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PubMed2005

Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity.

Intramembrane proteolysis is a new paradigm in biology that controls signaling events throughout evolution. Hydrolysis of peptide bonds is thought to occur within the normally hydrophobic membrane environment, but insights into this unusual activity have been lacking because of difficulty in recapitulating activity in vitro. We have reconstituted intramembrane proteolysis with a pure recombinant substrate and rhomboid proteins in both detergent micelles and artificial membrane environments. Rhomboid proteins from diverse organisms including two model bacteria, a pathogen, an extremophile, and an animal were robustly active in pure form, proving that rhomboids are a new class of enzymes and do not require cofactors to catalyze intramembrane proteolysis. Rhomboid proteins directly recognized their substrates in vitro by the top of the substrate transmembrane domain, displaying specificity apparently reciprocal to that of gamma-secretase, the only other activity known to cleave type-I transmembrane domains. Rhomboid proteases represent a different evolutionary path to a serine protease mechanism and exhibited an inhibitor profile unlike other serine proteases. Intriguingly, activity was dramatically modulated by different membrane phospholipid environments, suggesting a mechanism for regulating these proteases. This analysis promises to help reveal the biochemical mechanisms and biological roles of this most widely conserved membrane protein family.

Animals↗

PubMed2005

Methyltransferase Erm(37) slips on rRNA to confer atypical resistance in Mycobacterium tuberculosis.

Members of the Mycobacterium tuberculosis complex possess a resistance determinant, erm(37) (also termed ermMT), which is a truncated homologue of the erm genes found in a diverse range of drug-producing and pathogenic bacteria. All erm genes examined thus far encode N(6)-monomethyltransferases or N(6),N(6)-dimethyltransferases that show absolute specificity for nucleotide A2058 in 23 S rRNA. Monomethylation at A2058 confers resistance to a subset of the macrolide, lincosamide, and streptogramin B (MLS(B)) group of antibiotics and no resistance to the latest macrolide derivatives, the ketolides. Dimethylation at A2058 confers high resistance to all MLS(B) and ketolide drugs. The erm(37) phenotype fits into neither category. We show here by tandem mass spectrometry that Erm(37) initially adds a single methyl group to its primary target at A2058 but then proceeds to attach additional methyl groups to the neighboring nucleotides A2057 and A2059. Other methyltransferases, Erm(E) and Erm(O), maintain their specificity for A2058 on mycobacterial rRNA. Erm(E) and Erm(O) have a full-length C-terminal domain, which appears to be important for stabilizing the methyltransferases at their rRNA target, and this domain is truncated in Erm(37). The lax interaction of the M. tuberculosis Erm(37) with its rRNA produces a unique methylation pattern and confers resistance to the ketolide telithromycin.

Anti-Bacterial Agents↗

PubMed1998

Periplasmic chaperone recognition motif of subunits mediates quaternary interactions in the pilus.

The class of proteins collectively known as periplasmic immunoglobulin-like chaperones play an essential role in the assembly of a diverse set of adhesive organelles used by pathogenic strains of Gram-negative bacteria. Herein, we present a combination of genetic and structural data that sheds new light on chaperone-subunit and subunit-subunit interactions in the prototypical P pilus system, and provides new insights into how PapD controls pilus biogenesis. New crystallographic data of PapD with the C-terminal fragment of a subunit suggest a mechanism for how periplasmic chaperones mediate the extraction of pilus subunits from the inner membrane, a prerequisite step for subunit folding. In addition, the conserved N- and C-terminal regions of pilus subunits are shown to participate in the quaternary interactions of the mature pilus following their uncapping by the chaperone. By coupling the folding of subunit proteins to the capping of their nascent assembly surfaces, periplasmic chaperones are thereby able to protect pilus subunits from premature oligomerization until their delivery to the outer membrane assembly site.

Adhesins, Bacterial↗

PubMed2005

Selection of Heterodera glycines chorismate mutase-1 alleles on nematode-resistant soybean.

