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PubMed1990

Staphylococcal opsonization and anti-Staphylococcus aureus IgG subclass antibodies in patients with severe or recurrent S. aureus infections.

Opsonization of Staphylococcus aureus (Oxford strain) and specific IgG subclass antibodies against formalised staphylococci were measured in plasmas from 27 patients with significant S. aureus infections and 35 healthy adults and 15 children. There were no statistically significant differences in the IgG2 and IgG4 levels between two groups and IgG3 was not detected, but the median plasma IgG1 level was significantly higher in patients with staphylococcal infections (P less than 0.00003). The concentration of IgG2 anti-S. aureus antibodies was 25-47 times greater than that of IgG1. If plasmas were decomplemented, the raised IgG1 levels were associated with increased opsonophagocytosis by normal neutrophils (P less than 0.0002).

Abscess↗
PubMed2004

Internalization of Staphylococcus aureus by human keratinocytes.

Staphylococcus aureus is among the most important human pathogens and causes various superficial and systemic infections. The ability of S. aureus to be internalized by, and survive within, host cells, such as keratinocytes, may contribute to the development of persistent or chronic infections and may finally lead to deeper tissue infections or dissemination. To examine the mechanisms of internalization of S. aureus by keratinocytes, isogenic mutants lacking fibronectin-binding proteins (FnBPs), a recombinant protein consisting of the fibronectin-binding domain of S. aureus FnBPs, and an anti-alpha5beta1 antibody were used in cocultures with immortalized keratinocytes and primary keratinocytes. We found that internalization of S. aureus by immortalized keratinocytes requires bacterial FnBPs and is mediated by the major fibronectin-binding integrin alpha5beta1. In contrast to internalization by immortalized keratinocytes, internalization of S. aureus by primary keratinocytes could occur through FnBP-dependent and -independent pathways. S. aureus clumping factor B (ClfB), which was recently determined to bind to epithelial cells, was not involved in the uptake of this bacterium by keratinocytes. The identification of an alternate uptake pathway, which is independent of S. aureus FnBPs and host cell alpha5beta1, has important implications for the design of therapies targeted to bacterial uptake by host cells.

Adhesins, Bacterial↗
PubMed1980

Chemotaxigenesis by encapsulated Staphylococcus aureus M.

Although encapsulated Staphylococcus aureus M is not opsonized by normal human serum, as a chemotaxigen this organism behaved similarly to an unencapsulated variant strain. For optimal chemotaxigenesis, an intact classical complement pathway was required, and C5a appeared to be the major chemotaxin.

Chemotactic Factors↗
PubMed1985

Maintenance of D-alanine ester substitution of lipoteichoic acid by reesterification in Staphylococcus aureus.

Toluene-treated Staphylococcus aureus cells did not synthesize teichoic acid and lipoteichoic acid under the conditions used. The organism displayed, however, a high capacity of incorporating D-[14C]alanine into previously formed polymers. The reaction was dependent on ATP and enhanced by magnesium ions. The incorporation rate into lipoteichoic acid correlated with the rate of loss of alanine ester which occurred through transfer to teichoic acid and base-catalyzed hydrolysis. At pH 6.5 the loss (20% within 4 h) was completely compensated for by reesterification. At pH 7.5 the loss was 60%, but by accelerated incorporation it was reduced to 10%. Incorporation was also enhanced when the original substitution of lipoteichoic acid was lowered by previous growth of S. aureus at high salt concentration. The newly added alanine was randomly distributed along the poly(glycerophosphate) chain. The decreased alanine substitution of lipoteichoic acid after growth at high salt concentration was shown to result from a direct inhibition of alanine incorporation.

Adenosine Triphosphate↗
PubMed2006

Mycotic pseudoaneurysm and purulent pericarditis attributable to methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus is now a common isolate of community-acquired staphylococcal infections. We present the first case of concomitant mycotic pseudoaneurysm and purulent pericarditis caused by methicillin-resistant S. aureus. The isolate was found to be SCCmec type I, sequence type 8, and to carry the PVL gene. The patient was successfully treated with a combined surgical and medical approach.

