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Since 1998, an increasing number of meticillin-resistant Staphylococcus aureus (MRSA) isolates with one of two characteristic phage patterns have been referred to the authors' laboratory from Northern Ireland. These strains were designated 'Irish-1' and 'Irish-2'. Analysis of 956 submitted isolates classified as Irish-1 or Irish-2 showed that 97% of the former and 95% of the latter were from Northern Ireland. Only 0.2% and 3%, respectively, were from England. Eleven Irish-2 isolates had been referred from Western Australia as representatives of an epidemic strain originally isolated there in 1994. Ninety isolates with the Irish-1 phage pattern and 91 isolates with the Irish-2 phage pattern, from numerous hospitals, were characterized by SmaI pulsed-field gel electrophoresis (PFGE), toxin gene carriage and antibiotic susceptibility. PFGE showed that, within each collection, a few isolates represented unrelated strains, but the majority were within six band differences of the most common profiles. Half of the Irish-1 isolates were homogeneous, with 22 DNA profiles among the remainder. Irish-2 isolates had two common profiles, D1 and D2, equally divided between one-third of the isolates and differing from each other by two bands; the remaining isolates shared 31 DNA profiles. Cluster analysis showed some overlap in DNA profiles between the Irish-1 and Irish-2 strains, but clear separation from other epidemic MRSA strains. There was no obvious correlation between PFGE profile and either antibiotic resistance pattern or toxin gene possession. All but three Irish-1 isolates possessed only the staphylococcal enterotoxin A (sea) gene, whereas almost all Irish-2 isolates were negative for all 12 enterotoxin genes. Sixty-nine percent of Irish-2 isolates were resistant to ciprofloxacin, erythromycin, kanamycin, neomycin and streptomycin, while 90% of Irish-1 isolates were resistant to all these plus gentamicin and mupirocin. All isolates were sensitive to quinupristin/dalfopristin, teicoplanin and vancomycin. Urease production was negative in both strains. The results suggest that Irish-1 and Irish-2 are distinct epidemic strains, identifiable by phage typing, DNA profiles, antibiotic resistance and toxin gene carriage.
ink: Molecular nature
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) with Panton-Valentine leukocidin (PVL) genes is increasing worldwide. Nosocomial outbreak-derived (hospital-acquired) MRSA (HA-MRSA) in Japan in the 1980s was also largely PVL( ). PVL( ) HA-MRSA and CA-MRSA shared the same multi-locus sequence type (ST30) and methicillin resistance cassette (SCCmecIV), but were divergent in oxacillin resistance, spa typing, PFGE analysis or clfA gene analysis. PVL( ) HA-MRSA, which probably originated in PVL( )S. aureus ST30, was highly adhesive (carrying cna and bbp genes), highly-toxic (carrying luk(PV) and sea genes) and highly drug-resistant. PVL( ) HA-MRSA was once replaced by other PVL(-) HA-MRSA (e.g., ST5), and is re-emerging as CA-MRSA.
Link: Journal of Medical Microbiology.
MRSA-infected nondiabetic and diabetic mice died on 19�1�1�4 and 10�6�0�7 days post-infection (p.i.), respectively. MRSA and MSSA infection in diabetic mice did not result in symptomatic bacteraemia; however, MRSA infection in diabetic mice significantly reduced glucose levels (P<0�05). Diabetic mice showed significantly higher levels of C-reactive protein, fibrinogen, fibronectin and von Willebrand factor than nondiabetic mice (P<0�05), and MRSA infection further elevated the plasma levels of these inflammatory and endothelial markers (P<0�05). Before infection, diabetic mice had significantly higher plasminogen activator inhibitor-1 (PAI-1) activity, lower antithrombin III (AT-III) and protein C activities (P<0�05), and MRSA infection significantly increased PAI-1 activity further and reduced the activity of AT-III and protein C (P<0�05). MRSA infection increased the production of three Th1 cytokines, interleukin 2 (IL-2), tumour necrosis factor alpha and gamma interferon, in diabetic mice (P<0�05); however, three Th2 cytokines, IL-4, IL-6, IL-10, were elevated at 2 and 4 days p.i., and then dropped gradually. MRSA infection in diabetic mice accelerated the inflammation process, endothelial injury and blood coagulation in diabetic mice. Therefore, the development of proper infection diagnosis and timely use of effective treatments for MRSA-infected diabetic individuals is important and necessary.
Link: Journal of Clinical Microbiology.
The sdr locus was found in all 497 investigated Staphylococcus aureus strains, although in 29 strains it contained only the sdrC gene (sdrD negative, sdrE negative). The sdrC-positive, sdrD-negative, sdrE-negative gene profile was exclusive to methicillin-sensitive S. aureus (MSSA) strains (Fisher's exact test; P = 0.0005) and was not found in the strains collected from bone infections (P = 0.0019). We also found a strong association between the presence of the sdrD gene and methicillin-resistant S. aureus strains (P < 0.0001). Our findings suggest that MSSA strains with the newly uncovered sdrC-positive, sdrD-negative, sdrE-negative gene profile have a substantially decreased potential to establish bone infection.
Link: Journal of Clinical Microbiology.
Clusters obtained with microarrays showed a high degree of similarity with those obtained by pulsed-field gel electrophoresis or variable number of tandem repeats. Clusters clearly segregated hospital-onset strains from community-onset strains. Moreover, the microarray approach allowed definition of novel marker genes and chromosomal regions specific for given groups of isolates, thus providing better discrimination and additional information compared to pulsed-field gel electrophoresis and variable number of tandem repeats. Finally, the comparative genome hybridization approach unraveled the occurrence of multiple horizontal transfer events leading to community-onset MRSA as well as the need for a specific genetic background in recipient strains for both the acquisition and the stability of the mec element.
