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Addressing Antibiotic Resistance: New Strategies for Overcoming the ESKAPE Pathogens

Periodic Reporting for period 2 - NO-ESKAPE (Addressing Antibiotic Resistance: New Strategies for Overcoming the ESKAPE Pathogens)

Reporting period: 2018-07-01 to 2019-12-31

Without effective antibiotics, many routine medical procedures carry a high risk and simple bacterial infections can become deadly. As more and more bacteria become resistant to antibiotics, doctors have fewer and fewer options for treating infections. This project outlines new chemistry-based strategies for developing novel antibiotics to address the threat of antibiotic resistance.
The research team working on the NO-ESKAPE project have made great progress towards the goals described above. In just the second year of the project we filed two patents that describe novel antibiotics that demonstrate very potent biological activity as well as new compounds that can block the resistance mechanisms that certain bacteria used to evade antibiotics.
The new lipopeptide antibiotics developed in the NO-ESAKPE project have been evaluated using in vitro assays and display activity that is significantly more potent than the recently approved clinically used lipopeptides that are considered to be state of the art (i.e. daptomycin). In addition, the small molecule inhibitors that we have developed to block the effect of the metallo-beta-lactamase (MBLs) enzymes represent the state of the art. At present there are no clinically used drugs that inhibit MBLs highlighting a serious unmet medical need that we aim to address in the NO-ESKAPE project. In the second half of the project the team will investigate the therapeutic potential of these new lipopeptide antibiotics and MBL inhibitors as a means of treating dangerous antibiotic-resistant infections.
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