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Genetic Research

Antibiotics in community change MRSA strains

Link: Recurrence of heterogeneous methicillin-resistant Staphylococcus aureus (MRSA) among the MRSA clinical isolates in a Japanese university hospital -- Kishii et al., 10.1093/jac/dkn186 -- Journal of Antimicrobial Chemotherapy.

Objectives: In the early 1980s, heterogeneous methicillin-resistant Staphylococcus aureus (hetero-MRSA) strains were predominant in the University of Tokyo Hospital. But, in the 1990s, they were completely substituted by homogeneously highly methicillin-resistant S. aureus (homo-MRSA) strains. Since 2000, however, we started observing an increase in MRSA strains with low cefazolin MICs (MRCLSA). This study was performed to understand the phenomenon by characterization of the ‘cefazolin-susceptible’ MRSA strains. Methods: A total of 39 MRCLSA strains were collected between July 2000 and June 2002 and compared with 10 homo-MRSA strains isolated during the same period for their antibiograms and genotypes. The strains were also compared with the hetero-MRSA strains isolated in the same hospital in the early 1980s. Results: In contrast to the homogeneous genotype [multilocus sequence type 5 and SCCmec type II.1 (IIa)] and multiresistant nature of the homo-MRSA strains, the MRCLSA strains were composed of various genotypes as revealed by multilocus sequence typing and SCCmec typing and had resistance only to a limited number of antibiotics. Most of the MRCLSA strains were also genetically differentiated from the hetero-MRSA strains of the 1980s. However, population analysis revealed that all of the MRCLSA strains were classified as hetero-MRSA strains. Conclusions: A new group of hetero-MRSA strains genetically distinct from those dominant in the same hospital in the early 1980s might have emerged in the community and started invading the university hospital. This phenomenon may be caused by the change in the pattern of antibiotic use.

Multiple MRSA Strains in Any Given Population

Link: HighWire Press -- Medline Abstract.

This study describes the distribution and frequencies of strain types by protein A-encoding gene (spa) typing among a total of 200 meticillin-resistant Staphylococcus aureus (MRSA) single-patient isolates collected between 2000 and 2005 at the University Hospital Basel, Switzerland. Nine frequent spa types accounted for 49.5 % of MRSA isolates, whereas spa type t041 (15 % of all isolates) belonged to a local epidemic strain that is also a common strain type in southern Germany. Successful control of the outbreak strain was documented by epidemiological data and confirmed by spa typing results. The spa type t044 (3.5 %), corresponding to a widely disseminated European community-acquired MRSA (CA-MRSA), was first observed in 2002. The well-known CA-MRSA USA300 clone was detected in four patients (2 %). Sporadic strains occurring less than four times (32 different spa types) accounted for 23 % of isolates. No predominant spa type was seen, indicating a great genetic diversity. Only 34.5 % of patient isolates were acquired nosocomially. The presence of one or more of ten common virulence genes was shown in 79 % of strains. It was demonstrated that the sequence-based spa typing method allows analysis of local MRSA epidemiology in relation to other regions and countries over time.

Notre Dame Researchers Say MRSA Drug Looks Promising

Link: KSDK NewsChannel 5 - Notre Dame Researchers Say MRSA Drug Looks Promising.

Dr. Mobashery's research focuses on a unique protein called Penicillin-binding protein 2a or PBP2a. A combination of organic chemistry, biochemistry and computational components led researchers to their discovery. Using goggles allowed us to get a 3-D look at the protein which is the target. "What we have here is the protein which is the target in MRSA," said Dr. Mobashery. "MRSA of course the difficult bacterium. This is a protein that actually exists in MRSA, the staph infection that is highly resistant to antibiotics." The green you see in the picture is the MRSA protein, and those sticks represent the drug researchers developed. "This is the protein that is indispensable to MRSA for its survival and by having this drug fitting into that cavity, what we have is a process that interferes with the daily existence of MRSA. MRSA cannot cope with it, and it dies," said Dr. Mobashery.

What makes staph resistant

Link: HighWire Press -- Medline Abstract.

Staphylococcus aureus is a Gram-positive human pathogen causing a wide variety of infections ranging from benign skin infections to life-threatening diseases. Furthermore, the spreading of multiresistance strains requiring the use of last-barrier drugs has resulted in the medical and scientific community focusing particularly on this pathogen. We describe here proteomic methods to prepare, identify, and analyze protein fractions, allowing the study of S. aureus on the organism level. Coupled with methods analyzing the whole bacterial transcriptome, this approach might contribute to the development of rapid diagnostic tests and to the identification of new drug targets.

MRSA - many sub strains

Link: HighWire Press -- Medline Abstract.

Staphylococcus aureus is a versatile pathogen associated with diverse clinical presentations. Only recently have the genetic factors underlying the virulence of this bacterial species become understood in a significant way. Methicillin-resistant S. aureus (MRSA) strains have been extremely important as nosocomial pathogens in health care facilities for more than three decades. Additionally, infections resulting from community-associated MRSA strains have emerged in the last decade and become a public health problem of global proportions. This changing epidemiology has spurred renewed interest in translating knowledge of the molecular determinants of virulence into rational prevention and control strategies. Four case histories are provided (three involving MRSA and one involving a methicillin-sensitive strain of S. aureus) that highlight the diversity of clinical presentations and relative virulence of S. aureus infections in humans. The molecular characterization of clonality and virulence gene profile is compared among the four cases. Significant genetic diversity exists among MRSA and sensitive strains of S. aureus. It is obvious that various combinations of virulence factors contribute to disease manifestations of infected patients.

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.

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