MRSA Infection

Staphylococcus aureus Protein A Polymorphic Region Regulates Inflammation: Impact on Acute and Chronic Infection

The Length of the Staphylococcus aureus Protein A Polymorphic Region Regulates Inflammation: Impact on Acute and Chronic Infection.

Staphylococcus aureus protein A (SpA) plays a critical role in the induction of inflammation. This study was aimed to determine whether the number of short sequence repeats (SSRs) present in the polymorphic region modulates the inflammatory response induced by SpA. We demonstrated that there is a dose-response effect in the activation of interferon (IFN)-β signaling in airway epithelial and immune cells, depending on the number of SSRs, which leads to differences in neutrophil recruitment. We also determined that a significant proportion of isolates from patients with chronic infections such as osteomyelitis and cystic fibrosis carry fewer SSRs than do isolates from patients with acute infections or healthy carriers and that there was an inverse correlation between the number of SSRs and the length of disease course. Given the importance of IFN signaling in eradication of S. aureus, loss of SSRs may represent an advantageous mechanism to adapt to and persist in the host.

Survival of Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE) for an extended period of transport

Survival of Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE) for an extended period of transport.

This study determined the survivability of Methicillin- resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococci (VRE) for extended periods of time and temperatures using a standard swab for assessment. Our study showed that transportation in Liquid Amies could be performed at room temperature or 4°C for up to 14 days without a decrease in recovery of MRSA or VRE.

NIH scientists link quickly spreading gene to Asian MRSA epidemic | Science Codex

NIH scientists link quickly spreading gene to Asian MRSA epidemic | Science Codex.

National Institutes of Health (NIH) scientists and their colleagues in China have described a rapidly emerging Staphylococcus aureus gene, called sasX, which plays a pivotal role in establishing methicillin-resistant S. aureus (MRSA) epidemics in most of Asia. Senior author Michael Otto, Ph.D., of NIH's National Institute of Allergy and Infectious Diseases, says these findings illustrate at the molecular level how MRSA epidemics may emerge and spread. Previous data indicated that the sasX gene is extremely rare. Therefore, the researchers were surprised when they analyzed 807 patient samples of invasive S. aureus taken over the past decade from three Chinese hospitals. Their data showed that sasX is more prevalent in MRSA strains from China than previously thought, and the gene's frequency is increasing significantly: From 2003 to 2011, the percentage of MRSA samples containing sasX almost doubled, from 21 to 39 percent.

Scientists employ metagenomics to identify new possible antibiotics against MRSA

Scientists employ metagenomics to identify new possible antibiotics against MRSA.

The researchers removed DNA from soil bacteria that wouldn't grow in the lab. Then, they put this DNA into different bacteria that do grow well in culture dishes, and these bacteria acted like incubators for the new DNA. The approach enabled Brady's team to study the substances made by the soil bacteria's DNA in the lab. With this "metagenomics" method, they identified two new possible antibiotics called fasamycin A and fasamycin B that killed MRSA and vancomycin-resistant Enterococcus faecalis, which also is becoming more resistant to known antibiotics. They also determined how the new antibiotics work. "Metagenomics has the potential to access large numbers of previously inaccessible natural antibiotics," say the researchers.

Complete Genome Sequence of Staphylococcus aureus M013, a pvl-Positive, ST59-SCCmec Type V Strain Isolated in Taiwan

Complete Genome Sequence of Staphylococcus aureus M013, a pvl-Positive, ST59-SCCmec Type V Strain Isolated in Taiwan.

We report the complete genome sequence of M013, a representative strain of a pvl-positive, sequence type 59-staphylococcal cassette chromosome mec type V (ST59-SCCmec type V) community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone in Taiwan. Comparison of M013 with the genomes of two CA-MRSA strains in the United States revealed major differences in the regions covering several genomic islands and prophages.