Link: Journal of Clinical Microbiology.
Methicillin-resistant Staphylococcus aureus (MRSA) clones harboring the toxic shock syndrome toxin 1 (tst) gene have been detected in France and in Switzerland since 2002. During a passive survey conducted between 2002 and 2003, we collected 103 tst-positive S. aureus isolates from 42 towns in France, of which 27 were resistant to methicillin. The tst-positive MRSA belonged to two clones: a major clone comprising 25 isolates of sequence type (ST) 5 and agr group 2 and a minor clone comprising two isolates of ST30 and agr3. The tst-positive MRSA clones were associated with both hospital-acquired (12 cases) and community-acquired (8 cases) infections. The MRSA clones were mainly isolated from children (overall median age, 3 years). They caused a variety of clinical syndromes, including toxic shock syndrome and suppurative infections. Both clones were found to harbor a type IV staphylococcal chromosomal cassette mec (SCCmec) and to have similar antibiotic resistance profiles (usually resistant to oxacillin, kanamycin, and tobramycin and with intermediate resistance to fusidic acid). The origin of these clones is unclear. The tst-positive agr2 MRSA clone has the same sequence type (ST5) of two pandemic nosocomial MRSA clones, namely, the Pediatric clone and the New York/Japan clone. These findings suggest that all these clones are phylogenetically related. The pulsotype of the tst-positive MRSA clones differed from that of methicillin-sensitive S. aureus (MSSA) clones by a single band involving the SCCmec element. These findings suggest that the tst-positive MRSA clones may have emerged from their respective MSSA counterparts.
Link: ABC News
Researchers have succeeded in deciphering the genetic make-up of a major strain of drug-resistant, potentially deadly staph bacteria in the United States. Genes responsible for the virulence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) in this country appear to be taken from another, less toxic, bacterium. "It has, in effect, borrowed genetic characteristics from an otherwise rather benign organism and, in so doing, acquired an extra degree of lethality," explained Dr. Pascal James Imperato, chairman of the department of preventive medicine and community health and director of the master of public health program at the State University of New York Downstate Medical Center in New York City. Imperato was not involved in the study, which appears in the Feb. 29 online issue of The Lancet. The newly mapped genes could be used as markers to track the spread of this particular strain in both hospital and community settings, and to investigate more effective therapies to fight it
Link: HighWire Press
Pulsed-field gel electrophoresis (PFGE) is currently the gold standard for methicillin-resistant Staphylococcus aureus (MRSA) typing but only one enzyme, SmaI, is currently used for restriction digest. We report the use of virtual digestion to identify enzymes for S. aureus PFGE. Two enzymes (EagI and SacII) were identified and successfully used to characterize two sets of S. aureus isolates, 12 USA300, and 14 additional MRSA isolates comprised of seven SmaI patterns. Phylogenetic analysis of patterns generated by all enzymes determined that the USA300 MRSAs are identical. In contrast, digestion with EagI or SacII resolved one to two band differences among three MRSA pattern sets that were not detected using SmaI. These results demonstrate that a second enzyme may detect differences in S. aureus isolates not detected by single enzyme digestion. However, because isolates differing by one to two bands are considered identical, such discrimination may not be clinically or epidemiologically relevant.
Link: Biofilm Formation
The association between biofilm formation and the accessory gene regulator (agr) types of methicillin-resistant Staphylococcus aureus (MRSA) strains in our hospital were investigated. The biofilm index and the incidence of MRSA strains carrying agr-2 in the infection group (n=91) were significantly higher than were those in the carrier group (n=225), suggesting that biofilm formation and agr type are associated with nosocomial MRSA infections.
Link: Methicillin-Resistant
We describe 279 hospitalized Canadian aboriginals in whom methicillin-resistant Staphylococcus aureus (MRSA) was detected. They were identified in 38 Canadian hospitals from 1995 through 2002. Compared with nonaboriginals, aboriginals were more likely to be younger than 18 years of age (OR, 1.8; P<.0001), to have had an MRSA infection (OR, 3.8; P<.0001), and to have had MRSA isolated from specimens of skin or soft tissue (OR, 4.1; P=.016). The clinical features of MRSA infection in aboriginals are distinct from those in the general patient population with MRSA infection in Canadian hospitals, and the genetic background of MRSA isolates from aboriginals also varies from that of strains from the non-aboriginal population.
Link: Journal of Medical Microbiology
Sixty-three Staphylococcus aureus strains (40 from clinical sources and 23 from food sources) were examined for toxic shock syndrome toxin-1 (TSST-1) using PCR, phage typed using the international phage set (IPS) and tested for their susceptibility to antibiotics. Only three strains (all from clinical sources) were positive for the TSST-1 gene (tst). The majority of S. aureus strains that were typeable by IPS belonged to group II. Resistance to one or more antibiotics was detected in 47�5 and 73�9 % of clinical and food strains, respectively. This is the first time that PCR detection of tst in S. aureus has been reported from Libya, and further studies are needed on the occurrence of toxic shock syndrome in the community and the role of TSST-1-producing S. aureus in this disease in Libya.
