CASE STUDY — Drug Discovery
Overcoming drug resistant bacteria.
Overview
Drug resistant bacteria are a rising threat to global health. More than 1.2 million people died from antimicrobial resistance in 2019 alone, with many of those deaths directly caused by six highly virulent pathogens (ESKAPE), including methicillin-resistant Staphylococcus aureus, or MRSA.
Challenge
Endolysins are a promising alternative to antibiotics to combat drug resistant bacteria. These phage enzymes are used by viruses to break open bacterial walls from the inside and spread infection, but they can also be leveraged to lyse those same bacterial walls from the outside. Because phages only infect one bacterial species, we need to identify endolysin sequences specific to the target bacteria.
Approach
Sequence to strain
Our bit-GEM database contains sequences from a wide variety of bacteria, many of which contain integrated phage genomes. Because the database is built on bit-MAP technology, whole genome reconstructions can be compared down to the sub-strain level, lending key specificity to identifying the right endolysin for the right bacterial target. With DNA tagged to a specific isolate, and because of the 1:1 relationship between sequences and strain, we can then mine bacterial species for the corresponding endolysin gene.
Result
- Endolysin identified by the bit-QED platform showed higher bactericidal activity than competitor endolysin, even with lower endolysin concentrations
- Diverse endolysins against gram positive as well as gram negative bacteria
- Showed combinatorial effects with common antibiotics, especially with Linezolid
- Efficiently disrupted bacterial biofilms, and killed bacteria in the biofilm
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