Adult↗
PubMed2005

Analysis of the genetic variability of virulence-related loci in epidemic clones of methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) isolates have previously been classified into major epidemic clonal types by pulsed-field gel electrophoresis in combination with multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec typing. We aimed to investigate whether genetic variability in potentially polymorphic domains of virulence-related factors could provide another level of differentiation in a diverse collection of epidemic MRSA clones. The target regions of strains representative of epidemic clones and genetically related methicillin-susceptible S. aureus isolates from the 1960s that were sequenced included the R domains of clfA and clfB; the D, W, and M regions of fnbA and fnbB; and three regions in the agr operon. Sequence variation ranged from very conserved regions, such as those for RNAIII and the agr interpromoter region, to the highly polymorphic R regions of the clf genes. The sequences of the clf R domains could be grouped into six major sequence types on the basis of the sequences in their 3' regions. Six sequence types were also observed for the fnb sequences at the amino acid level. From an evolutionary point of view, it was interesting that a small DNA stretch at the 3' clf R-domain sequence and the fnb sequences agreed with the results of MLST for this set of strains. In particular, clfB R-domain sequences, which had a high discriminatory capacity and with which the types distinguished were congruent with those obtained by other molecular typing methods, have potential for use for the typing of S. aureus. Clone- and strain-specific sequence motifs in the clf and fnb genes may represent useful additions to a typing methodology with a DNA array.

Adhesins, Bacterial↗
PubMedDate not supplied

Elimination of Staphylococcus aureus in hemodialysis patients.

Staphylococcus aureus infection and its complications are of great concern in the care of hemodialysis patients. Nasal contamination with S. aureus seems to be the main source of cutaneous contamination. The decontamination and recontamination of the skin of hemodialysis patients after using mupirocin nasal ointment was followed in a placebo control study. After 10 days of therapy with mupirocin nasal ointment, 25 of 33 (73%) patients were free of nasal S. aureus contamination in the nares (control subjects 2 of 21, 10%). At the same time, the prevalence of positive skin cultures for S. aureus decreased from 30 of 33 (90%) to 11 of 33 (33%) patients. However, during the ensuing 130 days, 14 of 25 (58%) patients with negative nasal cultures became recontaminated, while the skin became recontaminated in 11 of 22 (50%) patients. In 10 of 14 S. aureus recontaminated patients the original S. aureus lysotype was documented by specific phage reaction. Four of fourteen patients had a new S. aureus lysotype. Mupirocin nasal ointment eradicated S. aureus transiently in 75% of the patients but continuously in only 11 of 33 (30%) patients.

Administration, Intranasal↗
PubMed2004

Vancomycin-resistant Staphylococcus aureus--New York, 2004.

Staphylococcus aureus is a common cause of hospital- and community-acquired infections. The development of vancomycin-resistant enterococci in 1988 led the way to the emergence of vancomycin-resistant S. aureus (VRSA) (minimum inhibitory concentration [MIC] > or =32 microg/mL [3]), first recognized in 2002. This report describes the third documented clinical isolate of VRSA from a patient in the United States and provides evidence of failure to detect this VRSA by commonly used automated antimicrobial susceptibility testing.

Cross Infection↗
PubMed1999

Fibronectin binding protein and host cell tyrosine kinase are required for internalization of Staphylococcus aureus by epithelial cells.

Staphylococcus aureus expresses several surface proteins that promote adherence to host cell extracellular matrix proteins, including fibronectin (Fn). Since this organism has recently been shown to be internalized by nonprofessional phagocytes, a process that typically requires high-affinity binding to host cell receptors, we investigated the role of its Fn binding proteins (FnBPs) and other surface proteins in internalization by the bovine mammary gland epithelial cell line (MAC-T). Efficient internalization of S. aureus 8325-4 required expression of FnBPs; an isogenic mutant (DU5883), not expressing FnBPs, was reduced by more than 95% in its ability to invade MAC-T cells. Moreover, D3, a synthetic peptide derived from the ligand binding domain of FnBP, inhibited the internalization of the 8325-4 strain in a dose-dependent fashion and the efficiency of staphylococcal internalization was partially correlated with Fn binding ability. Interestingly, Fn also inhibited the internalization and adherence of S. aureus 8325-4 in a dose-dependent manner. In contrast to internalization, adherence of DU5883 to MAC-T was reduced by only approximately 40%, suggesting that surface binding proteins, other than FnBPs, can mediate bacterial adherence to cells. Adherence via these proteins, however, does not necessarily result in internalization of the staphylococci. An inhibitor of protein tyrosine kinase, genistein, reduced MAC-T internalization of S. aureus by 95%, indicating a requirement for a host signal transduction system in this process. Taken together, these results indicate that S. aureus invades nonprofessional phagocytes by a mechanism requiring interaction between FnBP and the host cell, leading to signal transduction and subsequent rearrangement of the host cell cytoskeleton.

