Capturing Antibiotic-Resistant Ribosomes
Technical Report,15 Jun 2018,14 Jun 2019
Saint Louis University Saint Louis United States
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The universally conserved nucleotide A2058 of 23S rRNA in all bacterial ribosomes, when methylated m6A2058,causes cross-resistance to multiple families of therapeutically important antibiotics. The abundance and essentiality of ribosomes make them an attractive target for the detection of resistant pathogens based on the unique m6A2058 signature. The goal of this study is to develop immunoreagents that can be used as a rapid diagnostic tool for antibiotic resistant bacteria. They can also be used as a capturing tool to isolate homogenous populations of m6A2058-ribosomes for structural and biochemical determination, a critical step to delineate the molecular mechanisms of new ribosome-targeting antibiotics. In Year1, our success in the initial phase Aims 1-2 has offered a solid proof-of-principle to further improve the immunoreagents that specifically recognize the resistant ribosomes bearing the m6A2058 modification. In addition to our effort in increasing the specificity, affinity and yield of the available immunoreagents, we will perform an in vitro phage display screen to identify synthetic peptides against the m6A2058 ribosome as proposed in Aim 3.
- Medicine and Medical Research