Persistent MRSA - Why some people are more vulnerable

Progress Made in Developing Community-Acquired MRSA Vaccine: Scientific American.

Daum's hunch was right: the girl had a mutation that Holland had recently linked to a rare immunodeficiency called Job's syndrome. People with the syndrome have persistent, smouldering S. aureus infections, owing to an inability to make a type of lymphocyte, or immune cell, called a TH17 cell. These cells, which make a proinflammatory protein called interleukin-17, have become a hot topic in vaccine research. They are produced by a different branch of the immune system from the one that makes antibodies, yet they still seem to be involved in the body's memory of exposures to pathogens. Daum believes that TH17 cells are the key to an S. aureus vaccine. "It looks like T cells are very important in staphylococcal immunity," he says.

Genetic change: a Case Study of Staphylococcus aureus

Population Genomics in Bacteria: A Case Study of Staphylococcus aureus.

We analyzed the genome-wide pattern of single nucleotide polymorphisms (SNPs) in a sample with 12 strains of Staphylococcus aureus. Population structure of S. aureus seems to be complex, and the 12 strains were divided into five groups, named A, B, C, D, and E. We conducted a detailed analysis of the topologies of gene genealogies across the genomes and observed a high rate and frequency of tree-shape switching, indicating extensive homologous recombination. Our results call for more research into the evolutionary role of homologous recombination in bacterial populations.

How Staphylococcus aureus biofilms develop their characteristic structure

How Staphylococcus aureus biofilms develop their characteristic structure.

Our study describes a mechanism of biofilm structuring in molecular detail, and the general principle (i.e., quorum-sensing controlled expression of surfactants) seems to be conserved in several bacteria, despite the divergence of the respective biofilm-structuring surfactants. These findings provide a deeper understanding of biofilm development processes, which represents an important basis for strategies to interfere with biofilm formation in the environment and human disease.

Making medicine from MRSA

Nature lessons | Mending Broken Hearts | guardian.co.uk.

At the Institute of Cardiovascular and Metabolic Research at the University of Reading, Dr Simon Clarke has discovered a potential therapeutic use of a molecule produced by the MRSA super bug. "We've discovered that the bacteria staphylococcus aureus produces something called lipoteichoic acid and we've found that it can inhibit activation of platelets," explains Clarke. Platelets have an important role in blood clotting, and although clotting is an important response to injury, it can also be dangerous in some circumstances, including during a heart attack, when a blood clot in an artery starves the heart of vital oxygen. "We're studying how platelets respond to the lipoteichoic acid in order to understand how we can prevent them from activating," says Clarke. "Inappropriate activation of platelets leads to thrombosis, causing heart attacks and strokes."

Digging deep in the MRSA family tree

Molecular differentiation of historic phage-type 80/81 and contemporary epidemic Staphylococcus aureus.

To better understand the molecular basis of these epidemics, we sequenced the genomes of eight S. aureus clinical isolates representative of the phage-type 80/81 clone, the Southwest Pacific clone [a community-associated methicillin-resistant S. aureus (MRSA) clone], and contemporary S. aureus clones, all of which are genetically related and belong to the same clonal complex (CC30). Genome sequence analysis revealed that there was coincident divergence of these clones from a recent common ancestor, a finding that resolves controversy about the evolutionary history of the lineage. Notably, we identified nonsynonymous SNPs in genes encoding accessory gene regulator C (agrC) and α-hemolysin (hla)—molecules important for S. aureus virulence—that were present in virtually all contemporary CC30 hospital isolates tested. Compared with the phage-type 80/81 and Southwest Pacific clones, contemporary CC30 hospital isolates had reduced virulence in mouse infection models, the result of SNPs in agrC and hla. We conclude that agr and hla (along with penicillin resistance) were essential for world dominance of phage-type 80/81 S. aureus, whereas key SNPs in contemporary CC30 clones restrict these pathogens to hospital settings in which the host is typically compromised.