Link: Infection and Immunity
Small colony variants (SCVs) of Staphylococcus aureus are slow-growing morphological variants that have been implicated in persistent, relapsing, and antibiotic-resistant infections. The altered phenotype of SCVs in most strains has been attributed to defects in electron transport due to mutations in hemin or menadione biosynthesis. The pathogenic capacity of SCVs compared to phenotypically normal strains is variable depending on the attribute examined, with some studies showing reduced virulence of SCVs and others demonstrating normal or heightened virulence. Recently, the nematode Caenorhabditis elegans has been successfully employed as an alternative host to investigate virulence mechanisms of a variety of bacterial pathogens, including S. aureus. In this study, we show that clinical SCVs as well as hemB- and menD-deficient mutants of S. aureus are greatly reduced in virulence in the C. elegans infection model.
Link: HighWire Press -- Medline Abstract.
The aim of this study was to identify a set of genetic polymorphisms that efficiently divides methicillin-resistant Staphylococcus aureus (MRSA) strains into groups consistent with the population structure. The rationale was that such polymorphisms could underpin rapid real-time PCR or low-density array-based methods for monitoring MRSA dissemination in a cost-effective manner. Previously, the authors devised a computerized method for identifying sets of single nucleotide polymorphisms (SNPs) with high resolving power that are defined by multilocus sequence typing (MLST) databases, and also developed a real-time PCR method for interrogating a seven-member SNP set for genotyping S. aureus. Here, it is shown that these seven SNPs efficiently resolve the major MRSA lineages and define 27 genotypes. The SNP-based genotypes are consistent with the MRSA population structure as defined by eBURST analysis. The capacity of binary markers to improve resolution was tested using 107 diverse MRSA isolates of Australian origin that encompass nine SNP-based genotypes. The addition of the virulence-associated genes cna, pvl and bbp/sdrE, and the integrated plasmids pT181, pI258 and pUB110, resolved the nine SNP-based genotypes into 21 combinatorial genotypes. Subtyping of the SCCmec locus revealed new SCCmec types and increased the number of combinatorial genotypes to 24. It was concluded that these polymorphisms provide a facile means of assigning MRSA isolates into well-recognized lineages.
Link: The Journal of Bacteriology.
Staphylococcus aureus is the most common cause of hospital-acquired infection. In healthy hosts outside of the health care setting, S. aureus is a frequent colonizer of the human nose but rarely causes severe invasive infection such as bacteremia, endocarditis, or osteomyelitis. To identify genes associated with community-acquired invasive isolates, regions of genomic variability, and the S. aureus population structure, we compared 61 community-acquired invasive isolates of S. aureus and 100 nasal carriage isolates from healthy donors using a microarray spotted with PCR products representing every gene from the seven S. aureus sequencing projects. The core genes common to all strains were identified, and 10 dominant lineages of S. aureus were clearly discriminated. Each lineage carried a unique combination of hundreds of "core variable" (CV) genes scattered throughout the chromosome, suggesting a common ancestor but early evolutionary divergence. Many CV genes are regulators of virulence genes or known or predicted to be expressed on the bacterial surface and to interact with the host during nasal colonization and infection. Within each lineage, isolates showed substantial variation in the carriage of mobile genetic elements and their associated virulence and resistance genes, indicating frequent horizontal transfer. However, we were unable to identify any association between lineage or gene and invasive isolates. We suggest that the S. aureus gene combinations necessary for invasive disease may also be necessary for nasal colonization and that community-acquired invasive disease is strongly dependent on host factors.
Link: HighWire Press -- Medline Abstract.
OBJECTIVES: The emergence of antibiotic-resistant bacteria such as Staphylococcus aureus calls for inventive research and development strategies. Inhibition of bacterial pathogenesis may be a promising therapeutic approach in this regard. The gene-silencing effect of short interfering RNA (siRNA) is useful for this strategy. We investigated the efficacy of siRNA on the expression of coagulase because it is the one of the most important enzymes in the pathogenesis of methicillin-resistant S. aureus (MRSA) infection. METHODS: We designed and synthesized 21 bp siRNA duplexes against staphylococcal coagulase. RT-PCR was performed to determine whether the siRNAs inhibit the expression of the coagulase mRNA and radiolabelled siRNA was used to confirm transfection to bacteria in vitro. The efficacy of siRNA was determined in a murine model of haematogenous pulmonary infection. RESULTS: RT-PCR showed that siRNAs significantly inhibited the expression of the coagulase mRNA. The coagulase titres in the siRNA and control groups were 8 and 32, respectively. Measurement of incorporated radioactivity indicated that the siRNAs were delivered into the bacteria. In the murine infection model, in control and siRNA groups, 7.64 /- 0.42 and 6.29 /- 0.23 log cfu/mL (mean /- SEM) MRSA were detected, respectively, showing that there was a significant decrease in the number of viable bacteria in the siRNA group (P < 0.05). CONCLUSIONS: The results show that siRNA inhibited both mRNA expression and the activity of MRSA coagulase in vitro. The in vivo results revealed that the siRNA was effective in reducing the bacterial load in a murine model of haematogenous pulmonary infection. Targeting of coagulase with siRNA appears to be a novel strategy for treating MRSA infections.
Link: The Journal of Bacteriology.