The soybean cyst nematode Heterodera glycines is the most destructive pathogen of soybean in the Unites States. Diversity in the parasitic ability of the nematode allows it to reproduce on nematode-resistant soybean. H. glycines chorismate mutase-1 (Hg-CM-1) is a nematode enzyme with the potential to suppress host plant defense compounds; therefore, it has the potential to enhance the parasitic ability of nematodes expressing the gene. Hg-cm-1 is a member of a gene family where two alleles, Hg-cm-1A and Hg-cm-1B, have been identified. Analysis of the Hg-cm-1 gene copy number revealed that there are multiple copies of Hg-cm-1 alleles in the H. glycines genome. H. glycines inbred lines were crossed to ultimately generate three F2 populations of second-stage juveniles (J2s) segregating for Hg-cm-1A and Hg-cm-1B. Segregation of Hg-cm-1A and 1B approximated a 1:2:1 ratio, which suggested that Hg-cm-1 is organized in a cluster of genes that segregate roughly as a single locus. The F2 H. glycines J2 populations were used to infect nematode-resistant (Hartwig, PI88788, and PI90763) and susceptible (Lee 74) soybean plants. H. glycines grown on Hartwig, Lee 74, and PI90763 showed allelic frequencies similar to Hg-cm-1A/B, but nematodes grown on PI88788 contained predominately Hg-cm-1A allele as a result of a statistically significant drop of Hg-cm-1B in the population. This result suggests that specific Hg-cm-1 alleles, or a closely linked gene, may aid H. glycines in adapting to particular soybean hosts.

Alleles↗

PubMed2003

A naturally occurring recombinant DNA-A of a typical bipartite begomovirus does not require the cognate DNA-B to infect Nicotiana benthamiana systemically.

Species of the genus Begomovirus (family Geminiviridae) found in the western hemisphere typically have a bipartite genome that consists of two 2.6 kb DNA genomic components, DNA-A and DNA-B. We have identified and cloned genomic components of a new tomato-infecting begomovirus from Brazil, for which the name Tomato crinkle leaf yellows virus (TCrLYV) is proposed, and a DNA-A variant of Tomato chlorotic mottle virus (ToCMV-[MG-Bt1]). Sequence analysis revealed that TCrLYV was most closely related to ToCMV, although it was sufficiently divergent to be considered a distinct virus species. Furthermore, these closely related viruses induce distinguishable symptoms in tomato plants. With respect to ToCMV-[MG-Bt1] DNA-A, evidence is presented that suggests a recombinant origin. It possesses a hybrid genome on which the replication compatible module (AC1 and replication origin) was probably donated by ToCMV-[BA-Se1] and the remaining sequences appear to have originated from Tomato rugose mosaic virus (ToRMV). Despite the high degree of sequence conservation with its predecessors, ToCMV-[MG-Bt1] differs significantly in its biological properties. Although ToCMV-[MG-Bt1] DNA-A did not infect tomato plants, it systemically infected Nicotiana benthamiana, induced symptoms of mottling and accumulated viral DNA in the apical leaves in the absence of a cognate DNA-B. The modular rearrangement that resulted in ToCMV-[MG-Bt1] DNA-A may have provided this virus with a more aggressive nature. Our results further support the notion that interspecies recombination may play a significant role in geminivirus diversity and their emergence as agriculturally important pathogens.

Base Sequence↗

PubMed2025

Plasma membrane accessible cholesterol is regulated by ACC1 and lipid droplets.

Proper maintenance of plasma membrane (PM) cholesterol is essential for diverse processes ranging from animal development to pathogen evasion. Despite decades of study, the mechanisms governing cellular cholesterol regulation are incomplete. Using genome-wide screens we find that ACC1, the rate-limiting enzyme in fatty acid biosynthesis, regulates PM cholesterol transport. ACC1 loss causes a ~10-fold increase in PM accessible cholesterol in cells and mice. Mechanistically, we find that ACC1 regulates lipid droplet (LD) catabolism, and LDs are intimately tied to PM accessible cholesterol levels since reductions or elevations in their numbers block or promote cholesterol trafficking, respectively. Furthermore, LDs are required for cholesterol trafficking induced by 25-hydroxycholesterol, a modulator of inflammation and an interferon-stimulated second messenger that protects cells from pathogen invasion. This work identifies an unrecognized role for ACC1 and LDs in cholesterol regulation, which has implications for diseases where LD numbers are altered, from metabolic syndromes to neurodegeneration.

25-hydroxycholesterol↗

PubMed2006

The response regulator ResD modulates virulence gene expression in response to carbohydrates in Listeria monocytogenes.

