Characterizing the Mechanism of Inhibition Displayed by Imidocarb Dipropionate on Yersinia pestis
Abstract
With the growing antibiotic resistance crisis, there is a need for development of new antibiotics. Several antibiotic resistant, gram-negative bacteria employ a type III secretion system (T3SS) making it an attractive target for new drugs. The T3SS is a multi-protein complex organized in a needle-like structure used to inject host cells with effector proteins to cause infection. Imidocarb dipropionate is a known inhibitor of the T3SS of Yersinia pestis, the causative agent of the bubonic plague, however its mechanism of inhibition is unclear. The purpose of this research was to determine which protein of the T3SS of Y. pestis is being targeted by dipropionate. Various Y. pestis strains, each with different mutations in the T3SS, were evaluated, including ΔyopNx, mini-pCD1, and YscF D46A. The effect of dipropionate on each mutant strain was tested using a disk diffusion assay on Magnesium Oxalate Agar, where Y. pestis T3SS inhibition is seen as growth around a dipropionate disk when incubated at 37°C for 48h. Dipropionate inhibited secretion in all three mutant strains, suggesting that dipropionate does not require effector Yop proteins or chaperones to inhibit T3S. In vitro, T3S can be inhibited by calcium. Interestingly, dipropionate was still able to inhibit mutant strains that can secrete in the presence of calcium, suggesting that it uses a different mechanism than calcium to inhibit secretion. Future studies will continue to evaluate whether a component of the T3SS apparatus of Y. pestis is impacted by the inhibitory component of dipropionate or whether gene expression is affected.
Faculty Sponsors
Dr. Julie Torruellas Garcia
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-6-2021 12:00 PM
End Date
4-9-2021 12:00 PM
Characterizing the Mechanism of Inhibition Displayed by Imidocarb Dipropionate on Yersinia pestis
Alvin Sherman Library
With the growing antibiotic resistance crisis, there is a need for development of new antibiotics. Several antibiotic resistant, gram-negative bacteria employ a type III secretion system (T3SS) making it an attractive target for new drugs. The T3SS is a multi-protein complex organized in a needle-like structure used to inject host cells with effector proteins to cause infection. Imidocarb dipropionate is a known inhibitor of the T3SS of Yersinia pestis, the causative agent of the bubonic plague, however its mechanism of inhibition is unclear. The purpose of this research was to determine which protein of the T3SS of Y. pestis is being targeted by dipropionate. Various Y. pestis strains, each with different mutations in the T3SS, were evaluated, including ΔyopNx, mini-pCD1, and YscF D46A. The effect of dipropionate on each mutant strain was tested using a disk diffusion assay on Magnesium Oxalate Agar, where Y. pestis T3SS inhibition is seen as growth around a dipropionate disk when incubated at 37°C for 48h. Dipropionate inhibited secretion in all three mutant strains, suggesting that dipropionate does not require effector Yop proteins or chaperones to inhibit T3S. In vitro, T3S can be inhibited by calcium. Interestingly, dipropionate was still able to inhibit mutant strains that can secrete in the presence of calcium, suggesting that it uses a different mechanism than calcium to inhibit secretion. Future studies will continue to evaluate whether a component of the T3SS apparatus of Y. pestis is impacted by the inhibitory component of dipropionate or whether gene expression is affected.
