A novel antibiotic 3-isopropylhexahydro-4H-pyrido[1,2-α]pyrazine-1,4(6H)-dione isolated from the thermophilic bacterium Bacillus licheniformis QX928

Abstract

A microbial strain designated Bacillus licheniformis QX928 was screened from hot springs in Sichuan Province, China, and a compound generated in the culture of this strain clearly inhibited Pseudomonas aeruginosa ATCC27853. The measured minimum inhibitory and lowest bactericidal concentrations were (13±0.17) and (22±0.72) mg L-1, respectively. The compound was identified as 3-isopropylhexahydro-4H-pyrido[1,2-α]pyrazine-1,4(6H)-dione (IPHPPD). A SciFinder search revealed that IPHPPD could be the first compound synthesized by microorganisms that had both antibacterial and anti-quorum sensing properties. At low concentrations, IPHPPD interfered with the signaling factors and population effects of P. aeruginosa, thereby altering the biofilm morphology and structure. IPHPPD more strongly inhibited P. aeruginosa at high concentrations, primarily by reducing its virulence factors, cell membrane permeability and energy metabolism. A transcriptome analysis highlighted the role of IPHPPD in the transcriptional regulation of cellular metabolism and quorum sensing. Thus, the results of this study provide critical evidence that IPHPPD is a potential target for drug development to prevent and treat diseases in animals.