Phage therapy: An alternative to antibiotics in the age of multi-drug resistance.

The practice of phage therapy, which uses bacterial viruses (phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins, specifically against multidrug-resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage- or antibiotic-based, each have relative advantages and disadvantages; accordingly, many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infections. Although much is still unknown about the interactions between phage, bacteria, and human host, the time to take phage therapy seriously seems to be rapidly approaching

Course-based Science Research Promotes Learning in Diverse Students at Diverse Institutions

Course-based research experiences (CREs) are powerful strategies for spreading learning and improving persistence for all students, both science majors and nonscience majors. Here we address the crucial components of CREs (context, discovery, ownership, iteration, communication, presentation) found across a broad range of such courses at a variety of academic institutions. We also address how the design of a CRE should vary according to the background of student participants; no single CRE format is perfect. We provide a framework for implementing CREs across multiple institutional types and several disciplines throughout the typical four years of undergraduate work, designed to a variety of student backgrounds. Our experiences implementing CREs also provide guidance on overcoming barriers to their implementation

Experimental phage therapy of burn wound infection : difficult first steps

Antibiotic resistance has become a major public health problem and the antibiotics pipeline is running dry. Bacteriophages (phages) may offer an ‘innovative’ means of infection treatment, which can be combined or alternated with antibiotic therapy and may enhance our abilities to treat bacterial infections successfully. Today, in the Queen Astrid Military Hospital, phage therapy is increasingly considered as part of a salvage therapy for patients in therapeutic dead end, particularly those with multidrug resistant infections. We describe the application of a well-defined and quality controlled phage cocktail, active against Pseudomonas aeruginosa and Staphylococcus aureus, on colonized burn wounds within a modest clinical trial (nine patients, 10 applications), which was approved by a leading Belgian Medical Ethical Committee. No adverse events, clinical abnormalities or changes in laboratory test results that could be related to the application of phages were observed. Unfortunately, this very prudent ‘clinical trial’ did not allow for an adequate evaluation of the efficacy of the phage cocktail. Nevertheless, this first ‘baby step’ revealed several pitfalls and lessons for future experimental phage therapy and helped overcome the psychological hurdles that existed to the use of viruses in the treatment of patients in our burn unit

Improved single-swab sample preparation for recovering bacterial and phage DNA from human skin and wound microbiomes.

BackgroundCharacterization of the skin and wound microbiome is of high biomedical interest, but is hampered by the low biomass of typical samples. While sample preparation from other microbiomes (e.g., gut) has been the subject of extensive optimization, procedures for skin and wound microbiomes have received relatively little attention. Here we describe an improved method for obtaining both phage and microbial DNA from a single skin or wound swab, characterize the yield of DNA in model samples, and demonstrate the utility of this approach with samples collected from a wound clinic.ResultsWe find a substantial improvement when processing wound samples in particular; while only one-quarter of wound samples processed by a traditional method yielded sufficient DNA for downstream analysis, all samples processed using the improved method yielded sufficient DNA. Moreover, for both skin and wound samples, community analysis and viral reads obtained through deep sequencing of clinical swab samples showed significant improvement with the use of the improved method.ConclusionUse of this method may increase the efficiency and data quality of microbiome studies from low-biomass samples

Molecular bases and role of viruses in the human microbiome.

Viruses are dependent biological entities that interact with the genetic material of most cells on the planet, including the trillions within the human microbiome. Their tremendous diversity renders analysis of human viral communities ("viromes") to be highly complex. Because many of the viruses in humans are bacteriophage, their dynamic interactions with their cellular hosts add greatly to the complexities observed in examining human microbial ecosystems. We are only beginning to be able to study human viral communities on a large scale, mostly as a result of recent and continued advancements in sequencing and bioinformatic technologies. Bacteriophage community diversity in humans not only is inexorably linked to the diversity of their cellular hosts but also is due to their rapid evolution, horizontal gene transfers, and intimate interactions with host nucleic acids. There are vast numbers of observed viral genotypes on many body surfaces studied, including the oral, gastrointestinal, and respiratory tracts, and even in the human bloodstream, which previously was considered a purely sterile environment. The presence of viruses in blood suggests that virome members can traverse mucosal barriers, as indeed these communities are substantially altered when mucosal defenses are weakened. Perhaps the most interesting aspect of human viral communities is the extent to which they can carry gene functions involved in the pathogenesis of their hosts, particularly antibiotic resistance. Persons in close contact with each other have been shown to share a fraction of oral virobiota, which could potentially have important implications for the spread of antibiotic resistance to healthy individuals. Because viruses can have a large impact on ecosystem dynamics through mechanisms such as the transfers of beneficial gene functions or the lysis of certain populations of cellular hosts, they may have both beneficial and detrimental roles that affect human health, including improvements in microbial resilience to disturbances, immune evasion, maintenance of physiologic processes, and altering the microbial community in ways that promote or prevent pathogen colonization

