Fraunhofer USA CMI addresses the president's national action plan to combat antimicrobial resistance
The rise of bacterial resistance intensifies the need for rapid phenotype-based antibiotic susceptibility tests (ASTs) in order to safeguard our drugs of last resort. Standard ASTs are based on bacterial growth inhibition in the presence of antibiotics that take multiple (8-24) hours to complete. Fraunhofer CMI's biomedical researchers have developed a novel AST on a microfluidic platform that relies on the stress-activation of biosynthetic pathways to accelerate the action of antibiotics.
Fluid is passed at high speeds over bacteria immobilized on the bottom of a microfluidic channel. In the presence of stress and antibiotic, susceptible strains of bacteria die rapidly. However, resistant bacteria survive these stressful conditions. As compared to standard AST methods, the rate-limiting step - bacterial growth - is omitted during antibiotic application. The technical implementation of the method relies on several innovative techniques, including the use of culture media flow for mechanical stress application, the use of enzymes to damage but not kill the bacteria, and the use of microarray substrates for bacterial attachment.
This novel AST platform can successfully distinguish susceptible and resistant strains in less than an hour. Feasibility has been proven by testing a panel of Staphylococcus aureus strains against oxacillin. However, antibiotics with targets other than the cell wall have also been shown to work in our platform on this timeframe. Experiments with other Gram-positive and Gram-negative strains have been promising, and will be published in due course.
"This technique will pave the way for researchers to explore how bacteria respond to stress, and will impact the development of novel rapid diagnostics and the discovery of new drugs" says Dr. Alexis Sauer-Budge, Senior Researcher at Fraunhofer CMI.
The microfluidic AST platform is presented in the Journal of Visualized Experiments (JoVE):
Kalashnikov M, Campbell J, Lee JC, Sharon A, Sauer-Budge AF. Stress-induced Antibiotic Susceptibility Testing on a Chip. J Vis Exp. 2014(83). PubMed PMID: 24430495.