The evolution of Staphylococcus aureus has been described as predominantly clonal, based on evidence from seven housekeeping genes. We aimed to test if this was also true for more polymorphic genes. In a collection of 60 isolates including major European epidemic methicillin-resistant S. aureus (MRSA) and sporadic MRSA strains, we compared the partial gene sequences of seven housekeeping genes (arcC, aroE, glpF, gmk, pta, tpi, and yqiL), six core adhesion genes (present in all strains) (clfA, clfB, fnbA, map, sdrC, and spa), and four accessory adhesion genes (not present in all strains) (ebpS, fnbB, sdrD, and sdrE). Nucleotide diversity of adhesion genes was 2- to 10-fold higher than genes used for multilocus sequence typing. All genes showed evidence for purifying selection with a weakly reduced level among accessory adhesion genes. Among these highly variable genes, there was no evidence for a difference in molecular evolution between epidemic and sporadic strains. Gene trees constructed from concatenated sequences of housekeeping, core adhesion, and accessory adhesion genes were highly congruent, indicating clonality, despite some evidence for homologous exchange. Further evidence for clonality was found with an overall positive correlation of allelic and nucleotidic divergence for both seven housekeeping genes and six core adhesion genes. However, for small allelic differences that fit the demarcations of clonal complexes (CCs) there was no such correlation, suggesting that recombination occurred. Therefore, despite an overall clonal population structure, recombination between related isolates within CCs might have contributed to S. aureus evolution.
Link: The Journal of Bacteriology.
The accessory gene regulator (agr) locus influences the expression of many virulence genes in the human pathogen Staphylococcus aureus. Four allelic groups of agr, which generally inhibit the regulatory activity of each other, have been identified within the species. Interference in virulence gene expression caused by different agr groups has been suggested to be a mechanism for isolating bacterial populations and a fundamental basis for subdividing the species. To test the hypothesis that the species is phylogenetically structured according to agr groups, we mapped agr groups onto a clone phylogeny inferred from partial sequences of 14 genes from 27 genetically diverse strains. Shimodaira-Hasegawa and parametric bootstrap tests rejected the hypotheses that the species is subdivided into three or five monophyletic agr groups but failed to reject the hypothesis that the species is subdivided into two groups that each consist of multiple clonal complexes and multiple agr groups. Additional evidence for agr recombination is found from clustered polymorphisms in complete agr sequences. However, agr recombination has not occurred frequently or randomly through time, because the topology and branch lengths of the clone phylogeny are reflected within each agr group. To account for these observations, we propose a new evolutionary model that involves a genetically polymorphic ancestral population of S. aureus that horizontally transferred agr groups between two subspecies groups near the time that these subspecies groups diverged.
Link: JAMA
A new study by scientists from the National Institute of Allergy and Infectious Diseases and colleagues describes how community-acquired methicillin-resistant Staphylococcus aureus (MRSA) may evade the host immune response (Voyich et al. J Immunol. 2005;175:3907-3919). MRSA bacterial strains are difficult to treat and are becoming more prevalent over time. Compared with hospital strains, community-acquired strains often cause more serious infections in otherwise healthy individuals. Through mouse experiments and DNA microarray analyses, the researchers identified specific S aureus genes that potentially control the bacterium’s escape from neutrophils, the body’s first line of defense against bacteria. Identifying which genes help bacteria evade and destroy neutrophils and determining how they do so could lead to new medical treatments.
Link: Genetic Differentiation
In spite of these common features in MRSA strains from Korea and Japan, we also observed some genotypic divergence in MRSA from the two countries. Several spa types might be differentiated from a prevalent prototype (TJMBMDMGMK) that is shared by the two countries, revealing a unique geographic distribution. SCCmec type II lacking pUB110, designated type IIA, was found more frequently in Korea than in Japan. The rate of gentamicin resistance was also dramatically different between the two countries: 87.2% (Korea) vs. 28.6% (Japan). These preliminary findings suggested that MRSA strains from Korea and Japan might have originated from a common ancestor, but then clearly differentiated according to locality. A further comprehensive study should be performed to document the hypotheses from this study.
Link: The Journal of Bacteriology.
We present evidence, using a newly developed, luciferase-based agr typing scheme, that the evolutionary divergence of the agr system was an early event in the evolution of the staphylococci and long preceded the development of the nucleotide polymorphisms presently used for genotyping. These polymorphisms developed, for the most part, within different agr groups; mobile genetic elements appear also to have diffused recently and, with a few notable exceptions, have come to reside largely indiscriminately within the several agr groups.
Link: CytoGenix, Inc.
Over the past two years, CytoGenix scientists have conducted numerous studies showing that DNA compounds are effective against bacterial pathogens including E. coli and resistant strains of Staphylococcus aureus (MRSA). These studies have led to discoveries of unique compounds and DNA sequences that regulate crucial bacterial proteins. Life-threatening infections by newly evolving strains of resistant Staph are becoming a significant public health problem. The Centers for Disease Control and Prevention reports, "Staph bacteria are one of the most common causes of skin infection in the United States, and are a common cause of pneumonia and bloodstream infections...as many as 100,000 persons are hospitalized each year with MRSA infections, although only a small proportion of these persons have disease onset occurring in the community." The nation's annual cost associated with sepsis care is approximately $16.7 billion, and the average length of hospital stay is 19.6 days per patient. The incidence of sepsis is likely to increase because of an aging population and the widespread use of broad-spectrum antibiotics that cause pathogens to mutate and become resistant.
Link: HighWire Press -- Medline Abstract.
If you're a genticist you'll love this!
The post-methicillin resistant Staphlylococcus aureus (MRSA) infection nephritis is a progressive glomerulonephritis that occurs following Staphylococcus aureus infection. It has been assumed that staphylococcal superantigens and other cellular antigens are necessary for the development of post-MRSA infection nephritis, and we have previously identified a staphylococcal cell membrane antigen (GenBank, accession number; BAB41819.1) as a possible antigen in post-MRSA infection nephritis.
A chemical which gives the bacterium responsible for MRSA its characteristic golden pigment helps it ward off the human immune system, US scientists say. They believe the molecule neutralises chemicals the human body releases to destroy the staphylococcus bacterium. The University of California team says targeting this molecule could offer ways to stop antibiotic-resistant forms of the bug, including MRSA. The study is reported in the Journal of Experimental Medicine.
