<i>pruR</i> and PA0065 Genes Are Responsible for Decreasing Antibiotic Tolerance by Autoinducer Analog-1 (AIA-1) in <i>Pseudomonas aeruginosa</i>

• Main Authors: Muhammad Reza Pahlevi (Author), Keiji Murakami (Author), Yuka Hiroshima (Author), Akikazu Murakami (Author), Hideki Fujii (Author)
• Format: Book
• Published: MDPI AG, 2022-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics11060773; 2079-6382
• Keywords: antibiotic tolerance; <i>Pseudomonas aeruginosa</i>; autoinducer analog-1; <i>pruR</i>; PA0066-65-64; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 11, Iss 6, p 773 (2022)

<i>Pseudomonas aeruginosa</i> infection is considered a high-risk nosocomial infection and is very difficult to eradicate because of its tolerance to antibiotic treatment. A new compound, autoinducer analog-1 (AIA-1), has been demonstrated to reduce antibiotic tolerance, but its mechanisms remain unknown. This study aimed to investigate the mechanisms of AIA-1 in the antibiotic tolerance of <i>P. aeruginosa</i>. A transposon mutant library was constructed using miniTn5pro, and screening was performed to isolate high tolerant mutants upon exposure to biapenem and AIA-1. We constructed a deletion mutant and complementation strain of the genes detected in transposon insertion site determination, <i>pruR</i> and PA0066-65-64, and performed killing assays with antibiotics and AIA-1. Gene expression upon exposure to biapenem and AIA-1 and their relationship to stress response genes were analyzed. High antibiotic tolerance was observed in Tn5-<i>pruR</i> and Tn5-PA0065 transposon mutants and their deletion mutants, Δ<i>pruR</i> and ΔPA0066-65-64. Complemented strains of <i>pruR</i> and PA0066-65-64 with their respective deletion mutants exhibited suppressed antibiotic tolerance. It was determined that deletion of PA0066-65-64 increased <i>rpoS</i> expression, and PA0066-65-64 affects antibiotic tolerance via the <i>rpoS</i> pathway. Additionally, antibiotics and AIA-1 were found to inhibit <i>pruR</i> and PA0066-65-64. This study proposed that <i>pruR</i> and PA0066-65-64 are members of the antibiotic tolerance suppressors.