Digital phagograms: predicting phage infectivity through a multilayer machine learning approach

Lood, Cédric; Boeckaerts, Dimitri; Stock, Michiel; Baets, Bernard De; Lavigne, Rob; Noort, Vera van; Briers, Yves

doi:10.1016/j.coviro.2021.12.004

Cited by 32 publications

(20 citation statements)

References 87 publications

(45 reference statements)

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“…Our results hint at the possibility of predicting phage capsular tropism only from depolymerase sequence information, a goal that we achieved partially and that should be further addressed in the future. Machine-learning approaches (Boeckaerts et al, 2021; Lood et al, 2021) in combination with deep mutational scanning studies to identify specificity regions in tail fibers (Huss et al, 2021) could help achieve this goal.…”

Section: Discussionmentioning

confidence: 99%

Genetic determinants of host tropism inKlebsiellaphages

Beamud

García-González

Gómez-Ortega

et al. 2022

Preprint

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Bacteriophages play key roles in bacterial ecology and evolution and are potential antimicrobials. However, the determinants of phage-host specificity remain elusive. Here, we used 46 newly-isolated phages to challenge 138 representative clinical isolates ofKlebsiella pneumoniae, a widespread opportunistic pathogen. Spot tests revealed a narrow host range for most phages, with <2% of 6319 phage-host combinations tested yielding detectable interactions. Bacterial capsule diversity was the main factor restricting phage host range. Consequently, phage-encoded depolymerases were key determinants of host tropism, and we identified depolymerase sequence types associated with the ability to infect specific capsular types across phage families. Phages showing a capsule-independent mode of entry exhibited a much broader host range, but their infectivity was still restricted by complex intracellular defense mechanisms. These findings expand our knowledge of the complex interactions between bacteria and their viruses, and have implications for the biomedical and biotechnological use of phages.

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Section: Discussionmentioning

confidence: 99%

Genetic determinants of host tropism inKlebsiellaphages

Beamud

García-González

Gómez-Ortega

et al. 2022

Preprint

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“…Conversely, whenever the patient's infection can be satisfactorily treated with antibiotics, those will always be the therapy of choice. Additionally, a proper diagnostic of the infection-causing bacteria must be conducted (see Section 5), as well as a susceptibility proof of such bacteria towards the phage preparation to be applied (what is known as a "phagogram") [100,101]. We provide details below on the most urgent indications in which a regularization of phage therapy could have a greater impact.…”

Section: Most Urgent Indications For the Application Of Phage Therapy...mentioning

confidence: 99%

Essential Topics for the Regulatory Consideration of Phages as Clinically Valuable Therapeutic Agents: A Perspective from Spain

Vázquez

Díez-Martínez²,

Domingo‐Calap

et al. 2022

Microorganisms

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Antibiotic resistance is one of the major challenges that humankind shall face in the short term. (Bacterio)phage therapy is a valuable therapeutic alternative to antibiotics and, although the concept is almost as old as the discovery of phages, its wide application was hindered in the West by the discovery and development of antibiotics in the mid-twentieth century. However, research on phage therapy is currently experiencing a renaissance due to the antimicrobial resistance problem. Some countries are already adopting new ad hoc regulations to favor the short-term implantation of phage therapy in clinical practice. In this regard, the Phage Therapy Work Group from FAGOMA (Spanish Network of Bacteriophages and Transducing Elements) recently contacted the Spanish Drugs and Medical Devices Agency (AEMPS) to promote the regulation of phage therapy in Spain. As a result, FAGOMA was asked to provide a general view on key issues regarding phage therapy legislation. This review comes as the culmination of the FAGOMA initiative and aims at appropriately informing the regulatory debate on phage therapy.

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“…The second layer covers the evolutionary dynamics between host and phage, e.g., genetic defense mechanisms such as CRISPR-Cas. The last layer incorporates metabolic conversion of the host by the virus, e.g., by using transcriptomics data ( Lood et al, 2022 ).…”

Section: Engineering Of Clostridioides Difficile A...mentioning

confidence: 99%

Battling Enteropathogenic Clostridia: Phage Therapy for Clostridioides difficile and Clostridium perfringens

2022

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The pathogenic Clostridioides difficile and Clostridium perfringens are responsible for many health care-associated infections as well as systemic and enteric diseases. Therefore, they represent a major health threat to both humans and animals. Concerns regarding increasing antibiotic resistance (related to C. difficile and C. perfringens) have caused a surge in the pursual of novel strategies that effectively combat pathogenic infections, including those caused by both pathogenic species. The ban on antibiotic growth promoters in the poultry industry has added to the urgency of finding novel antimicrobial therapeutics for C. perfringens. These efforts have resulted in various therapeutics, of which bacteriophages (in short, phages) show much promise, as evidenced by the Eliava Phage Therapy Center in Tbilisi, Georgia (https://eptc.ge/). Bacteriophages are a type of virus that infect bacteria. In this review, the (clinical) impact of clostridium infections in intestinal diseases is recapitulated, followed by an analysis of the current knowledge and applicability of bacteriophages and phage-derived endolysins in this disease indication. Limitations of phage and phage endolysin therapy were identified and require considerations. These include phage stability in the gastrointestinal tract, influence on gut microbiota structure/function, phage resistance development, limited host range for specific pathogenic strains, phage involvement in horizontal gene transfer, and—for phage endolysins—endolysin resistance, -safety, and -immunogenicity. Methods to optimize features of these therapeutic modalities, such as mutagenesis and fusion proteins, are also addressed. The future success of phage and endolysin therapies require reliable clinical trial data for phage(-derived) products. Meanwhile, additional research efforts are essential to expand the potential of exploiting phages and their endolysins for mitigating the severe diseases caused by C. difficile and C. perfringens.

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Digital phagograms: predicting phage infectivity through a multilayer machine learning approach

Cited by 32 publications

References 87 publications

Genetic determinants of host tropism inKlebsiellaphages

Genetic determinants of host tropism inKlebsiellaphages

Essential Topics for the Regulatory Consideration of Phages as Clinically Valuable Therapeutic Agents: A Perspective from Spain

Battling Enteropathogenic Clostridia: Phage Therapy for Clostridioides difficile and Clostridium perfringens

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