Listeria monocytogenes is a versatile bacterial pathogen that is able to accommodate to diverse environmental and host conditions. Presently, we have identified a L. monocytogenes two-component response regulator, ResD that is required for the repression of virulence gene expression known to occur in the presence of easily fermentable carbohydrates not found inside host organisms. Structurally and functionally, ResD resembles the respiration regulator ResD in Bacillus subtilis as deletion of the L. monocytogenes resD reduces respiration and expression of cydA, encoding a subunit of cytochrome bd. The resD mutation also reduces expression of mptA encoding the EIIABman component of a mannose/glucose-specific PTS system, indicating that ResD controls sugar uptake. This notion was supported by the poor growth of resD mutant cells that was alleviated by excess of selected carbohydrates. Despite the growth deficient phenotype of the mutant in vitro the mutation did not affect intracellular multiplication in epithelial or macrophage cell lines. When examining virulence gene expression we observed traditional induction by charcoal in both mutant and wild-type cells whereas the repression observed in wild-type cells by fermentable carbohydrates did not occur in resD mutant cells. Thus, ResD is a central regulator of L. monocytogenes when present in the external environment.

Animals↗

PubMed2006

Mucosal defences against orally acquired protozoan parasites, emphasis on Toxoplasma gondii infections.

Protozoan parasites that gain access to the host through the mucosal tissue of the alimentary tract may influence the development of intestinal inflammatory disorders. Despite the diversity of the extracellular and intracellular protozoan pathogens discussed in this review, our current understanding of the mechanisms involved in the immune response indicates that a common exuberant immune response to rid the host of these agents is elicited. This robust inflammatory response is orchestrated both by cells from parenchymatous origin such as intestinal epithelial cells and by cells from the haematopoietic system such as macrophages, dendritic cells and lymphocytes. This inflammatory immune response is controlled by a series of regulatory mechanisms in most species. When this balance is no longer evident, an inflammation of the intestine may occur, leading to acute gastritis and diarrhoea and that would add pathological effects to those because of the pathogen itself.

Animals↗

PubMed2006

Multilocus sequence typing for global surveillance of meningococcal disease.

The global surveillance of bacterial pathogens is particularly important for bacteria with diverse and dynamic populations that cause periodic epidemics or pandemics. The isolate characterization methods employed for surveillance should: (1) generate unambiguous data; (2) be readily implemented in a variety of scenarios and be reproducible among laboratories; (3) be scalable and preferably available in a high throughput format; and (4) be cost effective. Multilocus sequence typing (MLST) was designed to meet these criteria and has been implemented effectively for a wide range of microorganisms. The 'Impact of meningococcal epidemiology and population biology on public health in Europe (EU-MenNet)' project had amongst its objectives: (1) to disseminate meningococcal MLST and sequence-based typing throughout Europe by establishing a centre for training and data generation, and (2) to produce a comprehensive Europe-wide picture of meningococcal disease epidemiology for the first time. Data produced from the project have shown the distribution of a relatively small number of STs, clonal complexes and PorA types that account for a large proportion of the disease-associated isolates in Europe. The project demonstrates how molecular typing can be combined with epidemiological data via the Internet for global disease surveillance.

Computational Biology↗

PubMed1999

Understanding the mechanism of action of bacterial superantigens from a decade of research.

In the face of the unique diversity and plasticity of the immune system pathogenic organisms have developed multiple mechanisms in adaptation to their hosts, including the expression of a particular class of molecules called superantigens. Bacterial superantigens are the most potent stimulators of T cells. The functional consequences of the expression of superantigens by bacteria can be extended not only to T lymphocytes, but also to B lymphocytes and to cells of the myeloid compartment, including antigen-presenting cells and phagocytes. The biological effects of bacterial superantigens as well as their molecular aspects have now been studied for a decade. Although there is still a long way to go to clearly understand the role these molecules play in the establishment of disease, recently acquired knowledge of their biochemistry now offers unique experimental opportunities in defining the molecular rules of T-cell activation. Here, we present some of the most recent functional and molecular aspects of the interaction of bacterial superantigens with MHC class II molecules and the T-cell receptor.

Animals↗

PubMed2000

Carbapenemases of Chryseobacterium (Flavobacterium) meningosepticum: distribution of blaB and characterization of a novel metallo-beta-lactamase gene, blaB3, in the type strain, NCTC 10016.

