An optimized cyclophosphamide-treated mouse model of Mycobacterium abscessus pulmonary infection.

Mycobacterium abscessus pulmonary infections are increasingly problematic, especially for immunocompromised individuals and those with underlying lung conditions. Currently, there is no reliable standardized treatment, underscoring the need for improved preclinical drug testing. We present a simplified immunosuppressed mouse model using only four injections of cyclophosphamide, which allows for sustained M. abscessus lung burden for up to 16 days. This model proved effective for antibiotic efficacy evaluation, as demonstrated with imipenem or amikacin.

Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa.

Since its discovery 22 years ago, the bacterial cell-to-cell communication system, termed quorum sensing (QS), has shown potential as antipathogenic target. Previous studies reported that ajoene from garlic inhibits QS in opportunistic human pathogen Pseudomonas aeruginosa. In this study, screening of an in-house compound library revealed two sulfur-containing compounds which possess structural resemblance with ajoene and inhibit QS in bioreporter assay. Following a quantitative structure-activity relationship (SAR) study, 25 disulfide bond-containing analogues were synthesized and tested for QS inhibition activities. SAR study indicated that the allyl group could be replaced with other substituents, with the most active being benzothiazole derivative (IC50 = 0.56 µM). The compounds were able to reduce QS-regulated virulence factors (elastase, rhamnolipid, and pyocyanin) and successfully inhibit P. aeruginosa infection in murine model of implant-associated infection. Altogether, the QS inhibition activity of the synthesized compounds is encouraging for further exploration of novel analogues in antimicrobial drug development.

Detection of Pathogenic Biofilms with Bacterial Amyloid Targeting Fluorescent Probe, CDy11.

Bacterial biofilms are responsible for a wide range of persistent infections. In the clinic, diagnosis of biofilm-associated infections relies heavily on culturing methods, which fail to detect nonculturable bacteria. Identification of novel fluorescent probes for biofilm imaging will greatly facilitate diagnosis of pathogenic bacterial infection. Herein, we report a novel fluorescent probe, CDy11 (compound of designation yellow 11), which targets amyloid in the Pseudomonas aeruginosa biofilm matrix through a diversity oriented fluorescent library approach (DOFLA). CDy11 was further demonstrated for in vivo imaging of P. aeruginosa in implant and corneal infection mice models.