Genome analysis of triple phages that curtails MDR E. coli with ML based host receptor prediction and its evaluation.

Autor: Unnikrishnan VK; Center for Research On Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India.; Antimicrobial Resistance Lab, ASK-I-312, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India., Sundaramoorthy NS; Center for Research On Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India.; Translational Health Sciences Technology Institute, Faridabad, India., Nair VG; Center for Research On Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India.; Antimicrobial Resistance Lab, ASK-I-312, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India., Ramaiah KB; Center for Research On Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India.; Antimicrobial Resistance Lab, ASK-I-312, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India., Roy JS; Center for Research On Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India., Rajendran M; Center for Research On Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India., Srinath S; Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India., Kumar S; Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India., S PS; Center for Research On Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India., S SM; Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India. sumamohan@scbt.sastra.edu., Nagarajan S; Center for Research On Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India. sai@scbt.sastra.edu.; Antimicrobial Resistance Lab, ASK-I-312, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India. sai@scbt.sastra.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Dec 27; Vol. 13 (1), pp. 23040. Date of Electronic Publication: 2023 Dec 27.
DOI: 10.1038/s41598-023-49880-x
Abstrakt: Infections by multidrug resistant bacteria (MDR) are becoming increasingly difficult to treat and alternative approaches like phage therapy, which is unhindered by drug resistance, are urgently needed to tackle MDR bacterial infections. During phage therapy phage cocktails targeting different receptors are likely to be more effective than monophages. In the present study, phages targeting carbapenem resistant clinical isolate of E. coli U1007 was isolated from Ganges River (U1G), Cooum River (CR) and Hospital waste water (M). Capsid architecture discerned using TEM identified the phage families as Podoviridae for U1G, Myoviridae for CR and Siphoviridae for M phage. Genome sequencing showed the phage genomes varied in size U1G (73,275 bp) CR (45,236 bp) and M (45,294 bp). All three genomes lacked genes encoding tRNA sequence, antibiotic resistant or virulent genes. A machine learning (ML) based multi-class classification model using Random Forest, Logistic Regression, and Decision Tree were employed to predict the host receptor targeted by receptor binding protein of all 3 phages and the best performing algorithm Random Forest predicted LPS O antigen, LamB or OmpC for U1G; FhuA, OmpC for CR phage; and FhuA, LamB, TonB or OmpF for the M phage. OmpC was validated as receptor for U1G by physiological experiments. In vivo intramuscular infection study in zebrafish showed that cocktail of dual phages (U1G + M) along with colsitin resulted in a significant 3.5 log decline in cell counts. Our study highlights the potential of ML tool to predict host receptor and proves the utility of phage cocktail to restrict E. coli U1007 in vivo.
(© 2023. The Author(s).)
Databáze: MEDLINE
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