Modeling, Simulation and Application of Bacterial Transduction in Genetic Algorithms

At present, all methods in Evolutionary Computation are bioinspired in the fundamental principles of neo-Darwinism as well as on a vertical gene transfer. Thus, on a mechanism in which an organism receives genetic material from its ancestor. Horizontal, lateral or cross-population gene transfer is any process in which an organism transfers a genetic segment to another one that is not its offspring. Virus transduction is one of the key mechanisms of horizontal gene propagation in microorganism (e.g. bacteria). In the present paper, we model and simulate a transduction operator, exploring a possible role and usefulness of transduction in a genetic algorithm. The genetic algorithm including transduction has been named PETRI (abbreviation of Promoting Evolution Through Reiterated Infection). The efficiency and performance of this algorithm was evaluated using a benchmark function and the 0/1 knapsack problem. The utility was illustrated designing an AM radio receiver, optimizing the main features of the electronic components of the AM radio circuit as well as those of the radio enclosure. Our results shown how PETRI approaches to higher fitness values as transduction probability comes near to 100%. The conclusion is that transduction improves the performance of a genetic algorithm, assuming a population divided among several sub-populations or ‘bacterial colonies’

Applications of Personalised Phage Therapy highlighting the importance of Bacteriophage Banks against Emerging Antimicrobial Resistance

Emerging antibiotic resistance is one of the most important microbiological issues of the 21st century. This poses a query regarding the future use of antibiotics and availability of other promising therapeutic alternatives. The awareness about antibiotic misuse has improved insufficiently and is evident by the increased incidences of multidrug resistant infections globally. Amongst different antibacterial therapeutic approaches phage therapy has created a niche of its own due to continuous use for treatment of human infections in Eastern Europe. Synergistic compounds along with phages have also been proposed as a better alternative compared to antibiotics or phage alone for treatment of chronic cases and seriously debilitating diseases. As such, why not allow custom made phage therapy for treatment of chronic infections? However, the success of phage therapy will depend upon instant availability of characterised bacteriophages from bacteriophage banks which may serve as the major catalyst in bringing Phage Therapy to main stream treatment alternatives or in combination therapy at least. In the current article we present a glimpse of comprehensive approach about utility of bacteriophage banks and further present personalised phage therapy in a synergistic role with antibiotics to overcome emerging antimicrobial resistance

Data Analysis Recitation Activities Support Better Understanding in SEA-PHAGES CURE

Course-based undergraduate research experiences (CUREs) are widely known to improve student learning outcomes in the sciences. Undergraduate students have a particularly difficult time interpreting the scientific data that they generate in these experiences – especially when lacking opportunity and exposure to science processes prior to entering higher education. Therefore, it is vital to structure these research experiences such that students can see maximal gains in their skills. This is especially true in the SEA-PHAGES (Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science) lab experience, which focuses on bacteriophages – a subject about which most undergraduate students have limited knowledge. In the SEA-PHAGES lab experience at The Ohio State University, we observed that while students made rapid gains in science process skills over the course of the semester, they still struggled to interpret the data they generated. To address this issue, we designed and implemented a set of five recitation activities to complement the lab experience, termed Recitation Activities to Improve Literacy in Science (RAILS). Using an adapted student assessment of learning gains (SALG) survey, we observed that these activities improved students' perceived ability to interpret their data, and students reported that they experienced significant gains in their data analysis ability as a result of the activities. We hope that other SEA-PHAGES instructors will similarly benefit from utilizing these recitation activities as part of their implementation of the curriculum. Primary image: Phages on RAILS. A bacteriophage is pictured driving a train engine down a track

phiSITE: database of gene regulation in bacteriophages

We have developed phiSITE, database of gene regulation in bacteriophages. To date it contains detailed information about more than 700 experimentally confirmed or predicted regulatory elements (promoters, operators, terminators and attachment sites) from 32 bacteriophages belonging to Siphoviridae, Myoviridae and Podoviridae families. The database is manually curated, the data are collected mainly form scientific papers, cross-referenced with other database resources (EMBL, UniProt, NCBI taxonomy database, NCBI Genome, ICTVdb, PubMed Central) and stored in SQL based database system. The system provides full text search for regulatory elements, graphical visualization of phage genomes and several export options. In addition, visualizations of gene regulatory networks for five phages (Bacillus phage GA-1, Enterobacteria phage lambda, Enterobacteria phage Mu, Enterobacteria phage P2 and Mycoplasma phage P1) have been defined and made available. The phiSITE is accessible at http://www.phisite.org/