Link: Journal of Clinical Microbiology.
Seventy-one percent of 76 methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from two medical centers in El Paso, Texas, represent three similar pulsed-field gel electrophoresis types. Overall, six pulsed-field types were identified represented by multilocus sequence/staphylococcal chromosomal cassette DNA mec (SCCmec) types: ST5-MRSA-II; ST36-MRSA-II; ST8 (untypeable SCCmec); and a newly described clonal cluster 8 strain, ST507-MRSA-IV. This study demonstrates the presence of multiple-antibiotic-resistant epidemic MRSA clones in El Paso.
Link: The Journal of Bacteriology.
Staphylocoagulase detection is the hallmark of a Staphylococcus aureus infection. Ten different serotypes of staphylocoagulases have been reported to date. We determined the nucleotide sequences of seven staphylocoagulase genes (coa) and their surrounding regions to compare structures of all 10 staphylocoagulase serotypes, and we inferred their derivations.
Link: Genetic Background Affects Stability of mecA in Staphylococcus aureus..
The staphylococcal methicillin resistance determinant, mecA, resides on a mobile genetic element, staphylococcus chromosomal cassette mec (SCCmec). The distribution of SCCmec in nature is limited to relatively few clonal complexes of related methicillin-resistant Staphylococcus aureus (MRSA). We have previously reported that some genetic backgrounds are restrictive of mecA and penicillin-binding protein 2a expression, which could account for the restricted clonal distribution of SCCmec in nature. In this study, we investigate the potential role of the host chromosome in the transformability and expression of mecA in 103 naturally occurring methicillin-susceptible S. aureus clinical isolates. The isolates, which had been genotyped previously by multilocus sequence typing, were classified into one of two mutually exclusive categories based on whether the isolates belonged to "major" MRSA lineages or to "other" lineages that are never or occasionally MRSA. We introduced mecA expressed on the low-copy-number plasmid pYK20 into each MSSA strain and assayed the phenotype of resistance to nafcillin by population analysis to assess the relationship between the stability of mecA expression and genetic background. Strains from the major MRSA lineages were more transformable with pYK20 and better able to maintain the plasmid and express resistance in comparison to strains from other lineages. These data support the hypothesis that the presence of mecA within relatively few clonal complexes is partly due to genetic factors that are permissive of mecA and its gene product.
Link: Seven novel variants in MRSA genetics
Methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered in Irish hospitals between 1971 and 2002 were characterized using multilocus sequence typing (MLST) (n = 130) and SCCmec typing (n = 172). Where atypical SCCmec typing results were obtained, PCR amplification of entire SCCmec elements, analysis of amplimer mobility, and nucleotide sequencing were undertaken. MLST revealed that 129/130 isolates had the same genotypes as internationally spread MRSA clones, including ST239, ST247, ST250, ST5, ST22, ST36, and ST8. A novel genotype, ST496, was identified in one isolate. Half of the isolates (86/172) had SCCmec type I, IA, II, III, or IV. The remaining 86 isolates harbored novel SCCmec variants in three distinct genetic backgrounds: (i) 74/86 had genotype ST8 and either one of five novel SCCmec II (IIA, IIB, IIC, IID, and IIE) or one of two novel SCCmec IV (IVE and IVF) variants;........
Link: Susceptibility and resistance genes to fluoroquinolones in MRSA
The activity of six fluoroquinolones (FQs) was determined against 100 methicillin-resistant Staphylococcus aureus (MRSA) isolated in 2002 along with mutations in the grlA and gyrA genes and in the norA promoter of these isolates. Of the isolates tested, 97% had mutations in grlA and gyrA. A single mutation in grlA and gyrA resulted in a decrease of susceptibility to old generation FQs (norfloxacin, enoxacin, ciprofloxacin, fleroxacin, sparfloxacin and levofloxacin) but not to new generation FQs (gatifloxacin and moxifloxacin). Double mutations of both grlA and gyrA resulted in high-level resistance to all FQs tested. All norA mutants (15%) contained double mutations in grlA and gyrA and showed no decrease of MIC in the presence of reserpine, which is known to inhibit the drug-efflux pump. Our results showed that double mutations in grlA and gyrA were necessary for the expression of high-level resistance to new generation FQs. As different FQ-resistant mutants occur in the same PFGE type, FQ-resistant MRSA may well develop individually.
Link: Discovery .
The discovery of a 'molecular switch' could lead to new ways of treating infections such as MRSA, and inflammatory diseases like arthritis. According to research published today in Nature, the team from Imperial College London and the University of California, San Diego, have identified an enzyme called IKK, which can act as a 'brake' on an immune cell pathway responsible for regulating the body's response to infection and inflammation. By inhibiting IKK activity the researchers were able to increase the body's ability to fight off infection, but at the same time also increased the body's inflammatory response. They also found that IKKa inhibits activation of immune cells, and inhibits inflammation, a discovery which could lead to new ways of treating diseases such as arthritis. Dr Toby Lawrence, a Wellcome Trust International Research Fellow from Imperial College London, based at the Kennedy Institute of Rheumatology, and lead author of the research, says: "The identification of this 'double-edged sword' could be of huge importance in how we deal with a number of major health issues, including MRSA. With antibacterial resistance on the rise, this development could provide doctors with a new way to stop infections without resorting to a cocktail of antibiotics.
Link: Infection and Immunity.
