Engineered endolysin-based "artilysins" to combat multidrug-resistant gram-negative pathogens

The global threat to public health posed by emerging multidrug-resistant bacteria in the past few years necessitates the development of novel approaches to combat bacterial infections. Endolysins encoded by bacterial viruses (or phages) represent one promising avenue of investigation. These enzyme-based antibacterials efficiently kill Gram-positive bacteria upon contact by specific cell wall hydrolysis. However, a major hurdle in their exploitation as antibacterials against Gram-negative pathogens is the impermeable lipopolysaccharide layer surrounding their cell wall. Therefore, we developed and optimized an approach to engineer these enzymes as outer membrane-penetrating endolysins (Artilysins), rendering them highly bactericidal against Gram-negative pathogens, including Pseudomonas aeruginosa and Acinetobacter baumannii. Artilysins combining a polycationic nonapeptide and a modular endolysin are able to kill these (multidrug-resistant) strains in vitro with a 4 to 5 log reduction within 30 min. We show that the activity of Artilysins can be further enhanced by the presence of a linker of increasing length between the peptide and endolysin or by a combination of both polycationic and hydrophobic/amphipathic peptides. Time-lapse microscopy confirmed the mode of action of polycationic Artilysins, showing that they pass the outer membrane to degrade the peptidoglycan with subsequent cell lysis. Artilysins are effective in vitro (human keratinocytes) and in vivo (Caenorhabditis elegans).M.W. held a predoctoral fellowship of the "Instituut voor aanmoediging van Innovatie door Wetenschap en Technologie in Vlaanderen" (IWT Flanders). Y.B. and M. W. were supported by IWT Flanders and Y.B. by a postdoctoral fellowship of the "Bijzonder Onderzoeksfonds-KU Leuven." S. M. is an employee of Lisando GmbH. R. L. acts as scientific adviser to Lisando GmbH

Lysozyme activity of the Ruminococcus champanellensis cellulosome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135571/1/emi13501.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135571/2/emi13501_am.pd

Predicting Risk for Death from MRSA Bacteremia1

Methicillin-resistant Staphylococcus aureus (MRSA) in the bloodstream is often fatal. Vancomycin is the most frequently prescribed drug for treatment of MRSA infections with demonstrated efficacy. Recently, however, some MRSA infections have not been responding to vancomycin, even those caused by strains considered susceptible. To provide optimal treatment and avoid vancomycin resistance, therapy should be tailored, especially for patients at highest risk for death. But who are these patients? A study that looked back at medical records and 699 frozen isolates found that risk for death from MRSA infection was highest among certain populations, including the elderly, nursing home residents, patients with severe sepsis, and patients with liver or kidney disease. Risk for death was not affected by the type of MRSA strain (vancomycin susceptible, heteroresistant, or intermediate resistant). Risk was lower among those who had consulted an infectious disease specialist. Thus, when choosing treatment for patients with MRSA infection, it is crucial to look at patient risk factors, not just MRSA strain type. For those at high risk, consultation with an infectious disease specialist is recommended

Panel 4 : Report of the Microbiology Panel

Objective. To perform a comprehensive review of the literature from July 2011 until June 2015 on the virology and bacteriology of otitis media in children. Data Sources. PubMed database of the National Library of Medicine. Review Methods. Two subpanels comprising experts in the virology and bacteriology of otitis media were created. Each panel reviewed the relevant literature in the fields of virology and bacteriology and generated draft reviews. These initial reviews were distributed to all panel members prior to meeting together at the Post-symposium Research Conference of the 18th International Symposium on Recent Advances in Otitis Media, National Harbor, Maryland, in June 2015. A final draft was created, circulated, and approved by all panel members. Conclusions. Excellent progress has been made in the past 4 years in advancing our understanding of the microbiology of otitis media. Numerous advances were made in basic laboratory studies, in animal models of otitis media, in better understanding the epidemiology of disease, and in clinical practice. Implications for Practice. (1) Many viruses cause acute otitis media without bacterial coinfection, and such cases do not require antibiotic treatment. (2) When respiratory syncytial virus, metapneumovirus, and influenza virus peak in the community, practitioners can expect to see an increase in clinical otitis media cases. (3) Biomarkers that predict which children with upper respiratory tract infections will develop otitis media may be available in the future. (4) Compounds that target newly identified bacterial virulence determinants may be available as future treatment options for children with otitis media.Peer reviewe