Staphylococcus aureus is a potentially pathogenic bacterium that causes a broad spectrum of diseases. S. aureus can adapt rapidly to the selective pressure of antibiotics, and this has resulted in the emergence and spread of methicillin-resistant S. aureus (MRSA). Resistance to methicillin and other beta-lactam antibiotics is caused by the mecA gene, which is situated on a mobile genetic element, the Staphylococcal Cassette Chromosome mec (SCCmec). To date, five SCCmec types (I-V) have been distinguished, and several variants of these SCCmec types have been described. All SCCmec elements carry genes for resistance to beta-lactam antibiotics, as well as genes for the regulation of expression of mecA. Additionally, SCCmec types II and III carry non-beta-lactam antibiotic resistance genes on integrated plasmids and a transposon. The epidemiology of MRSA has been investigated by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), spa typing and SCCmec typing. Numerous MRSA clones have emerged and disseminated worldwide. SCCmec has been acquired on at least 20 occasions by different lineages of methicillin-sensitive S. aureus. Although most MRSA strains are hospital-acquired (HA-MRSA), community-acquired MRSA (CA-MRSA) strains have now been recognised. CA-MRSA is both phenotypically and genotypically different from HA-MRSA. CA-MRSA harbours SCCmec types IV or V, and is associated with the genes encoding Panton-Valentine leukocidin. The prevalence of MRSA ranges from 0.6% in The Netherlands to 66.8% in Japan. This review describes the latest developments in knowledge concerning the structure of SCCmec, the molecular evolution of MRSA, the methods used to investigate the epidemiology of MRSA, and the risk-factors associated with CA-MRSA and HA-MRSA.

European Commission, 7th Framework Programme(grant agreement 223083).

No abstract

Background— Abdominal aortic aneurysms (AAA) are characterized by extensive transmural inflammation and C-reactive protein (CRP) has emerged as an independent risk factor for the development of cardiovascular disease. Therefore, we evaluated a possible association between serum CRP and aneurysm dimension in patients with asymptomatic AAA. Furthermore, the possibility of CRP production by aneurysmal tissue has been examined. Methods and Results— Serum CRP was determined highly sensitive ( hs CRP) and aneurysmal size was measured in 39 patients with AAA. The presence of CRP mRNA was assessed in the aneurysmal tissue of 16 patients. Mean (SD) hs CRP was 3.23 (2.96) mg/L. After log-transformation, hs CRP correlated significantly with aneurysmal size ( r =0.477, P =0.002). When the patients were divided into 3 equally sized groups according to hs CRP level, aortic diameter increased from lowest to upper hs CRP-tertile (49 mm, 61 mm, and 67 mm, respectively; P <0.05 for 3rd versus 1st tertile). This association persisted after correction for risk factors. CRP mRNA was found in 25% of aneurysmal aortic tissues. Conclusions— This is the first report showing that serum hs CRP is associated with aneurysmal size and that—in at least some patients—CRP may be produced by aneurysmal tissue. These data underscore the inflammatory nature of AAA formation, suggesting that serum hs CRP may serve as a marker of AAA disease and that CRP produced in vascular tissue might contribute to aneurysm formation.

The findings indicate that the mental state of angioplasty patients is positively associated with serological markers of inflammation. It remains to be seen whether the inflammation causes feelings of exhaustion, whether exhaustion and depression set the stage for inflammation, or whether existing feelings of exhaustion are amplified by the inflammation.

We have determined the complete genome sequence of the Maastricht strain of rat cytomegalovirus (RCMV). The RCMV genome has a length of 229,896 bp and is arranged as a single unique sequence flanked by 504-bp terminal direct repeats. RCMV was found to have counterparts of all but one of the open reading frames (ORFs) that are conserved between murine CMV (MCMV) and human CMV (HCMV). Like HCMV, RCMV lacks homologs of the genes belonging to the MCMV m02 glycoprotein gene family. However, RCMV contains 15 ORFs with homology to members of the MCMV m145 glycoprotein gene family. Four ORFs are predicted to encode homologs of host proteins; R33 and R78 both putatively encode G protein-coupled receptors, whereas r144 and r131 encode homologs of major histocompatibility class I heavy chains and CC chemokines, respectively. An intriguing feature of the RCMV genome is the presence of an ORF, r127, with similarity to the rep gene of parvoviruses as well as ORF U94 of human herpesvirus 6A (HHV-6A) and HHV-6B. Counterparts of these ORFs have not been found in the other sequenced herpesviruses.As a model for cytomegalovirus (CMV) infection and disease, we study the interaction between rat CMV (RCMV) and its host. The RCMV-rat model is attractive, since the pathogenesis of infection in RCMV-infected rats is similar to that in human CMV (HCMV)-infected humans. To fully exploit the RCMV-rat model, it is important to have a detailed picture of the genomic organization of RCMV. In this report, we present the complete DNA sequence of the RCMV (Maastricht) genome. Following HCMV (11) and murine CMV (MCMV) (37), RCMV is the third CMV for which the complete genome sequence has been determined. In addition, the RCMV genome represents the first complete sequence of a rat-specific herpesvirus.General features of the RCMV genome sequence. The RCMV genome was sequenced in a directed fashion, by using the previously cloned EcoRI and XbaI genomic subclones (32) as starting points. Overlapping plasmid clones of the genome were generated by using various restriction endonucleases. Both strands of each plasmid insert were sequenced by the dideoxynucleotide chain termination method. The final sequence was determined on both strands over 100% of the RCMV genome. Sequence assembly and analysis was done with the program PC/Gene (version 2.11; IntelliGenetics, Mountain View, Calif.) and with software from the United Kingdom human genome mapping project resource center (Hinxton, Cambridge, United Kingdom [http://www.hgmp .mrc.ac.uk]).The length of the RCMV (Maastricht) genome was found to measure 229,896 bp, which is approximately 6 kb larger than a previous estimate that was based on an analysis of viral genomic restriction fragments (32). Remarkably, the genome of RCMV is only 382 bp shorter than that of MCMV (Smith) (37). The RCMV genome has an overall GϩC content of 61% and consists of a single unique sequence flanked by 504-bp direct terminal repeats (TRs). The TRs are highly GϩC rich (76%) and not represented elsewhere in the genome. Within the ...

