MRSA (Mersa, Staph) Questions

MRSA goes dormant and the reinfects

Link: .

A major cause of human and animal infections, Staphylococcus aureus bacteria may evade the immune system’s defences and dodge antibiotics by climbing into our cells and then lying low to avoid detection. New research shows how S. aureus makes itself at home in human lung cells for up to two weeks. They found that shortly after S. aureus entered the lung cells, the bacteria’s gene expression profile dramatically changed: gene expression for bacterial metabolic functions and transport shut down, putting the bacteria in a dormant state. Simultaneously, production of toxins potentially lethal for the epithelial cells becomes strictly controlled to limit cellular damage. Mechanisms that helped the bacteria to survive and/or multiply, including metabolic and energy production functions, then resumed. Although most of the bacteria had died by about four days as a result of antibiotic treatment, the team still found viable bacteria in their model system two weeks after infection. The findings may help in understanding persistent infections, and in designing new antibacterial drugs. S. aureus has not traditionally been considered an intracellular pathogen, but the molecular details that govern its extended persistence remain largely unknown. The bacteria can generate relapsing infections even years after the first episode was apparently cured.

Different MRSA strains more invasive

Link: HighWire Press -- Medline Abstract.

Patients in intensive care units are at high risk of developing methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We report an epidemiological and bacterial genomic analysis of a 2-year outbreak in an intensive care unit of a variant of MRSA sequence type 239 (hereafter designated TW). METHODS: A cohort study was conducted to compare risk factors for MRSA bacteremia in patients who acquired TW versus patients who acquired non-TW strains of MRSA. Genetic analysis of TW was performed using multilocus sequence typing and microarray analysis. RESULTS: Patients who acquired TW were more likely than patients who acquired non-TW strains of MRSA to have MRSA isolated from blood samples (47% vs. 13%; P<.001) and to have MRSA-positive vascular access device-sample cultures (59% vs. 26%; P<.001), but less likely to have MRSA isolated from screening swab samples (30% vs. 71%; P<.001). This increased rate of TW bacteremia was confined to the first week after acquisition of TW infection. Using Cox regression analysis, the adjusted hazard ratio for bacteremia with TW was 4.5 times that of non-TW strains of MRSA (95% confidence interval, 2.25-9.00; P<.001). Microarray analysis revealed that TW had accumulated all detectable mobile genetic elements that were variably expressed by other epidemic strains of MRSA sequence type 239 in the United Kingdom. CONCLUSIONS: To our knowledge, this is the first report to provide direct evidence that strains of MRSA can differ in their ability to cause bacteremia. Further genetic and in vitro analysis of the TW strain may provide insight into the mechanism of vascular access device-related bacteremia in the intensive care unit environment.

Genetic differences between HA MRSa and CA MRSA

Link: HighWire Press -- Medline Abstract.

Measurements and Main Results. All tested MRSA isolates were susceptible to daptomycin, linezolid, and vancomycin. In addition, community-associated MRSA isolates were significantly (all p 48 hrs after admission and according to the CDC definition) possessed SCCmec type IV. Conclusion. Overall, inducible clindamycin resistance occurred at significantly higher rates in the hospital-associated MRSA isolates, susceptibility differed significantly between community- and hospital-associated MRSA, and most of the hospital isolates contained SCCmec type IV.

MRSA and Cystic Fibrosis - assessing the impact

Link: Journal of Clinical Microbiology.

Small colony variants (SCVs) of Staphylococcus aureus can be isolated from the chronically infected airways of patients suffering from cystic fibrosis (CF). These slow-growing morphological variants have been associated with persistent and antibiotic-resistant infections, such as osteomyelitis and device-related infections, but no information is available to date regarding the clinical significance of this special phenotype in CF lung disease. We therefore investigated the prevalence of S. aureus SCVs in CF lung disease in a 12-month prospective study and correlated the microbiological culture results with the patients' clinical data. A total of 252 patients were screened for the presence of SCVs. The prevalence rate was determined to be 17% (95% confidence interval, 10%-25%) among S. aureus carriers. S. aureus isolates with SCV phenotype showed significantly higher antibiotic resistance rates than those with normal phenotype. Patients positive for SCVs were significantly older (P = 0.0099), more commonly co-colonized with P. aeruginosa (P = 0.0454), and showed signs of more advanced disease, such as lower FEV1 values (P = 0.0148) than patients harboring S. aureus with solely normal phenotype. The logistic regression model determined lower weight (P = 0.016), advanced age (P = 0.000), and prior use of trimethoprim-sulfamethoxazole (P = 0.002) as independent risk factors for S. aureus SCV positivity. The clinical status of CF patients is known to be affected by multiple parameters. Nonetheless, the independent risk factors determined here point to the impact of S. aureus SCVs on chronic and persistent infections in advanced CF lung disease.

Some patients genetically prone to extreme MRSA reactions?

Link: Scientists Identify A Septic Shock Susceptibility Gene.

       In the November 15th issue of G&D, Dr. Robert Schneider and colleagues at NYU School of Medicine report that the AUF1 gene underlies susceptibility to septic shock. Septic shock often follows a bacterial infection, and is characterized by the overwhelming release of pro-inflammatory cytokines by the body's immune system. This uncontrolled, systemic inflammatory response leads to dangerously low blood pressure and, ultimately, organ failure. One quarter to one half of sepsis patients die, making it the leading cause of hospital deaths in the US.