Genes encoding carbapenemases in 15 reference strains of Chryseobacterium (Flavobacterium) meningosepticum from the United Kingdom National Collection of Type Cultures and in one recent clinical isolate were investigated. All the strains hydrolyzed imipenem, but their levels of resistance to carbapenems varied, with imipenem and meropenem MICs ranging from 2 to >32 microg/ml. The blaB gene, which encodes a molecular-class B carbapenemase, was detected in only six reference strains and in clinical isolate 97/P/5448. The gene from 97/P/5448 had 98% nucleotide identity with the published sequence of blaB (from strain NCTC 10585) and was designated blaB2. A distinct carbapenemase gene, designated blaB3, was cloned from the type strain of C. meningosepticum, NCTC 10016. blaB3 had an open reading frame of 750 bp with 82% nucleotide identity to blaB and blaB2 and encoded a beta-lactamase of 249 amino acids, including the putative signal peptide. This beta-lactamase showed 87.6 and 86.7% amino acid homology with BlaB and BlaB2, respectively. blaB3 was detected in one other reference strain besides NCTC 10016, but the genetic basis of the carbapenemase activity detected in the other seven reference strains was not defined. Thus, neither blaB nor blaB3 was ubiquitous in the strains of C. meningosepticum studied, indicating that the reference strains may represent more than one bacterial species, each with its own intrinsic metallo-beta-lactamase. Further taxonomic studies of C. meningosepticum are necessary to resolve this topic. Chryseobacterium spp. are environmental organisms and occasional opportunist pathogens. They apparently represent a reservoir of diverse metallo-beta-lactamases, which potentially spread to gram-negative bacteria of greater clinical significance.

Amino Acid Sequence↗

PubMed1997

Bacterial persistence and expression of disease.

A considerable body of experimental and clinical evidence supports the concept that difficult-to-culture and dormant bacteria are involved in latency of infection and that these persistent bacteria may be pathogenic. This review includes details on the diverse forms and functions of individual bacteria and attempts to make this information relevant to the care of patients. A series of experimental studies involving host-bacterium interactions illustrates the probability that most bacteria exposed to a deleterious host environment can assume a form quite different from that of a free-living bacterium. A hypothesis is offered for a kind of reproductive cycle of morphologically aberrant bacteria as a means to relate their diverse tissue forms to each other. Data on the basic biology of persistent bacteria are correlated with expression of disease and particularly the mechanisms of both latency and chronicity that typify certain infections. For example, in certain streptococcal and nocardial infections, it has been clearly established that wall-defective forms can be induced in a suitable host. These organisms can survive and persist in a latent state within the host, and they can cause pathologic responses compatible with disease. A series of cases illustrating idiopathic conditions in which cryptic bacteria have been implicated in the expression of disease is presented. These conditions include nephritis, rheumatic fever, aphthous stomatitis, idiopathic hematuria, Crohn's disease, and mycobacterial infections. By utilizing PCR, previously nonculturable bacilli have been identified in patients with Whipple's disease and bacillary angiomatosis. Koch's postulates may have to be redefined in terms of molecular data when dormant and nonculturable bacteria are implicated as causative agents of mysterious diseases.

Animals↗

PubMed2006

Evidence for novel pH-dependent regulation of Candida albicans Rim101, a direct transcriptional repressor of the cell wall beta-glycosidase Phr2.

Candida albicans is a commensal fungus of mucosal surfaces that can cause disease in susceptible hosts. One aspect of the success of C. albicans as both a commensal and a pathogen is its ability to adapt to diverse environmental conditions, including dramatic variations in environmental pH. The response to a neutral-to-alkaline pH change is controlled by the Rim101 signal transduction pathway. In neutral-to-alkaline environments, the zinc finger transcription factor Rim101 is activated by the proteolytic removal of an inhibitory C-terminal domain. Upon activation, Rim101 acts to induce alkaline response gene expression and repress acidic response gene expression. Previously, recombinant Rim101 was shown to directly bind to the alkaline-pH-induced gene PHR1. Here, we demonstrate that endogenous Rim101 also directly binds to the alkaline-pH-repressed gene PHR2. Furthermore, we find that of the three putative binding sites, only the -124 site and, to a lesser extent, the -51 site play a role in vivo. In C. albicans, the predicted Rim101 binding site was thought to be CCAAGAA, divergent from the GCCAAG site defined in Aspergillus nidulans and Saccharomyces cerevisiae. Our results suggest that the Rim101 binding site in C. albicans is GCCAAGAA, but slight variations are tolerated in a context-dependent fashion. Finally, our data suggest that Rim101 activity is governed not only by proteolytic processing but also by an additional mechanism not previously described.

