Rapid identification of antibiotic-resistant bacteria will play a key role in solving the global antibiotic crisis by providing a route to targeted antibiotic administration. However, current bacterial infection diagnoses take up to 3 days which can lead to antibiotic treatment that is less effective. Here we report a microfluidic system with a ladder shaped design allowing us to generate a twofold serial dilution of antibiotics comparable to current national and international standards. Our consolidated design, with minimal handling steps cuts down the testing time for antibiotic susceptibility from 16–20 h to 4–5 h. Our feasibility testing results are consistent with the commercial antibiotic susceptibility testing (AST) results, showing a 91.75% rate of agreement for Gram-negative and Gram-positive bacterial isolated from canine urinary tract infections (UTI) and may be used without prior isolation or enrichment. This platform provides an adaptable and efficient diagnostic tool for antibiotic susceptibility testing.
- Award ID(s):
- 1854934
- PAR ID:
- 10352282
- Author(s) / Creator(s):
- ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »
- Date Published:
- Journal Name:
- Clinical infectious diseases
- Volume:
- 73
- ISSN:
- 1058-4838
- Page Range / eLocation ID:
- e39
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Antimicrobial drug resistance demands novel approaches for improving the efficacy of antibiotics, especially against Gram‐negative bacteria. Herein, we report that conjugating a diglycine (GG) to an antibiotic prodrug drastically accelerates intrabacterial ester‐bond hydrolysis required for activating the antibiotic. Specifically, the attachment of GG to chloramphenicol succinate (CLsu) generates CLsuGG, which exhibits about an order of magnitude higher inhibitory efficacy than CLsu against
Escherichia coli . Further studies reveal that CLsuGG undergoes rapid hydrolysis, catalyzed by intrabacterial esterases (e.g., BioH and YjfP), to generate chloramphenicol (CL) inE. coli . Importantly, the conjugate exhibits lower cytotoxicity to bone marrow stromal cells than CL. Structural analogues of CLsuGG indicate that the conjugation of GG to an antibiotic prodrug is an effective strategy for accelerating enzymatic prodrug hydrolysis and enhancing the antibacterial efficacy of antibiotics. -
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