PVL Strains of MRSA common in Japan

Link: Journal of Clinical Microbiology.

We examined 97 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated between 1979-1985, the period of time when the appearance of MRSA strains increased, and determined that these strains are distinct from the MRSA clones predominating in today's Japanese hospitals. Type-IV SCCmec strains were the most frequent, comprising 53.6% of all strains, followed by type-I (22.7%) and type-II (21.6%) SCCmec strains. Among the type-IV SCCmec strains, the frequencies of two new subtypes, type-IV.3 (IVc) and type-IV.4 (IVd), were very high, comprising 38.1% and 10.3% of type-IV SCCmec strains, respectively. Forty-four of the 97 strains (45.3%) were Panton-Valentine Leucocidin (PVL)-positive. Among the PVL-positive strains, ST30-type-IV SCCmec strains producing type-4 coagulase were the most frequent. This is in striking contrast to the MRSA strains isolated in the 1990s, most of which were ST5-type-II SCCmec strains producing type-2 coagulase, and were positive for toxic shock syndrome toxin-1 (TSST1) gene. We also identified a new PVL-carrying prophage lysogenized in a type-IV.3 SCCmec strain 81/108. {varphi}108PVL was distinct from the three extant PVL-carrying phages, and was presumed to be carried by ST30-type-IV.3 SCCmec strains isolated in Japan. These results provide genetic bases for the transition of MRSA clones in Japan commonly considered as the transition from coagulase type-4 MRSA strains to coagulase type-2 MRSA strains. The results also suggested that MRSA strains that predominated in the years 1979-1985 were generated from PVL-positive MSSA strains through the integration of SCCmec elements.

Japanese suggest rapid method of identifying MRSA strains

Link: HighWire Press -- Medline Abstract.

      MRSA isolates collected in Japan can be genotyped by detecting the keeping pattern of phage-derived ORFs with a discriminatory power equal to that of PFGE subtyping. Significance and Impact of the Study: MRSA isolates can be genotyped rapidly by detecting phage-derived ORFs. As particular pandemic clones can be found in a specific region, a typing method localized to a pandemic clone may be effective for the rapid genotyping of MRSA during outbreaks.

MRSA still evolving

Link: HighWire Press -- Medline Abstract.

    In total, 150 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected during 2002 from a general Belgian hospital were phage-typed at routine test dilution x 100. The majority (45%) belonged to phage group (J)*, while 10% were classified as a new phage type 29/(42E)/54/(D11)*. The isolates belonging to this new type carried the aac(6')-aph(2'') and the aph(3') aminoglycoside resistance genes and showed high-level resistance to oxacillin. Molecular typing revealed that they belonged to the multiresistant clonal pulsed-field gel electrophoresis (PFGE) type D8. PFGE group D, characterised as genotype ST228-MRSA-I, has been present in Belgian hospitals since 1999.

Strain 16 taking over in Europe

Link: HighWire Press -- Medline Abstract.

     This study investigated the molecular epidemiology of meticillin-resistant Staphylococcus aureus (MRSA) in the University Hospital of the Canary Islands (HUC) in order to evaluate epidemiological changes over a six-year period. Clinical and epidemiological data were collected between May 2000 and December 2003, and isolates were subjected to pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), SCCmec typing and spa typing. Since 2000, the rate of MRSA infections has increased at the HUC, coinciding with the emergence and spread of the EMRSA-16 clone (ST36-MRSA-II) and replacement of the Iberian clone (ST247-MRSA-I). Genotypic changes were associated with changes in the epidemiological profile. The mean age and proportion of patients over 60 years old (P=0.01) and the proportion of respiratory infections (P=0.001) increased significantly. Gentamicin and tetracycline susceptibility of MRSA isolates increased (P<0.001) following the emergence of EMRSA-16. Combining PFGE, SCCmec and MLST has been instrumental in understanding these changes and defining the clones circulating in the HUC patient population.

Discovering How MRSA Causes Infection

Link: Microbiology and Molecular Biology Reviews.

    The gram-positive bacterium Staphylococcus aureus is a frequent component of the human microbial flora that can turn into a dangerous pathogen. As such, this organism is capable of infecting almost every tissue and organ system in the human body. It does so by actively exporting a variety of virulence factors to the cell surface and extracellular milieu. Upon reaching their respective destinations, these virulence factors have pivotal roles in the colonization and subversion of the human host. It is therefore of major importance to obtain a clear understanding of the protein transport pathways that are active in S. aureus. The present review aims to provide a state-of-the-art roadmap of staphylococcal secretomes, which include both protein transport pathways and the extracytoplasmic proteins of these organisms. Specifically, an overview is presented of the exported virulence factors, pathways for protein transport, signals for cellular protein retention or secretion, and the exoproteomes of different S. aureus isolates. The focus is on S. aureus, but comparisons with Staphylococcus epidermidis and other gram-positive bacteria, such as Bacillus subtilis, are included where appropriate. Importantly, the results of genomic and proteomic studies on S. aureus secretomes are integrated through a comparative "secretomics" approach, resulting in the first definition of the core and variant secretomes of this bacterium. While the core secretome seems to be largely employed for general housekeeping functions which are necessary to thrive in particular niches provided by the human host, the variant secretome seems to contain the "gadgets" that S. aureus needs to conquer these well-protected niches.