New Auranofin Analogs with Antibacterial Properties against <i>Burkholderia</i> Clinical Isolates

• Main Authors: Dustin Maydaniuk (Author), Bin Wu (Author), Dang Truong (Author), Sajani H. Liyanage (Author), Andrew M. Hogan (Author), Zhong Ling Yap (Author), Mingdi Yan (Author), Silvia T. Cardona (Author)
• Format: Book
• Published: MDPI AG, 2021-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics10121443; 2079-6382
• Keywords: <i>Burkholderia</i>; <i>Burkholderia cepacia</i> complex; auranofin; antimicrobials; antibiotic resistance; cystic fibrosis; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 10, Iss 12, p 1443 (2021)

Bacteria of the genus <i>Burkholderia</i> include pathogenic <i>Burkholderia mallei</i>, <i>Burkholderia pseudomallei</i> and the <i>Burkholderia cepacia</i> complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment of infections difficult. Bcc affects individuals with cystic fibrosis (CF) and the species <i>B. cenocepacia</i> is associated with one of the worst clinical outcomes. Following the repurposing of auranofin as an antibacterial against Gram-positive bacteria, we previously synthetized auranofin analogs with activity against Gram-negatives. In this work, we show that two auranofin analogs, MS-40S and MS-40, have antibiotic activity against <i>Burkholderia</i> clinical isolates. The compounds are bactericidal against <i>B. cenocepacia</i> and kill stationary-phase cells and persisters without selecting for multistep resistance. <i>Caenorhabditis elegans</i> and <i>Galleria mellonella</i> tolerated high concentrations of MS-40S and MS-40, demonstrating that these compounds have low toxicity in these model organisms. In summary, we show that MS-40 and MS-40S have antimicrobial properties that warrant further investigations to determine their therapeutic potential against <i>Burkholderia</i> infections.