Cytomegalovirus (CMV) infections have been shown to dramatically affect solid organ transplant graft survival in both human and animal models. Recently, it was demonstrated that rat CMV (RCMV) infection accelerates the development of transplant vascular sclerosis (TVS) in both rat heart and small bowel graft transplants. However, the mechanisms involved in this process are still unclear. In the present study, we determined the kinetics of RCMV-accelerated TVS in a rat heart transplant model. Acute RCMV infection enhances the development of TVS in rat heart allografts, and this process is initiated between 21 and 24 days posttransplantation. The virus is consistently detected in the heart grafts from day 7 until day 35 posttransplantation but is rarely found at the time of graft rejection (day 45 posttransplantation). Grafts from RCMV-infected recipients had upregulation of chemokine expression compared to uninfected controls, and the timing of this increased expression paralleled that of RCMV-accelerated neointimal formation. In addition, graft vessels from RCMV-infected grafts demonstrate the increased infiltration of T cells and macrophages during periods of highest chemokine expression. These results suggest that CMV-induced acceleration of TVS involves the increased graft vascular infiltration of inflammatory cells through enhanced chemokine expression.With the escalation in the number of immunosuppressed patients undergoing immunosuppressive therapy following solid organ or bone marrow transplantation, human cytomegalovirus (HCMV) disease has now become a major clinical problem. While the majority of HCMV infections result in subclinical disease in healthy individuals, HCMV is a significant pathogen in immunocompromised patients (1,3,4,9,26,33,34,50,51,56). Primary HCMV infection is followed by lifelong persistence of the virus in a latent state, and reactivation of the latent virus is considered to be the major source of virus in these immunocompromised individuals. HCMV has been linked to the development of atherosclerosis, arterial restenosis following angioplasty, and solid organ transplant vascular sclerosis (TVS) (26)(27)(28)47). HCMV infection doubles the 5-and 3-year rates of graft failure due to accelerated TVS in cardiac and liver transplant patients, respectively (15; L. W. Miller, Editorial, J. Heart Lung Transplant. 11:S1-S4, 1992). The observation that HCMV infects many of the cell types involved in vascular disease, including monocyte-derived macrophages, endothelial cells, and smooth muscle cells (SMC), suggests that HCMV may play a role in these disease processes. Because of the similarities between the CMV-speciesspecific viruses, animal models provide an ideal tool to study the association between CMV and TVS.The most compelling evidence that herpesviruses play a role in vascular disease comes from studies in animal models. Using a rat CMV (RCMV) solid organ transplant model, researchers have demonstrated, in light of the RCMV-associated acceleration of TVS, an association of herpesvirus ...

Epstein-Barr virus (EBV) infection is associated with many lymphoproliferative diseases, such as infectious mononucleosis andBurkitt's lymphoma. Consequently, EBV is one of the most extensively studied herpesviruses. Surprisingly, a putative G protein-coupled receptor (GPCR) gene of EBV, BILF1, has hitherto escaped attention, yet BILF1-like genes are conserved among all known lymphocryptovirus species, suggesting that they play a pivotal role in viral infection. To determine the function of EBV BILF1, the activity of this gene and its products was studied. BILF1-specific mRNA was detected in various EBV-positive cell types and found to be expressed predominantly during the immediate early and early phases of infection in vitro. Interestingly, in COS-7 cells transfected with BILF1 expression constructs, a decrease in forskolin-induced CRE-mediated transcription was measured, as well as an increase in NF-B-mediated transcription. In contrast, CREmediated transcription was increased in EBV-positive Burkitt's lymphoma cells as well as EBV-positive lymphoblastoid B cells transfected with BILF1, whereas NF-B-mediated transcription levels remained unaffected in these cells. All observed activities were sensitive to treatment with pertussis toxin, indicating that the BILF1-encoded protein mediates these activities by coupling to G proteins of the G i/o class. Finally, reduced levels of phosphorylated RNA-dependent antiviral protein kinase were observed in COS-7 and Burkitt's lymphoma cells transfected with BILF1. Neither of the observed effects required a ligand to interact with the BILF1 gene product, suggesting that BILF1 encodes a constitutively active GPCR capable of modulating various intracellular signaling pathways.