Current Research and Scholarly Interests
My research focuses on how environmental conditions affect the interaction between bacteriophages and their bacterial hosts, and their impact on disease. I use mathematical models, and collaborate with lab and field researchers to inform my models. My current study systems include bacterial infections in the lung of patients with cystic fibrosis, and abalone withering syndrome.
Giulio De Leo, De Leo Lab (9/1/2020)
Targeted deletion of Pf prophages from diversePseudomonas aeruginosaisolates impacts quorum sensing and virulence traits.
bioRxiv : the preprint server for biology
Pseudomonas aeruginosa is an opportunistic bacterial pathogen that commonly causes medical hardware, wound, and respiratory infections. Temperate filamentous Pf phages that infect P. aeruginosa impact numerous bacterial virulence phenotypes. Most work on Pf phages has focused on strain Pf4 and its host P. aeruginosa PAO1. Expanding from Pf4 and PAO1, this study explores diverse Pf strains infecting P. aeruginosa clinical isolates. We describe a simple technique targeting the Pf lysogeny maintenance gene, pflM (PA0718), that enables the effective elimination of Pf prophages from diverse P. aeruginosa hosts. This study also assesses the effects different Pf phages have on host quorum sensing, biofilm formation, virulence factor production, and virulence. Collectively, this research not only introduces a valuable tool for Pf prophage elimination from diverse P. aeruginosa isolates, but also advances our understanding of the complex relationship between P. aeruginosa and filamentous Pf phages.
View details for DOI 10.1101/2023.11.19.567716
View details for PubMedID 38014273
Rapid assessment of changes in phage bioactivity using dynamic light scattering.
bioRxiv : the preprint server for biology
Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity. We then use DLS to optimize phage storage conditions for phages from human clinical trials, predict bioactivity in 50-year-old archival stocks, and evaluate phage samples for use in a phage therapy/wound infection model. We also provide a web-application (Phage-ELF) to facilitate DLS studies of phages. We conclude that DLS provides a rapid, convenient, and non-destructive tool for quality control of phage preparations in academic and commercial settings.
View details for DOI 10.1101/2023.07.02.547396
View details for PubMedID 37425882
View details for PubMedCentralID PMC10327207
Climatic, land-use and socio-economic factors can predict malaria dynamics at fine spatial scales relevant to local health actors: Evidence from rural Madagascar.
PLOS global public health
2023; 3 (2): e0001607
While much progress has been achieved over the last decades, malaria surveillance and control remain a challenge in countries with limited health care access and resources. High-resolution predictions of malaria incidence using routine surveillance data could represent a powerful tool to health practitioners by targeting malaria control activities where and when they are most needed. Here, we investigate the predictors of spatio-temporal malaria dynamics in rural Madagascar, estimated from facility-based passive surveillance data. Specifically, this study integrates climate, land-use, and representative household survey data to explain and predict malaria dynamics at a high spatial resolution (i.e., by Fokontany, a cluster of villages) relevant to health care practitioners. Combining generalized linear mixed models (GLMM) and path analyses, we found that socio-economic, land use and climatic variables are all important predictors of monthly malaria incidence at fine spatial scales, via both direct and indirect effects. In addition, out-of-sample predictions from our model were able to identify 58% of the Fokontany in the top quintile for malaria incidence and account for 77% of the variation in the Fokontany incidence rank. These results suggest that it is possible to build a predictive framework using environmental and social predictors that can be complementary to standard surveillance systems and help inform control strategies by field actors at local scales.
View details for DOI 10.1371/journal.pgph.0001607
View details for PubMedID 36963091
View details for PubMedCentralID PMC10021226
- Modelling the effect of habitat and fishing heterogeneity on the performance of a Total Allowable Catch-regulated fishery ICES JOURNAL OF MARINE SCIENCE 2022
Filamentous Bacteriophages and the Competitive Interaction between Pseudomonas aeruginosa Strains under Antibiotic Treatment: a Modeling Study.