Pls, a surface protein of certain methicillin-resistant Staphylococcus aureus strains, is associated with poor bacterial adherence to solid-phase fibronectin and immunoglobulin G, as well as with reduced invasion of cultured epithelial cells. Here the importance of Pls for the development of septic arthritis and sepsis was investigated by using a mouse model.
Link: this is nottingham
University of Nottingham scientists say they have taken a step forward in the fight against superbugs, such as MRSA. They have identified the structure of an important protein involved in the reproduction of bacteria, which they hope will enable drugs to be designed to prevent their growth. The research has involved a bacteria called Bacillus strearothermophilus, but researchers are confident that the same results would be seen in more harmful bacteria. In a scientific paper being published today, the researchers explain how they hope to be able to stop infection-causing bacteria at a molecular level. Leading the Nottingham team, Dr Panos Soultanas said: "Many, many strains of bacteria have already become resistant to drugs. To overcome this we need to find inventive ways of developing new treatments and we believe there is great potential in using molecules that will disrupt protein to protein interactions necessary for the replication of DNA in bacteria, essentially leaving them unable to reproduce. It's a race between us and the bugs and we always need to keep one step ahead to find new drugs."
Link: Bioinformatics.
We have identified a novel domain that we call the G5 domain (named after its conserved glycine residues), which is found in a variety of enzymes such as Streptococcal IgA peptidases and various glycosyl hydrolases in bacteria. The G5 domain is found in the Accumulation Associated Protein (AAP), which is an important component in biofilm formation in Staphylococcus aureus. A common feature of the proteins containing G5 domains is N-acetylglucosamine binding, and we attribute this function to the G5 domain.
Link: Journal of Clinical Microbiology.
Synthesis of a polysaccharide adhesin by icaADBC-encoded enzymes is currently the best-understood mechanism of staphylococcal biofilm development. In four methicillin-resistant Staphylococcus aureus isolates, environmental activation of icaADBC did not always correlate with increased biofilm production. Moreover, glucose-mediated biofilm development in these isolates was icaADBC independent. Apparently, an environmentally regulated, ica-independent mechanism(s) of biofilm development exists in S. aureus clinical isolates.
Link: Journal of Antimicrobial Chemotherapy.
Progress on rational intervention to prevent increasing antibiotic resistance has been slow. We suggest that this is because the science of resistance epidemiology has received little attention, and that a systematic, co-operative investigation of this area might yield a relevant knowledge base, analogous to the basis for effective public health intervention in infectious disease given by infection epidemiology. The steps required to progress this approach in the UK are discussed, along with a summary of what is known and speculation on what might emerge.
Link: - Antimicrobial Agents and Chemotherapy.
In conclusion, the data presented in this report provide evidence at the molecular level that the deleterious effects of fusidic acid resistance-mediating exchanges within EF-G of S. aureus can be reduced considerably by specific compensating mutations in this target protein. This compensatory adaptation most likely plays a significant role in the stabilization of resistant bacteria within a given population.
Link: NEWS.com.au | 27 patients hit by superbug (05-04-2005).
This story is about VRE. The concern in the MRSA community is that it might mutate with MRSA and speed up the process of vancomycin resistance and the growth of VRSA
AN antibiotic-resistant strain of bacteria has been detected in another 27 patients at one of Singapore's largest hospitals, bringing the total number of diagnosed cases to 42, health officials said. Of the 42 patients hit by the vancomycin-resistant enterococci (VRE) bacteria, only one is an infected patient while the rest are carriers, the Singapore General Hospital said late Monday. The hospital first reported last Friday 15 patients were diagnosed with the bacteria and saw a cluster of six VRE cases last year. Advertisement: According to a hospital spokeswoman, there have been no fatal cases of VRE and no medical treatment is required unless a patient has been infected with the bacteria. Patients infected by VRE may suffer infections of the urinary tract, bloodstream and surgical sites. To contain the spread of the bacteria, the hospital is continuing to screen all its inpatients for VRE, which is spread by touching infected areas or items contaminated by the bacteria.
Link: The Journal of Bacteriology.
The latter genes were evidently introduced by homologous recombination from distantly related genomes, and in many cases, the pattern of nucleotide substitution made it possible to reconstruct the most probable recombination event involved. These recombination events introduced genes encoding proteins that differed in amino acid sequence and thus potentially in function. Several of the proteins are known or likely to be involved in pathogenesis (e.g., staphylocoagulase, exotoxin, Ser-Asp fibrinogen-binding bone sialoprotein-binding protein, fibrinogen and keratin-10 binding surface-anchored protein, fibrinogen-binding protein ClfA, and enterotoxin P). Therefore, the results support the hypothesis that exchange of homologous genes among S. aureus genomes can play a role in the evolution of pathogenesis in this species.
Link: SGM : News : Media Releases.
Britain's MRSA epidemic may be due to the emergence of highly transmissible clones of the superbug, according to an article in the February 2005 issue of Microbiology Today, the quarterly magazine of the Society for General Microbiology. Studies by Dr Mark Enright at the University of Bath have shown that the increase in the number of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK coincided with the appearance and dominance of two clones, called UK Epidemic MRSA clone-15 and clone-16. "These clones appear to be highly transmissible compared to other MRSA clones, allowing them to easily spread from patient to patient," explains Dr Enright. "They are also still quite uncommon in most other countries and may explain why the UK has such a bad record with MRSA." Dr Enright believes that proven measures that interrupt transmission of MRSA between patients, such as frequent hand-washing and patient isolation, are more likely to have an impact on infection rates than measures to improve general hospital cleanliness. There has been no real scientific evidence that 'cleaner' hospitals have lower rates of MRSA infection.
