence, activation and aggregation, and are associated with increased morbidity and mortality in infective endocarditis. The GPIIb/IIIa and FcγRIIa platelet receptors play a central role in platelet adhesion, activation and aggregation induced by endocarditis pathogens such as Staphylococcus aureus, but the influence of known polymorphisms of these receptors on the pathogenesis of infective endocarditis is unknown. We determined the GPIIIa platelet antigen Pl(A1/A2) and FcγRIIa H131R genotype of healthy volunteers (n = 160) and patients with infective endocarditis (n = 40), and investigated the influence of these polymorphisms on clinical outcome in infective endocarditis and S. aureus-platelet interactions in vitro. Platelet receptor genotype did not correlate with development of infective endocarditis, vegetation characteristics on echocardiogram or the composite clinical end-point of embolism, heart failure, need for surgery or mortality (P > 0.05 for all), even though patients with the GPIIIa Pl(A1/A1) genotype had increased in vivo platelet activation (P = 0.001). Furthermore, neither GPIIIa Pl(A1/A2) nor FcγRIIa H131R genotype influenced S. aureus-induced platelet adhesion, activation or aggregation in vitro (P > 0.05). Taken together, our data suggest that the GPIIIa and FcγRIIa platelet receptor polymorphisms do not influence S. aureus-platelet interactions in vitro or the clinical course of infective endocarditis.


Subject(s)
Blood Platelets/microbiology , Endocarditis/blood , Integrin beta3/genetics , Receptors, IgG/genetics , Staphylococcal Infections/blood , Staphylococcus aureus/physiology , Adult , Aged , Blood Platelets/physiology , Endocarditis/genetics , Endocarditis/microbiology , Female , Host-Pathogen Interactions , Humans , Male , Middle Aged , Platelet Activation , Polymorphism, Genetic , Staphylococcal Infections/genetics , Staphylococcal Infections/microbiology , Statistics, Nonparametric
5.
Genome Biol Evol ; 2: 454-66, 2010 Jul 12.
Article in English | MEDLINE | ID: mdl-20624747

ABSTRACT

Phenotypic biotyping has traditionally been used to differentiate bacteria occupying distinct ecological niches such as host species. For example, the capacity of Staphylococcus aureus from sheep to coagulate ruminant plasma, reported over 60 years ago, led to the description of small ruminant and bovine S. aureus ecovars. The great majority of small ruminant isolates are represented by a single, widespread clonal complex (CC133) of S. aureus, but its evolutionary origin and the molecular basis for its host tropism remain unknown. Here, we provide evidence that the CC133 clone evolved as the result of a human to ruminant host jump followed by adaptive genome diversification. Comparative whole-genome sequencing revealed molecular evidence for host adaptation including gene decay and diversification of proteins involved in host-pathogen interactions. Importantly, several novel mobile genetic elements encoding virulence proteins with attenuated or enhanced activity in ruminants were widely distributed in CC133 isolates, suggesting a key role in its host-specific interactions. To investigate this further, we examined the activity of a novel staphylococcal pathogenicity island (SaPIov2) found in the great majority of CC133 isolates which encodes a variant of the chromosomally encoded von Willebrand-binding protein (vWbp(Sov2)), previously demonstrated to have coagulase activity for human plasma. Remarkably, we discovered that SaPIov2 confers the ability to coagulate ruminant plasma suggesting an important role in ruminant disease pathogenesis and revealing the origin of a defining phenotype of the classical S. aureus biotyping scheme. Taken together, these data provide broad new insights into the origin and molecular basis of S. aureus ruminant host specificity.


Subject(s)
Evolution, Molecular , Ruminants/microbiology , Staphylococcus aureus/classification , Staphylococcus aureus/genetics , Adaptation, Physiological/genetics , Animals , Base Sequence , Cattle , Comparative Genomic Hybridization , DNA, Bacterial/genetics , Ecosystem , Genome, Bacterial , Goats , Host-Pathogen Interactions/genetics , Humans , Interspersed Repetitive Sequences , Phylogeny , Sheep , Species Specificity , Staphylococcus aureus/pathogenicity , Staphylococcus aureus/physiology
6.
Proc Natl Acad Sci U S A ; 106(46): 19545-50, 2009 Nov 17.
Article in English | MEDLINE | ID: mdl-19884497

ABSTRACT

The impact of globalization on the emergence and spread of pathogens is an important veterinary and public health issue. Staphylococcus aureus is a notorious human pathogen associated with serious nosocomial and community-acquired infections. In addition, S. aureus is a major cause of animal diseases including skeletal infections of poultry, which are a large economic burden on the global broiler chicken industry. Here, we provide evidence that the majority of S. aureus isolates from broiler chickens are the descendants of a single human-to-poultry host jump that occurred approximately 38 years ago (range, 30 to 63 years ago) by a subtype of the worldwide human ST5 clonal lineage unique to Poland. In contrast to human subtypes of the ST5 radiation, which demonstrate strong geographic clustering, the poultry ST5 clade was distributed in different continents, consistent with wide dissemination via the global poultry industry distribution network. The poultry ST5 clade has undergone genetic diversification from its human progenitor strain by acquisition of novel mobile genetic elements from an avian-specific accessory gene pool, and by the inactivation of several proteins important for human disease pathogenesis. These genetic events have resulted in enhanced resistance to killing by chicken heterophils, reflecting avian host-adaptive evolution. Taken together, we have determined the evolutionary history of a major new animal pathogen that has undergone rapid avian host adaptation and intercontinental dissemination. These data provide a new paradigm for the impact of human activities on the emergence of animal pathogens.


Subject(s)
Adaptation, Physiological , Host-Pathogen Interactions , Poultry Diseases/microbiology , Poultry/microbiology , Staphylococcal Infections/epidemiology , Staphylococcus aureus/physiology , Animals , Cattle , Disease Outbreaks , Humans , Interspersed Repetitive Sequences , Molecular Sequence Data , Phylogeny , Staphylococcal Infections/microbiology , Staphylococcus aureus/classification , Staphylococcus aureus/genetics
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