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1. Computational host range prediction—The good, the bad, and the ugly

   https://doi.org/10.1093/ve/vead083  

   Howell, Abigail A.; Versoza, Cyril J.; Pfeifer, Susanne P. (December 2023, Virus Evolution)

   Abstract The rapid emergence and spread of antimicrobial resistance across the globe have prompted the usage of bacteriophages (i.e. viruses that infect bacteria) in a variety of applications ranging from agriculture to biotechnology and medicine. In order to effectively guide the application of bacteriophages in these multifaceted areas, information about their host ranges—that is the bacterial strains or species that a bacteriophage can successfully infect and kill—is essential. Utilizing sixteen broad-spectrum (polyvalent) bacteriophages with experimentally validated host ranges, we here benchmark the performance of eleven recently developed computational host range prediction tools that provide a promising and highly scalable supplement to traditional, but laborious, experimental procedures. We show that machine- and deep-learning approaches offer the highest levels of accuracy and precision—however, their predominant predictions at the species- or genus-level render them ill-suited for applications outside of an ecosystems metagenomics framework. In contrast, only moderate sensitivity (<80 per cent) could be reached at the strain-level, albeit at low levels of precision (<40 per cent). Taken together, these limitations demonstrate that there remains room for improvement in the active scientific field of in silico host prediction to combat the challenge of guiding experimental designs to identify the most promising bacteriophage candidates for any given application. 

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2. Computational Prediction of Bacteriophage Host Ranges

   https://doi.org/10.3390/microorganisms10010149  

   Versoza, Cyril J.; Pfeifer, Susanne P. (January 2022, Microorganisms)

   Increased antibiotic resistance has prompted the development of bacteriophage agents for a multitude of applications in agriculture, biotechnology, and medicine. A key factor in the choice of agents for these applications is the host range of a bacteriophage, i.e., the bacterial genera, species, and strains a bacteriophage is able to infect. Although experimental explorations of host ranges remain the gold standard, such investigations are inherently limited to a small number of viruses and bacteria amendable to cultivation. Here, we review recently developed bioinformatic tools that offer a promising and high-throughput alternative by computationally predicting the putative host ranges of bacteriophages, including those challenging to grow in laboratory environments. 

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3. Microbacterium Cluster EA Bacteriophages: Phylogenomic Relationships and Host Range Predictions

   https://doi.org/10.3390/microorganisms11010170  

   Milhaven, Mark; Versoza, Cyril J.; Garg, Aman; Cai, Lindsey; Cherian, Sanjana; Johnson, Kamalei; Salas Perez, Kevin; Blanco, Madison; Lobatos, Jackelyn; Mitra, Corinne; et al (January 2023, Microorganisms)

   Bacteriophages are being widely harnessed as an alternative to antibiotics due to the global emergence of drug-resistant pathogens. To guide the usage of these bactericidal agents, characterization of their host specificity is vital—however, host range information remains limited for many bacteriophages. This is particularly the case for bacteriophages infecting the Microbacterium genus, despite their importance in agriculture, biomedicine, and biotechnology. Here, we elucidate the phylogenomic relationships between 125 Microbacterium cluster EA bacteriophages—including members from 11 sub-clusters (EA1 to EA11)—and infer their putative host ranges using insights from codon usage bias patterns as well as predictions from both exploratory and confirmatory computational methods. Our computational analyses suggest that cluster EA bacteriophages have a shared infection history across the Microbacterium clade. Interestingly, bacteriophages of all sub-clusters exhibit codon usage preference patterns that resemble those of bacterial strains different from ones used for isolation, suggesting that they might be able to infect additional hosts. Furthermore, host range predictions indicate that certain sub-clusters may be better suited in prospective biotechnological and medical applications such as phage therapy. 

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4. Biofilm Structure Promotes Coexistence of Phage-Resistant and Phage-Susceptible Bacteria

   https://doi.org/10.1128/mSystems.00877-19  

   Simmons, Emilia L.; Bond, Matthew C.; Koskella, Britt; Drescher, Knut; Bucci, Vanni; Nadell, Carey D. (June 2020, mSystems)

   Bordenstein, Seth (Ed.)

   ABSTRACT Encounters among bacteria and their viral predators (bacteriophages) are among the most common ecological interactions on Earth. These encounters are likely to occur with regularity inside surface-bound communities that microbes most often occupy in natural environments. Such communities, termed biofilms, are spatially constrained: interactions become limited to near neighbors, diffusion of solutes and particulates can be reduced, and there is pronounced heterogeneity in nutrient access and physiological state. It is appreciated from prior theoretical work that phage-bacteria interactions are fundamentally different in spatially structured contexts, as opposed to well-mixed liquid culture. Spatially structured communities are predicted to promote the protection of susceptible host cells from phage exposure, and thus weaken selection for phage resistance. The details and generality of this prediction in realistic biofilm environments, however, are not known. Here, we explore phage-host interactions using experiments and simulations that are tuned to represent the essential elements of biofilm communities. Our simulations show that in biofilms, phage-resistant cells—as their relative abundance increases—can protect clusters of susceptible cells from phage exposure, promoting the coexistence of susceptible and phage-resistant bacteria under a large array of conditions. We characterize the population dynamics underlying this coexistence, and we show that coexistence is recapitulated in an experimental model of biofilm growth measured with confocal microscopy. Our results provide a clear view into the dynamics of phage resistance in biofilms with single-cell resolution of the underlying cell-virion interactions, linking the predictions of canonical theory to realistic models and in vitro experiments of biofilm growth. IMPORTANCE In the natural environment, bacteria most often live in communities bound to one another by secreted adhesives. These communities, or biofilms, play a central role in biogeochemical cycling, microbiome functioning, wastewater treatment, and disease. Wherever there are bacteria, there are also viruses that attack them, called phages. Interactions between bacteria and phages are likely to occur ubiquitously in biofilms. We show here, using simulations and experiments, that biofilms will in most conditions allow phage-susceptible bacteria to be protected from phage exposure, if they are growing alongside other cells that are phage resistant. This result has implications for the fundamental ecology of phage-bacteria interactions, as well as the development of phage-based antimicrobial therapeutics. 

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5. Emerging investigator series: the role of phage lifestyle in wastewater microbial community structures and functions: insights into diverse microbial environments

   https://doi.org/10.1039/D2EW00755J  

   Delgado Vela, Jeseth; Al-Faliti, Mitham (January 2023, Environmental Science: Water Research & Technology)

   For over a century, environmental engineers have attempted to control the prokaryotic community biological wastewater treatment processes, but there is growing interest in both understanding and harnessing the activity of phages in wastewater bioprocesses. While phages are known to be present and abundant, their ecological role, potential benefits, and impacts on wastewater biological processes are not fully understood. Fundamental knowledge on how phages infect host cells from relatively simple pure culture studies alongside environmental studies from marine and soil systems can be used to predict the potential impact of phages in diverse and dynamic wastewater environments. This frontier review is focused on what is known about the molecular mechanisms by which phages infect bacteria and how that could apply to biological process control and operation within wastewater treatment systems. Here, we specifically focus on highlights from studies on the molecular mechanisms that drive lysis and lysogeny within phage cells and the impacts on the dissemination of antibiotic resistance genes and nutrient removal within a biological wastewater process. 

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