Link: HighWire Press -- Medline Abstract.
PFGE detected three major clones (in 93% of patients), all of which had been present in 1999-2000, although in different proportions. Whereas the predominant clone in 1999 was clone A (clone A 63%, clone B 20%), clone B was now found to predominate (clone B 58%, clone A 19%). None of these major clones were related to the five pandemic clones, including the Iberian clone, but two of them seemed to be related to the two most prevalent clones in Spain at this time. The new predominant clone was more resistant than the others, and showed uniform resistance to ciprofloxacin, erythromycin, clindamycin, and gentamicin. CONCLUSION. In recent years, a formerly predominant MRSA clone has been replaced by a multiresistant S. aureus clone that is unrelated to the Iberian clone.
Link: Journal of Clinical Microbiology.
Overall, a total of 16 genotypes based on sequence type and SCCmec types were identified among MRSA strains from Asian countries. Data revealed two major genotypes of MRSA strains in Asia, with unique geographic distributions. By MLST analysis, all strains from Korea and Japan except one belonged to clonal complex 5 (CC5) while most MRSA isolates from other Asian countries belonged to CC239. SCCmec typing showed that most isolates from Korea and Japan were SSmec type II whereas SCCmec type III (or IIIA) was the most common type in strains from other Asian countries. Our data documented a unique geographic distribution and evolutionary pattern of MRSA clones in Asia.
Link: Journal of Clinical Microbiology.
A total of 1,838 subjects from the community and 393 subjects from health care-related facilities in Taiwan were evaluated for the prevalence of nasal Staphylococcus aureus colonization and to identify risk factors associated with S. aureus and methicillin-resistant S. aureus (MRSA) colonization. In conclusion, a high prevalence of MRSA colonization was observed among people with no relationship to the hospital setting. The high level of multiple-drug resistance among community MRSA strains in association with the previously reported excessive use of antibiotics in Taiwan highlights the importance of the problem of antibiotic selective pressure. Our results indicate that both the clonal spread of MRSA and the transmission of hospital isolates contribute to the high MRSA burden in the community.
Link: Antimicrobial Agents and Chemotherapy.
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.
Link: News Medical Net.
Scientists have discovered that factors such as human immunity and drug resistance are less important to the success of bacterial spread than previously thought. According to research published online this week in Proceedings of the National Academy of Sciences most of the variation in the spread of bacterial pathogens occurs simply by chance.
The team from Imperial College London studied three famously deadly species: Neisseria meningitidis, which causes outbreaks of meningitis; Streptococcus pneumoniae, which kills 1.8 million people around the world every year, and Staphylococcus aureus, which in its drug resistant form is better known as MRSA.
They compared the genetic make-up of these bacteria with a computer simulation which allowed them to test various evolutionary scenarios.
Link: The Journal of Bacteriology.
Much of the research aimed at defining the pathogenesis of Staphylococcus aureus has been done with a limited number of strains, most notably the 8325-4 derivative RN6390. Several lines of evidence indicate that this strain is unique by comparison to clinical isolates of S. aureus. Based on this, we have focused our efforts on two clinical isolates (UAMS-1 and UAMS-601), both of which are hypervirulent in our animal models of musculoskeletal infection. In this study, we used comparative genomic hybridization to assess the genome content of these two isolates relative to RN6390 and each of seven sequenced S. aureus isolates.
Link: HighWire Press -- Medline Abstract.
Data revealed two major genotypes of MRSA strains in Asia, with unique geographic distributions. By MLST analysis, all strains from Korea and Japan except one belonged to clonal complex 5 (CC5) while most MRSA isolates from other Asian countries belonged to CC239. SCCmec typing showed that most isolates from Korea and Japan were SSmec type II whereas SCCmec type III (or IIIA) was the most common type in strains from other Asian countries. Our data documented a unique geographic distribution and evolutionary pattern of MRSA clones in Asia.
Link: Journal of Clinical Investigation.
S. aureus strains can express a wide array of potential virulence factors (Figure 1), including surface proteins that promote adherence to damaged tissue (9), bind proteins in blood to help evade antibody-mediated immune responses (9), and promote iron uptake (10). The organism also expresses a number of membrane-damaging toxins and superantigen toxins that can cause tissue damage and the symptoms of septic shock, respectively (11). There is a growing realization that S. aureus has multiple mechanisms for evading both innate immunity mediated by polymorphonuclear leukocytes (12, 13) and induced immunity mediated by both B and T cells (11, 14). Some virulence factors are expressed by genes that are located on mobile genetic elements called pathogenicity islands (e.g., toxic shock syndrome toxin–1 and some enterotoxins; ref. 15) or lysogenic bacteriophages (e.g., Panton-Valentine leucocidin [PVL]; refs. 15, 16) and factors associated with suppressing innate immunity such as the chemotaxis inhibitory protein and staphylokinase (ref. 13), which are integrated in the bacterial chromosome.
Link: Medical News Today.
Staphylococcus aureus causes a wide variety of diseases including boils and furuncles and more serious diseases such as septicemia and pneumonia, and a debate has long raged about the existence of S. aureus "superbugs" - more dangerous strains that may be associated with particularly invasive disease. In the December 15 issue of the Journal of Clinical Investigation, Damian Melles and colleagues from University Medical Center Rotterdam examined 829 S. aureus strains from healthy donors from the city of Rotterdam. The genetic relatedness of the strains was compared and revealed the existence of 3 major and 2 minor genetic clusters. These clusters corresponded to the predominant genetic groups identified in a similar analysis recently performed in the United Kingdom, indicating that the same clonal lineages of the organism appear to be dominant in 2 distinct geographic locations. Surprisingly, while the 2003 UK-based study found no evidence of hypervirulent clones or "superbugs" assocated with particularly invasive forms of disease, Melles et al. examined isolates from individuals with bacteriemia, deep-seated abscesses, or impetigo and found clear evidence that some strains of S. aureus are more virulent that others in that they appear more frequently in people with serious S. aureus-related disease that healthy individuals that simply carry the organism without falling prey to infection.
