Virtual Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2022

Lysins as promising therapeutics against Uropathogenic Escherichia coli (#201)

Syed Ahmed 1 , Urmi Bajpai 2 , Sarmad Hanif 1 , Bhakti Chavan 1 , Ritam Das 1 , Sanket Shah 1
  1. Techinvention Lifecare Pvt. Ltd, Mumbai, MAHARASHTRA, India
  2. Department of Biomedical Sciences, Acharya Narendra Dev College, Delhi, India

Background

Uropathogenic Escherichia coli (UPEC) is a predominant pathogen responsible for 80-90% of community-acquired and 30-50% of nosocomially-acquired urinary tract infections (UTIs). Although treatable, the rampant use of antibiotics has led to the emergence of multi-drug resistant (MDR) strains which can lead to complications, treatment failure, and increase in mortality and morbidity. The World Health Organization has described antibiotic resistance in uropathogens as a key pressure point in the growing global antimicrobial resistance (AMR) crisis.  Given the prevalence of MDR strains, we are exploring prophage-encoded lysins as a potential alternative to antibiotics. Lysins have an array of interesting features, making them as putative tools for the treatment  of UTIs.

Objective

Our study involved the identification and in silico characterization of distinguished lysin sequences targeting peptidoglycan (PG) in E. coli cell wall.

Methods

Distinguished lysin sequences were searched by BLAST homology search and by screening E. coli prophages in the database (using PHASTER). The identified lysin sequences were computationally characterized and their domain architecture (using NCBI-CDD, InterProScan) and physicochemical properties (using ProtParam) were examined. 

Results 

Globular and modular lysin sequences identified had predominantly lysozyme like domain (56%), gluocosaminidase and PG-binding domain composing of three alpha-helices. The in silico physiochemical analysis predicted eight enzymes to be secretory and also the presence of both positively charged and hydrophobic residues at the C-terminal end and cationic residues in the catalytic domain (known to contribute to the intrinsic bactericidal potential of lysins) was observed. Purification of these lysins as recombinant proteins and optimization of antibacterial assays in the presence of suitable outer membrane permeabilizers is underway.

Conclusion 

We believe investigating this bank of distinguished lysins will expand the existing repertoire of lysins against E. coli which could potentially lead to the development of potent ‘enzybiotics’. Furthermore, these enzybiotics can also serve as effective therapeutic agents in combating AMR as well as augmenting One Health and Sustainable Development Goals (SDGs) globally.

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