Antibiotic resistance is becoming a greater threat to combating bacterial infections. Pathways directly responsible for infection, such as those involved in virulence or immune evasion, are likely to be good targets for novel approaches to treating infection; however, these approaches are currently not being pursued due to the lack of understanding of the requirements for bacterial survival within the host. Pseudomonas aeruginosa (PsA) is one of the most virulent opportunistic human pathogens and is often highly resistant to antibiotic therapy. Although it is traditionally considered an extracellular pathogen, PsA has been shown to invade and survive inside host cells. We hypothesize that this ability to survive intracellularly allows bacteria to become antibiotic insensitive, leading to the formation of reservoirs for recurrent infections. We have developed an in vitro infection model where we have identified genes required for intracellular survival in epithelial cells. We have also found strain specificity among clinical isolates in the kinetics of survival and in their ability to become antibiotic insensitive, suggesting a genetic basis for these differences. We are screening a PsA mutant library to find factors involved in intracellular survival that could be the basis for the development of novel anti-infectives.
- Copyright © 2013 by The American Association of Immunologists, Inc.