A5019444422- Evolution and Genetic Dynamics
- Bacteriophages and microbial interactions
- Plant Virus Research Studies
- Mathematical and Theoretical Epidemiology and Ecology Models
- Evolutionary Game Theory and Cooperation
- Genomics and Phylogenetic Studies
- Viral Infections and Vectors
- Microbial infections and disease research
- Mosquito-borne diseases and control
- Bacterial Genetics and Biotechnology
- Animal Virus Infections Studies
- Respiratory viral infections research
- Animal Disease Management and Epidemiology
- Insect symbiosis and bacterial influences
- Cystic Fibrosis Research Advances
- Vibrio bacteria research studies
- Innovation and Knowledge Management
- Plant and Fungal Interactions Research
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Zoonotic diseases and public health
- Viral gastroenteritis research and epidemiology
- Antibiotic Resistance in Bacteria
- Virology and Viral Diseases
- Plant and animal studies
Yale University
2015-2024
United States Geological Survey
2024
University of Wisconsin–Madison
2024
Quantitative BioSciences
2023-2024
Whitney Museum of American Art
2024
University of New Haven
2023
Michigan State University
1997-2021
Leeds Beckett University
2018-2021
Google (United States)
2015
San Francisco Department of Public Health
2013
Abstract Increasing prevalence and severity of multi-drug-resistant (MDR) bacterial infections has necessitated novel antibacterial strategies. Ideally, new approaches would target pathogens while exerting selection for reduced pathogenesis when these bacteria inevitably evolve resistance to therapeutic intervention. As an example such a management strategy, we isolated lytic bacteriophage, OMKO1, (family Myoviridae ) Pseudomonas aeruginosa that utilizes the outer membrane porin M (OprM)...
Management of prosthetic vascular graft infections caused by Pseudomonas aeruginosa can be a significant challenge to clinicians. These often do not resolve with antibiotic therapy alone due resistance/tolerance bacteria, poor ability antibiotics permeate/reduce biofilms and/or other factors. Bacteriophage OMKO1 binding efflux pump proteins in P. was consistent an evolutionary trade-off: wildtype bacteria were killed phage whereas evolution phage-resistance led increased sensitivity....
Significance Rhinovirus is the most frequent cause of common cold, as well one important causes asthma exacerbations. Most rhinovirus strains replicate better at cooler temperatures found in nasal cavity than lung temperature, but underlying mechanisms are not known. Using a mouse-adapted virus, we that airway epithelial cells supporting replication initiate more robust antiviral defense response through RIG-I–like receptor (RLR)–dependent interferon secretion and enhanced responsiveness...
Bacteria frequently encounter selection by both antibiotics and lytic bacteriophages. However, the evolutionary interactions between phages remain unclear, in particular, whether when can drive trade-offs with antibiotic resistance. Here, we describe Escherichia coli phage U136B, showing it relies on two host factors involved different resistance mechanisms: 1) efflux pump protein TolC 2) structural barrier molecule lipopolysaccharide (LPS). Since LPS contribute to resistance, U136B should...
Abstract Although host radiation allows a parasite to expand its ecological niche, traits governing the infection of multiple types can decrease fitness in original or alternate environments. Reasons for this reduction include slower replication due added genetic material modifications, trade-offs across environments, and weaker selection resulting from simultaneous adaptation habitats. We examined consequences using vesicular stomatitis virus (VSV) mammalian cells tissue culture. Replicate...
Natural and experimental systems have failed to universally demonstrate a trade-off between generalism specialism. When does occur it is difficult attribute its cause antagonistic pleiotropy without dissecting the genetic basis of adaptation, few previous experiments provide these data. Here we investigate evolution expanded host range (generalism) in RNA virus phi6, an model system allowing adaptive mutations be readily identified. We isolated 10 spontaneous mutants on each three novel...
A series of competition experiments with two genotypes Escherichia coli showed that each genotype was favored when it the minority, allowing their coexistence in a stable polymorphism. In these experiments, glucose sole source carbon provided, and its concentration limiting to population density. Thus, polymorphism did not conform simple model competitive exclusion. similar also as resource, we considered hypotheses might explain observed coexistence: (1) strictly demographic trade—off, such...
