A Field Guide to Pandemic, Epidemic and Sporadic Clones of Methicillin-Resistant Staphylococcus aureus

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) have become a truly global challenge. In addition to the long-known healthcare-associated clones, novel strains have also emerged outside of the hospital settings, in the community as well as in livestock. The emergence and spread of virulent clones expressing Panton-Valentine leukocidin (PVL) is an additional cause for concern. In order to provide an overview of pandemic, epidemic and sporadic strains, more than 3,000 clinical and veterinary isolates of MRSA mainly from Germany, the United Kingdom, Ireland, France, Malta, Abu Dhabi, Hong Kong, Australia, Trinidad & Tobago as well as some reference strains from the United States have been genotyped by DNA microarray analysis. This technique allowed the assignment of the MRSA isolates to 34 distinct lineages which can be clearly defined based on non-mobile genes. The results were in accordance with data from multilocus sequence typing. More than 100 different strains were distinguished based on affiliation to these lineages, SCCmec type and the presence or absence of PVL. These strains are described here mainly with regard to clinically relevant antimicrobial resistance- and virulence-associated markers, but also in relation to epidemiology and geographic distribution. The findings of the study show a high level of biodiversity among MRSA, especially among strains harbouring SCCmec IV and V elements. The data also indicate a high rate of genetic recombination in MRSA involving SCC elements, bacteriophages or other mobile genetic elements and large-scale chromosomal replacements

A Field Guide to Pandemic, Epidemic and Sporadic Clones of Methicillin-Resistant Staphylococcus aureus

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) have become a truly global challenge. In addition to the long-known healthcare-associated clones, novel strains have also emerged outside of the hospital settings, in the community as well as in livestock. The emergence and spread of virulent clones expressing Panton-Valentine leukocidin (PVL) is an additional cause for concern. In order to provide an overview of pandemic, epidemic and sporadic strains, more than 3,000 clinical and veterinary isolates of MRSA mainly from Germany, the United Kingdom, Ireland, France, Malta, Abu Dhabi, Hong Kong, Australia, Trinidad & Tobago as well as some reference strains from the United States have been genotyped by DNA microarray analysis. This technique allowed the assignment of the MRSA isolates to 34 distinct lineages which can be clearly defined based on non-mobile genes. The results were in accordance with data from multilocus sequence typing. More than 100 different strains were distinguished based on affiliation to these lineages, SCCmec type and the presence or absence of PVL. These strains are described here mainly with regard to clinically relevant antimicrobial resistance- and virulence-associated markers, but also in relation to epidemiology and geographic distribution. The findings of the study show a high level of biodiversity among MRSA, especially among strains harbouring SCCmec IV and V elements. The data also indicate a high rate of genetic recombination in MRSA involving SCC elements, bacteriophages or other mobile genetic elements and large-scale chromosomal replacements

Incorporation of Peptides Targeting EGFR and FGFR1 into the Adenoviral Fiber Knob Domain and Their Evaluation as Targeted Cancer Therapies

Oncolytic virotherapies based on Adenovirus 5 (Ad5) hold promise as adjunctive cancer therapies; however their efficacy when delivered systemically is hampered by poor target cell specificity and pre-existing anti-Ad5 immunity. Ovarian cancer represents a promising target for virotherapy, since the virus can be delivered locally into the peritoneal cavity. Both Epidermal Growth Factor Receptor (EGFR) and Fibroblast Growth Factor Receptor 1 (FGFR1) are over-expressed in the majority of human tumours, including ovarian cancer. To generate adenoviral vectors with improved tumour specificity, we generated a panel of Ad5 vectors with altered tropism for EGFR and FGFR, rather than the natural Ad5 receptor, hCAR. We have included mutations within AB loop the viral fibre knob (KO1 mutation) to preclude interaction with, hCAR, combined with insertions in the HI loop to incorporate peptides that bind either EGFR (peptide YHWYGYTPQNVI, GE11) or FGFR1 (peptides MQLPLAT, M* and LSPPRYP, LS). Viruses were produced to high titres, and the integrity of the fibre protein was validated by Western blotting. The KO1 mutation efficiently ablated hCAR interactions, and significantly increased transduction was observed in hCARlow/EGFRhigh cell lines using Ad5.GE11, whilst transduction levels using Ad5.M* or Ad5.LS were not increased. In the presence of physiological concentrations of human blood clotting factor X (hFX), significantly increased levels of transduction via the hFX-mediated pathway were observed in cell lines, but not in primary tumour cells derived from epithelial ovarian cancer (EOC) ascites samples. Ad5 mediated transduction of EOC cells were completely abolished by the presence of 2.5% serum from patients, whilst surprisingly, incorporation of the GE11 peptide resulted in significant evasion of neutralisation in the same samples. We thus speculate that incorporation of the YHWYGYTPQNVI dodecapeptide within the fibre knob domain may provide a novel means of circumventing pre-existing Ad5 immunity that warrants further investigation

Dynamic spectrum access for machine to machine communications: Opportunities, standards, and open issues

Cognitive radio can be applied to a multitude of domains, one of which is M2M communication. Specifically, M2M communication refers to communication between devices without human intervention. Hence, devices should be able to organize themselves and run the communication protocol autonomously. If cognitive radio is used, tasks such as dynamic spectrum access (DSA), spectrum sensing, and alike present additional challenges compared to traditional network, as all the decision framework should be implemented and automatized in the devices. In this chapter, we focus on DSA techniques for M2M. The main difference from other kinds of communication is relative both to the energy efficiency and to the low protocol overhead, as devices should run for long periods of time and run without human intervention. At first we present related work from literature, categorizing the different tasks devices which want to leverage DSA on M2M have to perform. At the end of the chapter, we present a proof of concept of a general framework, which can be applied to different scenario concerning M2M, encompassing all the spectrum management and measurement tasks M2M devices should generally perform. Finally, we derive open challenges and future research directions concerning this scenario