Binding Sites↗

PubMed2001

Antigenic variation of Anaplasma marginale: major surface protein 2 diversity during cyclic transmission between ticks and cattle.

The rickettsial pathogen Anaplasma marginale expresses a variable immunodominant outer membrane protein, major surface protein 2 (MSP2), involved in antigenic variation and long-term persistence of the organism in carrier animals. MSP2 contains a central hypervariable region of about 100 amino acids that encodes immunogenic B-cell epitopes that induce variant-specific antibodies during infection. Previously, we have shown that MSP2 is encoded on a polycistronic mRNA transcript in erythrocyte stages of A. marginale and defined the structure of the genomic expression site for this transcript. In this study, we show that the same expression site is utilized in stages of A. marginale infecting tick salivary glands. We also analyzed the variability of this genomic expression site in Oklahoma strain A. marginale transmitted from in vitro cultures to cattle and between cattle and ticks. The structure of the expression site and flanking regions was conserved except for sequence that encoded the MSP2 hypervariable region. At least three different MSP2 variants were encoded in each A. marginale population. The major sequence variants did not change on passage of A. marginale between culture, acute erythrocyte stage infections, and tick salivary glands but did change during persistent infections of cattle. The variant types found in tick salivary glands most closely resembled those present in bovine blood at the time of acquisition of infection, whether infection was acquired from an acute or from a persistent rickettsemia. These variations in structure of an expression site for a major, immunoprotective outer membrane protein have important implications for vaccine development and for obtaining an improved understanding of the mechanisms of persistence of ehrlichial infections in humans, domestic animals, and reservoir hosts.

Anaplasma↗

PubMed2003

Effector ExoU from the type III secretion system is an important modulator of gene expression in lung epithelial cells in response to Pseudomonas aeruginosa infection.

Pseudomonas aeruginosa is an important pathogen in immunocompromised patients and secretes a diverse set of virulence factors that aid colonization and influence host cell defenses. An important early step in the establishment of infection is the production of type III-secreted effectors translocated into host cells by the bacteria. We used cDNA microarrays to compare the transcriptomic response of lung epithelial cells to P. aeruginosa mutants defective in type IV pili, the type III secretion apparatus, or in the production of specific type III-secreted effectors. Of the 18,000 cDNA clones analyzed, 55 were induced or repressed after 4 h of infection and could be classified into four different expression patterns. These include (i) host genes that are induced or repressed in a type III secretion-independent manner (32 clones), (ii) host genes induced specifically by ExoU (20 clones), and (iii) host genes induced in an ExoU-independent but type III secretion dependent manner (3 clones). In particular, ExoU was essential for the expression of immediate-early response genes, including the transcription factor c-Fos. ExoU-dependent gene expression was mediated in part by early and transient activation of the AP1 transcription factor complex. In conclusion, the present study provides a detailed insight into the response of epithelial cells to infection and indicates the significant role played by the type III virulence mechanism in the initial host response.

Bacterial Proteins↗

PubMed2001

Display of passenger proteins on the surface of Escherichia coli K-12 by the enterohemorrhagic E. coli intimin EaeA.