Significance Bacteriophages (phages), viruses that infect bacteria, are the most abundant microbes on Earth. Extreme specificity to host species or even strains of bacteria makes phages amenable particular biotechnical applications. This is partially governed by surface-expressed structures use as cell-binding receptors. However, these receptors remain less-studied in phage biology, because their discovery relies laborious methods utilizing well-characterized bacteria. Here we present INSeq...
The spread of multidrug-resistant (MDR) bacteria is a global public health crisis. Bacteriophage therapy (or "phage therapy") constitutes potential alternative approach to treat MDR infections. However, the effective use phage may be limited when phage-resistant bacterial mutants evolve and proliferate during treatment. Here, we develop nonlinear population dynamics model combination that accounts for system-level interactions between bacteria, phage, antibiotics in vivo application given an...
Antimicrobial resistance is a growing global concern and has spurred increasing efforts to find alternative therapeutics. Bacteriophage therapy seen near constant use in Eastern Europe since its discovery over century ago. One promising approach phages that not only reduce bacterial pathogen loads but also select for phage mechanisms trade-off with antibiotic resistance-so called 'phage steering'.Recent work shown the OMKO1 can interact efflux pumps so doing both sensitivity of pathogenic...
Abstract Pseudomonas aeruginosa and Staphylococcus aureus are bacterial pathogens frequently associated with pulmonary complications disease progression in cystic fibrosis (CF). However, these bacteria increasingly show resistance to antibiotics, necessitating novel management strategies. One possibility is bacteriophage (phages; bacteria‐specific viruses) therapy, where lytic phages administered kill target pathogens. Recent publications of case reports phage therapy treat...
Evolutionary medicine – i.e. the application of insights from evolution and ecology to biomedicine has tremendous untapped potential spark transformational innovation in biomedical research, clinical care public health. Fundamentally, a systematic mapping across full diversity life is required identify animal model systems for disease vulnerability, resistance, counter-resistance that could lead novel treatments. dynamics should guide therapeutic approaches target development treatment...
Abstract Bacteriophage therapy is one potential strategy to treat antimicrobial resistant or persistent bacterial infections, and the year 2021 marked centennial of Felix d’Hérelle’s first publication on clinical applications phages. At Center for Phage Biology & Therapy at Yale University, a preparatory modular approach has been established offer safe potent phages single-patient investigational new drug while recognizing time constraints imposed by infection(s). This study provides...
It has been hypothesized that there is a fundamental conflict between horizontal (infectious) and vertical (intergenerational) modes of parasite transmission. Activities increase its rate infectious transmission are presumed to reduce host's fitness. This reduction in host fitness impedes the causes tradeoff Given this tradeoff, assuming no multiple infections (no within-host competition among parasites), simple model predicts density uninfected hosts environment should determine optimum...
Abstract Sex allows beneficial mutations that occur in separate lineages to be fixed the same genome. For this reason, Fisher-Muller model predicts adaptation environment is more rapid a large sexual population than an equally asexual population. Sexual reproduction occurs populations of RNA virus φ6 when multiple bacteriophages coinfect host cell. Here, we tested model's predictions by determining whether sex favors bacterial host, Pseudomonas phaseolicola. Replicate were allowed evolve...
Mutational (genetic) robustness is phenotypic constancy in the face of mutational changes to genome. Robustness critical understanding evolution because phenotypically expressed genetic variation fuel natural selection. Nonetheless, evidence for adaptive biological populations controversial. should be selectively favored when mutation rates are high, a common feature RNA viruses. However, selection may relaxed under virus co-infection complementation between genotypes can buffer effects. We...
We previously examined competitive interactions among viruses by allowing the RNA phage Φ6 to evolve at high and low multiplicities of infection (ratio infecting bacterial cells). Derived high‐multiplicity phages were competitively advantaged relative their ancestors during coinfection, but fixation caused population fitness decline. These data conform evolution lowered in a defectors, as expected from Prisoner's Dilemma game theory. However, generality this result is unknown; other may...