Link: Evening Telegraph
im Wallace visited the Scottish Structural Proteomics Facility (SSPF) at the University of St Andrews to see for himself the work being done to battle deadly infections. The centre, a collaboration with the University of Dundee, will conduct critical research with the aim of creating more effective medicines for dangerous diseases including MRSA. Mr Wallace said, “This is the most modern basic research facility in Britain for drug design work. Facilities like this enable cutting edge research and are critical to ensuring Scotland can both retain home grown talent and attract top scientists from overseas. There are 14 research groups contributing to the SSPF, including scientists from Glasgow and Warwick Universities. The project will be overseen by Professors James Naismith and Malcolm White of St Andrews and Bill Hunter from Dundee University. Professor Naismith said, “The study of the structure of proteins is essential in the fight against drug resistant bacteria, viruses and parasites, which afflict many people in Scotland and the world. “The UK has lagged behind in this field recently despite discovering and developing the technique in 1960s. Currently the USA, EU and Japan have major programmes in this area, which are nearly 100 times larger than the UK.” The lab will house large-scale robotic equipment with cloning and expression technology and the team also hopes to discover more about proteins and enzymes, which will allow them to design more effective medicines.
Link: HighWire Press -- Medline Abstract.
This type of information will guide drug strategy
The proportion of T5 MRSA increased significantly (years 1-2: 41%; years 3-4: 65%; years 5-6: 90%, P<0.001). This large sample of patients with serious S. aureus infection confirms that capsular polysaccharides T5 and T8 cause most human infections, and together with serotype 336, account for nearly all those with bacteraemia.
Link: NEWS.com.au
A MAJOR study has begun into potentially fatal hospital superbugs which infected almost 800 people across New South Wales last year. Researchers hope to locate the origins of antibiotic-resistant genes in a bid to stop the superbugs. Fears were raised after diseases such as cholera with antibiotic resistant genes were found in water in hospital vases. A Macquarie University research team is now conducting the study into how widespread the genes are among healthy people. The antibiotic-resistant genes have also led to the re-emergence of diseases such as tuberculosis and hospital superbug methicillin resistant staphylococcus aureus (MRSA), with experts yesterday predicting an increasing number of cases as they continue to mutate.
Link: Microbiology.
Variable-number tandem repeats (VNTRs) have been shown to be a powerful tool in the determination of evolutionary relationships and population genetics of bacteria. The sequencing of a number of Staphylococcus aureus genomes has allowed the identification of novel VNTR sequences in S. aureus, which are similar to those used in the study of the evolution of Mycobacterium tuberculosis clades. Seven VNTRs, termed staphylococcal interspersed repeat units (SIRUs), distributed around the genome are described, occurring in both unique and multiple sites, and varying in length from 48 to 159 bp. Variations in copy numbers were observed in all loci, within both the sequenced genomes and the UK epidemic methicillin-resistant S. aureus (EMRSA) isolates. Clonally related UK EMRSA isolates were clustered using SIRUs, which provided a greater degree of discrimination than multi-locus sequence typing, indicating that VNTRs may be a more appropriate evolutionary marker for studying transmission events and the geographical spread of S. aureus clades.
Link: HighWire Press -- Medline Abstract.
The study describes the detection of a gentamicin-susceptible heterogeneous MRSA clone that resembles another MRSA clone widely spread in US and Japanese hospitals, and supports the premise that the detection of heterogeneous MRSA isolates by some recommended methods is a challenging task that may, occasionally, result in MRSA misidentification.
Link: This is Oxford.
Doctors have discovered a new strain of the superbug MRSA among Oxfordshire patients, which they believe has evolved outside the county's hospitals. Experts said the latest type of the bacterium was treatable, but could hamper attempts to reduce infection on NHS wards if patients were already contaminated when they were admitted. MRSA - methicillin resistant Staphyloccus aureas -- is a strain of the bacteria S. aureas, which is resistant to normal types of antibiotic. Although all S. aureas is dangerous to vulnerable people when they become infected through an open wound, MRSA is more difficult to treat.
Link: MedicalPost.com.
In the last 10 years, MRSA rates have skyrocketed to the point that the infection now accounts for 65% of the Staph strains seen in children presenting to the University of Chicago Children's Hospital, where Dr. Daum is professor of pediatrics. "At other institutions in this country (the U.S.), like Texas Children's Hospital, the rate is now over 80%," Dr. Daum said. "The good news, as one of my colleagues joked, is it can only go as high as 100%. The bad news is it's increasing with amazing speed." The main reason for that increase is thought to be a "sleeked down" small DNA cassette that Staph aureus has developed that is capable of spreading resistance from strain to strain.
Virulent strains in community
"This small cassette appears to be parasitizing methicillin-sensitive Staph strains and converting them to methicillin-resistant strains. We believe this insertion has happened multiple times, and survivors of the insertion are the strains that are best able to infect us. We're seeing an evolutionary process that has made a class of more virulent MRSA strains circulating in the community." While most of the community-acquired MRSA causes skin and soft tissue infections that can be dealt with on an outpatient basis, some of them cause very much more severe disease, including necrotizing pneumonia, septic shock and death.