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

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.

Assessment of the effect of two different doses of intranasal nitroglycerine spray on attenuation of haemodynamic stress response to pneumoperitoneum in laparoscopic surgeries: A randomised, double-blinded study.

Background and Aims: The stress response to pneumoperitoneum can be deleterious due to its effects on haemodynamics, thereby increasing the morbidity. We intended to compare different doses of nitroglycerine nasal spray to obtund these responses and to look for any side effects. Methods: After ethical committee clearance and clinical trials registration, 70 patients scheduled for laparoscopic cholecystectomy were recruited. Random allocation was done into two groups by a computer generated randomisation table. Group N4 (n = 35) received 400 µg nitroglycerine and group N8 (n = 35) received 800 µg nitroglycerine with an intranasal spray 2 min prior to pneumoperitoneum. All the haemodynamic parameters were monitored at regular intervals. Results: The heart rate was comparable between the groups except at 6 and 10 min of pneumoperitoneum but showed significant increase from baseline within the groups. Mean arterial pressure (MAP) was statistically significant between the groups, being higher in group N4. Within group N4, MAP was significantly low only at 2 min, 4 min of pneumoperitoneum (101.69 ± 12.34 at baseline versus 93.31 ± 8.07 at 2 min and 97.54 ± 9.07 mm Hg at 4 min) and increased significantly at 30 min of pneumoperitoneum (101.69 ± 12.34 at baseline versus 105.66 ± 12.35 mm Hg) and hence, MAP was observed to be around baseline throughout the rest of intraoperative period. Within group N8, there was a significant decrease in mean, systolic and diastolic blood pressure from baseline at most of the time intervals. Conclusion: 800 µg of intranasal nitroglycerine effectively obtunds the hypertensive response associated with pneumoperitoneum as compared to 400 µg without significant side effects.