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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. More’s the Same—Multiple Hosts Do Not Select for Broader Host Range Phages

   https://doi.org/10.3390/v15020518  

   Myers, Jupiter; Davis II, Joshua; Lollo, Megan; Hudec, Gabriella; Hyman, Paul (February 2023, Viruses)

   Bacteriophage host range is a result of the interactions between phages and their hosts. For phage therapy, phages with a broader host range are desired so that a phage can infect and kill the broadest range of pathogen strains or related species possible. A common, but not well-tested, belief is that using multiple hosts during the phage isolation will make the isolation of broader host range phage more likely. Using a Bacillus cereus group system, we compared the host ranges of phages isolated on one or four hosts and found that there was no difference in the breadth of host ranges of the isolated phages. Both narrow and broader host range phage were also equally likely to be isolated from either isolation procedure. While there are methods that reliably isolate broader host range phages, such as sequential host isolation, and there are other reasons to use multiple hosts during isolation, multiple hosts are not a consistent way to obtain broader host range phages. 

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3. Comparative Genomics of Closely-Related Gordonia Cluster DR Bacteriophages

   https://doi.org/10.3390/v14081647  

   Versoza, Cyril J.; Howell, Abigail A.; Aftab, Tanya; Blanco, Madison; Brar, Akarshi; Chaffee, Elaine; Howell, Nicholas; Leach, Willow; Lobatos, Jackelyn; Luca, Michael; et al (August 2022, Viruses)

   Bacteriophages infecting bacteria of the genus Gordonia have increasingly gained interest in the scientific community for their diverse applications in agriculture, biotechnology, and medicine, ranging from biocontrol agents in wastewater management to the treatment of opportunistic pathogens in pulmonary disease patients. However, due to the time and costs associated with experimental isolation and cultivation, host ranges for many bacteriophages remain poorly characterized, hindering a more efficient usage of bacteriophages in these areas. Here, we perform a series of computational genomic inferences to predict the putative host ranges of all Gordonia cluster DR bacteriophages known to date. Our analyses suggest that BiggityBass (as well as several of its close relatives) is likely able to infect host bacteria from a wide range of genera—from Gordonia to Nocardia to Rhodococcus, making it a suitable candidate for future phage therapy and wastewater treatment strategies. 

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4. 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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5. Experimental evolution for niche breadth in bacteriophage T4 highlights the importance of structural genes

   https://doi.org/10.1002/mbo3.968  

   Pham, Jenny Y.; Ogbunugafor, C. Brandon; Nguyen Ba, Alex N.; Hartl, Daniel L. (November 2019, MicrobiologyOpen)

   Abstract Ecologists have long studied the evolution of niche breadth, including how variability in environments can drive the evolution of specialism and generalism. This concept is of particular interest in viruses, where niche breadth evolution may explain viral disease emergence, or underlie the potential for therapeutic measures like phage therapy. Despite the significance and potential applications of virus–host interactions, the genetic determinants of niche breadth evolution remain underexplored in many bacteriophages. In this study, we present the results of an evolution experiment with a model bacteriophage system,Escherichia virus T4,in several host environments: exposure toEscherichia coliC, exposure toE. coliK‐12, and exposure to bothE. coliC andE. coliK‐12. This experimental framework allowed us to investigate the phenotypic and molecular manifestations of niche breadth evolution. First, we show that selection on different hosts led to measurable changes in phage productivity in all experimental populations. Second, whole—genome sequencing of experimental populations revealed signatures of selection. Finally, clear and consistent patterns emerged across the host environments, especially the presence of new mutations in phage structural genes—genes encoding proteins that provide morphological and biophysical integrity to a virus. A comparison of mutations found across functional gene categories revealed that structural genes acquired significantly more mutations than other categories. Our findings suggest that structural genes are central determinants in bacteriophage niche breadth. 

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