inp-0341 and Pseudomonas-Infections

is an opportunistic pathogen and a major cause of corneal infections worldwide. The bacterium secretes several toxins through its type III secretion system (T3SS) to subvert host immune responses. In addition, it is armed with intrinsic as well as acquired antibiotic resistance mechanisms that make treatment a significant challenge and new therapeutic interventions are needed. Type III secretion inhibitors have been studied as an alternative or in accompaniment to traditional antibiotics to inhibit virulence of bacteria. In this study, INP0341, a T3SS inhibitor, inhibited cytotoxicity by

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Cell Line; Cornea; Disease Models, Animal; Epithelial Cells; Humans; Hydrazines; Keratitis; Mice; Mice, Inbred C57BL; Pseudomonas aeruginosa; Pseudomonas Infections; Type III Secretion Systems; Virulence

Pseudomonas aeruginosa is an opportunistic pathogen that can be very hard to treat because of high resistance to different antibiotics and alternative treatment regimens are greatly needed. An alternative or a complement to traditional antibiotic is to inhibit virulence of the bacteria. The salicylidene acylhydrazide, INP0341, belongs to a class of compounds that has previously been shown to inhibit virulence in a number of Gram-negative bacteria. In this study, the virulence blocking effect of INP0341 on P. aeruginosa was studied in vitro and in vivo. Two important and closely related virulence system were examined, the type III secretion system (T3SS) that translocates virulence effectors into the cytosol of the host cell to evade immune defense and facilitate colonization and the flagella system, needed for motility and biofilm formation. INP0341 was shown to inhibit expression and secretion of the T3SS toxin exoenzyme S (ExoS) and to prevent bacterial motility on agar plates and biofilm formation. In addition, INP0341 showed an increased survival of P. aeruginosa-infected mice. In conclusion, INP0341 attenuates P. aeruginosa virulence.

Topics: Administration, Cutaneous; ADP Ribose Transferases; Animals; Anti-Bacterial Agents; Bacterial Physiological Phenomena; Bacterial Proteins; Bacterial Toxins; Biofilms; Burns; Drug Resistance, Multiple, Bacterial; Flagella; HeLa Cells; Humans; Hydrazines; Male; Mice, Inbred BALB C; Mutation; Pseudomonas aeruginosa; Pseudomonas Infections; Sigma Factor; Survival Analysis; Trans-Activators; Virulence; Wound Infection