Adhesins, Bacterial↗
PubMed2002

Staphylococcus aureus bacteremia and endocarditis.

Staphylococcus aureus is a leading cause of bacteremia and endocarditis. Over the past several years, the frequency of S. aureus bacteremia (SAB) has increased dramatically. This increasing frequency, coupled with increasing rates of antibiotic resistance, has renewed interest in this serious, common infection. S. aureus is a unique pathogen because of its virulent properties, its protean manifestations, and its ability to cause endocarditis on architecturally normal cardiac valves. Although the possibility of underlying endocarditis arises in virtually every patient with SAB, only a minority of bacteremic patients will actually have cardiac involvement. Distinguishing patients with S. aureus infective endocarditis (IE) from those with uncomplicated SAB is essential, but often difficult. In this review, the authors summarize recent changes in the epidemiology of SAB and IE, discuss the challenges in distinguishing SAB from IE, and discuss current trends in the management of patients with SAB and IE.

Bacteremia↗
PubMed2002

Analysis of Ebh, a 1.1-megadalton cell wall-associated fibronectin-binding protein of Staphylococcus aureus.

In order for Staphylococcus aureus to adhere to host extracellular matrix (ECM) substrates, it elicits a wide range of surface proteins. We have characterized a novel approximately 1.1-MDa protein in S. aureus, termed Ebh (for ECM-binding protein homologue), which has homology to other ECM-binding proteins. Ebh consists of several domains, including a large central region with 44 imperfect repeats of 126 amino acids. Expression analysis revealed ebh to be growth phase regulated and repressed by agr. A fragment of the central repeat region of Ebh was cloned, overexpressed, and used in ligand-binding studies to determine Ebh function. The recombinant protein was found to specifically bind human fibronectin. Ebh is produced during human infection since serum samples taken from patients with confirmed S. aureus infections were found to contain anti-Ebh antibodies. Localization studies revealed Ebh to be cell envelope associated and is proposed to form a specialized surface structure involved in cellular adhesion.

Abscess↗
PubMed2001

Unusual inducible cross resistance to macrolides, lincosamides, and streptogramins B by methylase production in clinical isolates of Staphylococcus aureus.

Clinical strains of Staphylococcus aureus UCN7 and UCN8 were inducibly resistant to erythromycin, clindamycin, lincomycin, and quinupristin. This unusual inducible MLS(B) resistance was due to the presence of an erm(A) or an erm(B) gene, which both encode a ribosomal methylase, in S. aureus UCN8 and UCN7, respectively. The inducible cross resistance expressed by S. aureus UCN8 was associated with an 83-bp deletion in the attenuator of the erm(A) gene that removed the second of the two leader peptides and several inverted repeats. The presence of an inducible erm(B) gene in S. aureus UCN7 conferred a cross-resistance MLS(B) phenotype, similar to that usually observed in streptococci. Therefore, in S. aureus, besides the classical inducible MLS(B) phenotype characterized by inducible resistance to 14- to 15-membered ring macrolides, an additional type of inducible cross resistance to macrolides, lincosamides, and streptogramins B due to variants of erm(A) or erm(B) genes exist.

Anti-Bacterial Agents↗
PubMed1989

Low-level methicillin resistance in strains of Staphylococcus aureus.

