Loss of GdpP Function in Staphylococcus aureus Leads to β-Lactam Tolerance and Enhanced Evolution of β-Lactam Resistance
Raymond Poon, Li Basuino, Nidhi Satishkumar, Aditi Chatterjee, Nagaraja Mukkayyan, Emma Buggeln, Liusheng Huang, Vinod Nair, Maria A. Argudín, Sandip K. Datta, Henry F. Chambers, Som S. Chatterjee
Abstract
led to an enhanced ability of the bacteria to withstand a β-lactam challenge (2 to 3 log increase in bacterial CFU) by promoting tolerance without enhancing MICs of β-lactam antibiotics. Our results demonstrated that increased drug tolerance due to loss of GdpP function can provide a selective advantage in acquisition of high-level β-lactam resistance. Loss of GdpP function thus increases tolerance to β-lactams that can lead to its therapy failure and can permit β-lactam resistance to occur more readily.
Topics & Concepts
Staphylococcus aureusMicrobiologyLoss functionBacteriaBiologyDrug resistanceAntibioticsDrug toleranceAntibiotic resistanceStaphylococcal infectionsMultidrug toleranceFunction (biology)PhosphodiesteraseMutationEscherichia coliMicrococcaceaeStaphylococcusAntibacterial agentBacterial geneticsMethicillin-resistant Staphylococcus aureusDrugAntimicrobial Resistance in StaphylococcusAntibiotic Resistance in BacteriaAntimicrobial agents and applications