Bullfrog toxin helps map MRSA weakness

BBC News - Gene clue to how superbugs attack.

The experts studied a toxin from the skin of a bullfrog that kills MRSA. They used lab tests and computer analysis to show the agent does this by weakening both the wall of the bacterium and its membrane. They also put together a map of the relationships between most of the bacterium's genes. The findings may help in the development of new therapies. Professor Nick Hastie of the MRC Human Genetics Unit in Edinburgh said: "This work is a fine example of the relationship between analysing the fundamental processes which help infections to take hold and exploiting this knowledge to improve drug treatments."

New form of MRSA found in Dublin hospitals

New form of MRSA found in Dublin hospitals and British milk | BreakingNews.ie.

Scientists have found a completely new form of the MRSA superbug in two Dublin hospitals. The Irish research team believes the new organism probably made the jump from animals into humans. Professor David Coleman from Trinity College Dublin, who led the research, said this strain had never been seen before in any living organism.

New MRSA related to Strain 130 - only seen in cows before

Study provides insights into evolution and origins of MRSA.

The MRSA strain was found to belong to the genetic lineage clonal complex 130 (CC130), which has previously only been associated with MSSA from cows and other animals, but not humans, strongly suggesting that the new MRSA originated in animals.

Finding the key genetic roots of MRSA drug resistance

Structural and functional analyses reveal that Staphylococcus aureus antibiotic resistance factor HMRA is a zinc-dependent endopeptidase..

HmrA is an antibiotic resistance factor of methicillin-resistant Staphylococcus aureus (MRSA). Molecular analysis of this protein revealed it is not a muramidase or β-lactamase but an unspecific double-zinc endopeptidase consisting of a catalytic domain and an inserted oligomerization domain, which likely undergo a relative interdomain hinge rotation upon substrate binding. The active-site cleft is located at the domain interface. Four HmrA protomers assemble to a large ~170-kDa homotetrameric complex of 125Å. All four active sites are fully accessible and ~50-70Å apart, far enough apart to act on a large meshwork substrate independently but simultaneosuly. In vivo studies with four S. aureus strains of variable resistance levels revealed that extracellular addition of HmrA protects against loss of viability in the presence of oxacillin and that this protection depends on proteolytic activity. All these results indicate that HmrA is a peptidase that participates in resistance mechanisms in vivo in the presence of β-lactams. Furthermore, our results have implication for most S. aureus strains of known genomic sequences and several other cocci and bacilli, which harbor close orthologs. This suggests that HmrA may be a new widespread antibiotic resistance factor in bacteria.

Space mission targets MRSA cures in microgravity

Targets against MRSA in microgravity.

NASA astronauts onboard Space Shuttle Discovery's final mission to the International Space Station (ISS) will carry out the eleventh scientific payload for Astrogenetix, a commercial biotech company based out of Austin, Texas. The research on STS-133 will focus on changes that occur to methicillin-resistant Staphylococcus aureus (MRSA) in microgravity, which can be targeted to create new vaccines and therapeutics.

Targeting MRSA Biofilm: Genetic insights

Essential Role for the Major Autolysin in the Fibronectin-Binding Protein-Mediated Staphylococcus aureus Biofilm Phenotype -- Houston et al. 79 (3): 1153 -- Infection and Immunity.

Consistent with these observations, extracellular DNA was important for the early stages of Atl/FnBP-dependent biofilm development. Further analysis of atl regulation revealed that atlR encodes a transcriptional repressor of the major autolysin and that an atlR::Tcr mutation in BH1CC enhanced biofilm-forming capacity. These data reveal an essential role for the major autolysin in the early events of the FnBP-dependent S. aureus biofilm phenotype.

MRSA uses body defences as fuel

Host Chemokines Bind to Staphylococcus aureus and Stimulate Protein A Release — JBC.