Two strains of Staphylococcus aureus expressing borderline or low-level methicillin resistance by one or more in vitro test methods were examined for resistance in vivo and for biochemical and genetic markers of methicillin resistance. In vivo, nafcillin was equally effective against experimental aortic valve endocarditis in rabbits, regardless of whether they were infected by a fully susceptible or a low-level-resistant strain. Resistance did not emerge during therapy. For the more resistant of the two low-level-resistant strains, methicillin was as effective as nafcillin. Nafcillin was ineffective against endocarditis caused by a truly methicillin-resistant strain, and resistance emerged on therapy. The low-level-resistant strains did not produce the low-affinity penicillin-binding protein 2a that is associated with methicillin resistance and did not contain DNA that hybridized with probes that recognized the methicillin resistance determinant. Low-level resistance in S. aureus is a phenomenon that is biochemically and genetically distinct from true methicillin resistance. These strains actually are susceptible to beta-lactam antibiotics. The clinical problem posed by these strains is not a therapeutic one but, instead, one of how to differentiate them from those that are truly methicillin resistant.

Animals↗
PubMed1983

Biotypes, serotypes and phage types of caprine strains of Staphylococcus aureus.

Nine of 11 caprine strains of Staphylococcus aureus examined belong to biotype C. They were typable serologically using antisera developed for typing human strains of Staphylococcus aureus. H2 was found to be the dominant thermostable antigen whilst 1 and 0 were the most common thermolabile antigens. Some strains possessed protein A and poly A beta (beta-glucosaminyl ribitol teichoic acid). Phage typing of the strains was achieved with an international set of phages for typing human strains of Staphylococcus aureus and they belong to phage groups II, and the mixed group.

Animals↗
PubMed1982

Binding of retrovirus-associated protein kinase and proteins to Staphylococcus aureus.

Formalin-fixed Staphylococcus aureus strain Cowan, bearing protein A, routinely used for the absorption of antigen-antibody complexes, was found to bind protein kinase activity from disrupted Moloney murine leukaemia virus (Mo-MuLV). The Wood strain of S. aureus lacking protein A also bound the kinase with similar efficiency. About 50% of the bound kinase activity, as detected by phosphorylation of casein using [gamma-32P]ATP, could be eluted from the bacterial preparation with buffer containing 0 X 5 M-KC1. Similar results were obtained with Moloney murine sarcoma virus (Mo-MuSV) strain 349 and ts110 MuSV(MuLV). The bacterial preparation was also found to bind casein kinase activity from cellular extracts of uninfected, Rauscher murine leukaemia virus (R-MuLV)-infected and Mo-MuLV-infected cells. Analysis of [3H]leucine-labelled proteins from purified virus showed selective binding to S. aureus of only two major labelled virus proteins. One virus component bound to S. aureus had the relative mobility of p15; the other polypeptide co-migrated with virus p10. Upon exposure to increased salt concentration, most of the p10 but very little of the p15 proteins were released. The S. aureus-binding proteins from ts110 Mo-MuSV and MuSV-349 revealed similar binding and elution patterns of p10 and p15 molecules. The p10 and protein kinase activity eluted from Mo-MuLV-absorbed bacteria were separated by gel filtration into a high molecular weight species, containing p10 and kinase activity, and a low molecular weight p10 monomer lacking enzymic activity.

Casein Kinases↗
PubMed1982

Antibiotic-associated diarrhoea and methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus was thought to be the cause of 10 cases of antibiotic-associated diarrhoea observed over a 12-month period at The Royal Melbourne Hospital. Each patient had significant underlying disease, and all had been treated with multiple, broad-spectrum antibiotic agents. The diagnosis was made on the distinctive Gram-stain appearance of faecal smears, the heavy predominant growth of methicillin-resistant Staph. aureus from stool cultures, and the absence of other bowel pathogens, including toxigenic Clostridium difficile. Diarrhoea usually responded to treatment with vancomycin or bacitracin, and, in patients whose condition improved, the stools cleared of staphylococci. Patients with staphylococcal diarrhoea present a significant crossinfection risk, and early diagnosis, treatment, and isolation are essential.

Adult↗
PubMed1992

Substrate specificity and energetics of antiseptic and disinfectant resistance in Staphylococcus aureus.

Clinical isolates of Staphylococcus aureus carry various antiseptic and disinfectant resistance determinants (qac genes) on a variety of plasmids. The biochemistry and specificity of these resistance genes in S. aureus is the subject of this report. The qac genes were separated into two families on the basis of resistance profiles and DNA homology. Isotopic and fluorimetric assays demonstrated that the qac genes encode efflux systems that rely on proton motive force.

Anti-Infective Agents, Local↗