Intimins are members of a family of bacterial adhesins from pathogenic Escherichia coli which specifically interact with diverse eukaryotic cell surface receptors. The EaeA intimin from enterohemorrhagic E. coli O157:H7 contains an N-terminal transporter domain, which resides in the bacterial outer membrane and promotes the translocation of four C-terminally attached passenger domains across the bacterial cell envelope. We investigated whether truncated EaeA intimin lacking two carboxy-terminal domains could be used as a translocator for heterologous passenger proteins. We found that a variant of the trypsin inhibitor Ecballium elaterium trypsin inhibitor II (EETI-II), interleukin 4, and the Bence-Jones protein REI(v) were displayed on the surface of E. coli K-12 via fusion to truncated intimin. Fusion protein net accumulation in the outer membrane could be regulated over a broad range by varying the cellular amount of suppressor tRNA that is necessary for translational readthrough at an amber codon residing within the truncated eaeA gene. Intimin-mediated adhesion of the bacterial cells to eukaryotic target cells could be mimicked by surface display of a short fibrinogen receptor binding peptide containing an arginine-glycine-aspartic acid sequence motif, which promoted binding of E. coli K-12 to human platelets. Cells displaying a particular epitope sequence fused to truncated intimin could be enriched 200,000-fold by immunofluorescence staining and fluorescence-activated cell sorting in three sorting rounds. These results demonstrate that truncated intimin can be used as an anchor protein that mediates the translocation of various passenger proteins through the cytoplasmic and outer membranes of E. coli and their exposure on the cell surface. Intimin display may prove a useful tool for future protein translocation studies with interesting biological and biotechnological ramifications.

Adhesins, Bacterial↗

PubMed1999

Phylogenetic relationships of varieties and geographical groups of the human pathogenic fungus Histoplasma capsulatum Darling.

The phylogeny of 46 geographically diverse Histoplasma capsulatum isolates representing the three varieties capsulatum, duboisii, and farciminosum was evaluated using partial DNA sequences of four protein coding genes. Parsimony and distance analysis of the separate genes were generally congruent and analysis of the combined data identified six clades: (i) class 1 North American H. capsulatum var. capsulatum, (ii) class 2 North American H. capsulatum var. capsulatum, (iii) Central American H. capsulatum var. capsulatum, (iv) South American H. capsulatum var. capsulatum group A, (v) South American H. capsulatum var. capsulatum group B, and (vi) H. capsulatum var. duboisii. Although the clades were generally well supported, the relationships among them were not resolved and the nearest outgroups (Blastomyces and Paracoccidioides) were too distant to unequivocally root the H. capsulatum tree. H. capsulatum var. farciminosum was found within the South American H. capsulatum var. capsulatum group A clade. With the exception of the South American H. capsulatum var. capsulatum group A clade, genetic distances within clades were an order of magnitude lower than those between clades, and each clade was supported by a number of shared derived nucleotide substitutions, leading to the conclusion that each clade was genetically isolated from the others. Under a phylogenetic species concept based on possession of multiple shared derived characters, as well as concordance of four gene genealogies, H. capsulatum could be considered to harbor six species instead of three varieties.

AIDS-Related Opportunistic Infections↗

PubMed2005

Cytotoxin and pyrogenic toxin superantigen gene profiles of Staphylococcus aureus associated with subclinical mastitis in dairy cows and relationships with macrorestriction genomic profiles.

A set of 84 Staphylococcus aureus isolates collected from the milk of cows with subclinical mastitis in Asturias (a cattle region of Spain) and six control strains were tested for sequences of genes encoding hemolysins (hla, hlb, hld, hlg, and hlg-2), leukotoxins (lukPV, lukM, and lukED), toxic shock syndrome toxin (tst), and enterotoxins (sea to see, seg to ser, and seu) by conventional and multiplex PCR. It was found that 84, 83, 11, and 39 isolates carried some type of hl, luk, tst, or se gene, respectively, which were arranged in 14 exotoxin genotypes. All of the isolates were negative for lukPV, hlg, sea, sed, see, sej, sek, sep, seq, and ser. Two gene groupings could be related with pathogenicity islands-[lukED, seg, sei, sem, sen, seo +/- seu] with Sabeta-1 and [tst, sec, sel] with SaPIbov, present in 45 and 13.1% of the isolates, respectively-while 11.9% of them carried both islands. Only one contained seb (together with upsilonSabeta-1), and another contained seh (together with lukED). The isolates were also analyzed by pulsed-field gel electrophoresis performed with SmaI. Thirty-nine SmaI profiles (similarity coefficient [S] = 0.94 to 0.21) were differentiated; 12, 1, and 10 of these, respectively, were generated by isolates presumptively carrying Sabeta-1, SaPIbov, or both. Five SmaI profiles (S > or = 0.8) formed a cluster, which contained 20 and 10 isolates carrying one (upsilonSabeta-1) or both islands. These data show the high frequency of genes encoding cytotoxins and pyrogenic toxin superantigens, their relationship with pathogenicity islands, and their distribution among a diversity of genetic types of S. aureus related to subclinical mastitis.

Animals↗