There are few examples of host signals that are beneficial to bacteria during infection. Here we found that 31 out of 42 host immunoregulatory chemokines were able to induce release of the virulence factor protein A (SPA) from a strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Detailed study of chemokine CXCL9 revealed that SPA release occurred through a post-translational mechanism and was inversely proportional to bacterial density. CXCL9 bound specifically to the cell membrane of CA-MRSA, and the related SPA-releasing chemokine CXCL10 bound to both cell wall and cell membrane. Clinical samples from patients infected with S. aureus and samples from a mouse model of CA-MRSA skin abscess all contained extracellular SPA. Further, SPA-releasing chemokines were present in mouse skin lesions infected with CA-MRSA. Our data identify a potential new mode of immune evasion, in which the pathogen exploits a host defense factor to release a virulence factor; moreover, chemokine binding may serve a scavenging function in immune evasion by S. aureus.

Virulence Genes in MRSA

Distribution of Virulence Genes in spa Types of Me... [Korean J Lab Med. 2011] - PubMed result.

BACKGROUND: Various virulence factors and superantigens are encoded by mobile genetic elements. The relationship between clonal background and virulence factors differs in different geographic regions. We compared the distribution and relationship of spa types and virulence genes among methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from a tertiary hospital in 2000-01 and 2007-08. METHODS: In 2000-01 and 2007-08, 94 MRSA strains were collected from 3 intensive care units at a Korean tertiary hospital. We performed spa typing and multiplex PCR for 19 superantigen genes. RESULTS: Relatively frequent spa types were t037 (40.5%), t002, t601, and t2138 in 2000-01, and t2460 (43.9%), t002, t037, t601, t324, and t2139 in 2007-08. We identified 4 novel spa types, 2 of which were designated as t5076 and t5079. Superantigen profiles were closely linked to spa types. For example, sea, sek, and seq superantigen genes were mainly detected in t037 strains. CONCLUSIONS: Major spa types differed depending on study periods, and the distribution of superantigen genes correlated with spa type.

MRSA Evolves Every 15 weeks

Pneumonia Drugs Helped Evolve A Superbug - Science News.

The PMEN1 strain contributes to these totals and, because of its resistance to several different antibiotics, has become a public health concern. The strain is considered a major cause of pneumonia, meningitis and other infections worldwide. The new study reveals some of the genetic tricks the organism used to develop drug resistance. Since its emergence, the strain has changed one of its DNA letters about every 15 weeks, the analysis reveals. That rate of mutation is rapid but similar to rates seen in the deadly antibiotic-resistant Staphylococcus aureus bacteria commonly called MRSA. The strain also occasionally swaps or recombines DNA with other bacteria, and such recombination may be far more important in developing drug resistance. Each DNA-swapping episode brings about 72 single-letter changes on average and sometimes introduces entirely new genes, or new versions of genes.

20% of MRSA infections have aggressive mutation

Increased Mortality with Accessory Gene Regulator (agr)-Dysfunction in Staphylococcus aureus among Bacteremic Patients -- Schweizer et al., 10.1128/AAC.00918-10 -- Antimicrobial Agents and Chemotherapy.

Among 814 patient-admissions complicated by S. aureus bacteremia, 181 (22%) were infected with S. aureus isolates with agr-dysfunction. Overall, 18% of patients with agr-dysfunction in S. aureus died compared to 12% with functional agr (p=0.03). There was a trend toward higher mortality among patients with agr-dysfunctional S. aureus (adjusted hazard ratio (HR): 1.34; 95% confidence interval (CI): 0.87, 2.06). Among patients with the highest APS (score>28), agr-dysfunction in S. aureus was significantly associated with mortality (adjusted HR=1.82; 95% CI: 1.03, 3.21). This is the first study to demonstrate an independent association between agr-dysfunction and mortality among severely ill patients. The delta-hemolysin assay examining agr function may be a simple and inexpensive approach to predicting patient outcomes and potentially to optimize antibiotic therapy.