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.

Lab Affiliations


All Publications


  • Re-assessing thermal response of schistosomiasis transmission risk: Evidence for a higher thermal optimum than previously predicted. PLoS neglected tropical diseases Aslan, I. H., Pourtois, J. D., Chamberlin, A. J., Mitchell, K. R., Mari, L., Lwiza, K. M., Wood, C. L., Mordecai, E. A., Yu, A., Tuan, R., Palasio, R. G., Monteiro, A. M., Kirk, D., Athni, T. S., Sokolow, S. H., N'Goran, E. K., Diakite, N. R., Ouattara, M., Gatto, M., Casagrandi, R., Little, D. C., Ozretich, R. W., Norman, R., Allan, F., Brierley, A. S., Liu, P., Pereira, T. A., De Leo, G. A. 2024; 18 (6): e0011836

    Abstract

    The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7°C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3°C and 23.6-27.9°C (95% CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.

    View details for DOI 10.1371/journal.pntd.0011836

    View details for PubMedID 38857289

  • Targeted deletion of Pf prophages from diverse Pseudomonas aeruginosa isolates has differential impacts on quorum sensing and virulence traits. Journal of bacteriology Schmidt, A. K., Schwartzkopf, C. M., Pourtois, J. D., Burgener, E. B., Faith, D. R., Joyce, A., Lamma, T., Kumar, G., Bollyky, P. L., Secor, P. R. 2024: e0040223

    Abstract

    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 virulence phenotypes. Most work on Pf phages has focused on Pf4 and its host P. aeruginosa PAO1. Expanding from Pf4 and PAO1, this study explores diverse Pf phages 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. The pflM gene shows diversity among different Pf phage isolates; however, all examined pflM alleles encode the DUF5447 domain. We demonstrate that pflM deletion results in prophage excision but not replication, leading to total prophage loss, indicating a role for lysis/lysogeny decisions for the DUF5447 domain. This study also assesses the effects different Pf phages have on host quorum sensing, biofilm formation, pigment production, and virulence against the bacterivorous nematode Caenorhabditis elegans. We find that Pf phages have strain-specific impacts on quorum sensing and biofilm formation, but nearly all suppress pigment production and increase C. elegans avoidance behavior. 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.IMPORTANCEPseudomonas aeruginosa is an opportunistic bacterial pathogen that is frequently infected by filamentous Pf phages (viruses) that integrate into its chromosome, affecting behavior. Although prior work has focused on Pf4 and PAO1, this study investigates diverse Pf in clinical isolates. A simple method targeting the deletion of the Pf lysogeny maintenance gene pflM (PA0718) effectively eliminates Pf prophages from clinical isolates. The research evaluates the impact Pf prophages have on bacterial quorum sensing, biofilm formation, and virulence phenotypes. This work introduces a valuable tool to eliminate Pf prophages from clinical isolates and advances our understanding of P. aeruginosa and filamentous Pf phage interactions.

    View details for DOI 10.1128/jb.00402-23

    View details for PubMedID 38687034

  • Rapid assessment of changes in phage bioactivity using dynamic light scattering. PNAS nexus Dharmaraj, T., Kratochvil, M. J., Pourtois, J. D., Chen, Q., Hajfathalian, M., Hargil, A., Lin, Y. H., Evans, Z., Oromí-Bosch, A., Berry, J. D., McBride, R., Haddock, N. L., Holman, D. R., van Belleghem, J. D., Chang, T. H., Barr, J. J., Lavigne, R., Heilshorn, S. C., Blankenberg, F. G., Bollyky, P. L. 2023; 2 (12): pgad406

    Abstract

    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. In this study, 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-y-old archival stocks, and evaluate phage samples for use in a phage therapy/wound infection model. We also provide a web application (Phage-Estimator of Lytic Function) to facilitate DLS studies of phages. We conclude that DLS provides a rapid, convenient, and nondestructive tool for quality control of phage preparations in academic and commercial settings.

    View details for DOI 10.1093/pnasnexus/pgad406

    View details for PubMedID 38111822

    View details for PubMedCentralID PMC10726995

  • Illegal deforestation rates were lower during the COVID-19 pandemic in rural Bornean communities with health and livelihood support Hopkins, S., Hazel, A., Pourtois, J., Chamberlin, A., Gajewski, Z., Harryman, I., Sokolow, S., MacDonald, A., Nova, N., Ahmad, A., Andiani, J., Emerson, A., Febriani, N., Finley, N., Miller, A., Sartika, I., Webb, K., Siregar, I., Setiawan, Y., Jones, I., Liu, Z., Burza, S., De Leo, G. WILEY. 2023: 74-75
  • 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 Pourtois, J. D., Tallam, K., Jones, I., Hyde, E., Chamberlin, A. J., Evans, M. V., Ihantamalala, F. A., Cordier, L. F., Razafinjato, B. R., Rakotonanahary, R. J., Tsirinomen'ny Aina, A., Soloniaina, P., Raholiarimanana, S. H., Razafinjato, C., Bonds, M. H., De Leo, G. A., Sokolow, S. H., Garchitorena, A. 2023; 3 (2): e0001607

    Abstract

    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 Pourtois, J. D., Provost, M. M., Micheli, F., De Leo, G. A. 2022
  • Filamentous Bacteriophages and the Competitive Interaction between Pseudomonas aeruginosa Strains under Antibiotic Treatment: a Modeling Study. mSystems Pourtois, J. D., Kratochvil, M. J., Chen, Q., Haddock, N. L., Burgener, E. B., De Leo, G. A., Bollyky, P. L. 2021: e0019321

    Abstract

    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 Secor, P. R., Burgener, E. B., Kinnersley, M. n., Jennings, L. K., Roman-Cruz, V. n., Popescu, M. n., Van Belleghem, J. D., Haddock, N. n., Copeland, C. n., Michaels, L. A., de Vries, C. R., Chen, Q. n., Pourtois, J. n., Wheeler, T. J., Milla, C. E., Bollyky, P. L. 2020; 11: 244

    Abstract

    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 Pourtois, J., Tarnita, C. E., Bonachela, J. A. 2020; 11: 221

    Abstract

    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