Pseudomonas aeruginosa (Pa) is a major bacterial pathogen responsible for chronic lung infections in cystic fibrosis patients. Recent work has implicated Pf bacteriophages, nonlytic filamentous viruses produced by Pa, in the chronicity and severity of Pa infections. Pf phages act as structural elements in Pa biofilms and sequester aerosolized antibiotics, thereby contributing to antibiotic tolerance. Consistent with a selective advantage in this setting, the prevalence of Pf-positive (Pf+) bacteria increases over time in these patients. However, the production of Pf phages comes at a metabolic cost to bacteria, such that Pf+ strains grow more slowly than Pf-negative (Pf-) strains in vitro. Here, we use a mathematical model to investigate how these competing pressures might influence the relative abundance of Pf+ versus Pf- strains in different settings. Our model suggests that Pf+ strains of Pa cannot outcompete Pf- strains if the benefits of phage production falls onto both Pf+ and Pf- strains for a majority of parameter combinations. Further, phage production leads to a net positive gain in fitness only at antibiotic concentrations slightly above the MIC (i.e., concentrations for which the benefits of antibiotic sequestration outweigh the metabolic cost of phage production) but which are not lethal for Pf+ strains. As a result, our model suggests that frequent administration of intermediate doses of antibiotics with low decay rates and high killing rates favors Pf+ over Pf- strains. These models inform our understanding of the ecology of Pf phages and suggest potential treatment strategies for Pf+ Pa infections. IMPORTANCE Filamentous phages are a frontier in bacterial pathogenesis, but the impact of these phages on bacterial fitness is unclear. In particular, Pf phages produced by Pa promote antibiotic tolerance but are metabolically expensive to produce, suggesting that competing pressures may influence the prevalence of Pf+ versus Pf- strains of Pa in different settings. Our results identify conditions likely to favor Pf+ strains and thus antibiotic tolerance. This study contributes to a better understanding of the unique ecology of filamentous phages in both environmental and clinical settings and may facilitate improved treatment strategies for combating antibiotic tolerance.
View details for DOI 10.1128/mSystems.00193-21
View details for PubMedID 34156288
Pf Bacteriophage and Their Impact on Pseudomonas Virulence, Mammalian Immunity, and Chronic Infections.
Frontiers in immunology
2020; 11: 244
Pf bacteriophage are temperate phages that infect the bacterium Pseudomonas aeruginosa, a major cause of chronic lung infections in cystic fibrosis (CF) and other settings. Pf and other temperate phages have evolved complex, mutualistic relationships with their bacterial hosts that impact both bacterial phenotypes and chronic infection. We and others have reported that Pf phages are a virulence factor that promote the pathogenesis of P. aeruginosa infections in animal models and are associated with worse skin and lung infections in humans. Here we review the biology of Pf phage and what is known about its contributions to pathogenesis and clinical disease. First, we review the structure, genetics, and epidemiology of Pf phage. Next, we address the diverse and surprising ways that Pf phages contribute to P. aeruginosa phenotypes including effects on biofilm formation, antibiotic resistance, and motility. Then, we cover data indicating that Pf phages suppress mammalian immunity at sites of bacterial infection. Finally, we discuss recent literature implicating Pf in chronic P. aeruginosa infections in CF and other settings. Together, these reports suggest that Pf bacteriophage have direct effects on P. aeruginosa infections and that temperate phages are an exciting frontier in microbiology, immunology, and human health.
View details for DOI 10.3389/fimmu.2020.00244
View details for PubMedID 32153575
View details for PubMedCentralID PMC7047154
Impact of Lytic Phages on Phosphorus- vs. Nitrogen-Limited Marine Microbes.
Frontiers in microbiology
2020; 11: 221
Lytic viruses kill almost 20% of marine bacteria every day, re-routing nutrients away from the higher trophic levels of the marine food web and back in the microbial loop. Importantly, the effect of this inflow of key elements on the ecosystem depends on the nutrient requirements of bacteria as well as on the elemental composition of the viruses that infect them. Therefore, the influence of viruses on the ecosystem could vary depending on which nutrient is limiting. In this paper, we considered an existing multitrophic model (nutrient, bacteria, zooplankton, and viruses) that accounts for nitrogen limitation, and developed a phosphorus-limited version to assess whether the limiting nutrient alters the role of viruses in the ecosystem. For both versions, we evaluated the stationary state of the system with and without viruses. In agreement with existing results, nutrient release increased with viruses for nitrogen-limited systems, while zooplankton abundance and export to higher trophic levels decreased. We found this to be true also for phosphorus-limited systems, although nutrient release increased less than in nitrogen-limited systems. The latter supports a nutrient-specific response of the ecosystem to viruses. Bacterial concentration decreased in the phosphorus-limited system but increased in most nitrogen-limited cases due to a switch from mostly bottom-up to entirely top-down control by viruses. Our results also show that viral concentration is best predicted by a power-law of bacterial concentration with exponent different from 1. Finally, we found a positive correlation between carbon export and viruses regardless of the limiting nutrient, which led us to suggest viral abundance as a predictor of carbon sink.
View details for DOI 10.3389/fmicb.2020.00221
View details for PubMedID 32153528