Effect of phenylalanine arginyl β-naphthylamide on the imipenem resistance, elastase production, and the expression of quorum sensing and virulence factor genes in Pseudomonas aeruginosa clinical isolates

• Published in: Brazilian journal of microbiology Vol. 55; no. 3; pp. 2715 - 2726
• Main Authors: Zolpirani, Fatemeh Hojjati, Ghaemi, Ezat Allah, Yasaghi, Mohammad, Nikokar, Iraj, Ardebili, Abdollah
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.09.2024; Springer Nature B.V
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biomedical and Life Sciences; Carbapenems; Clinical isolates; Diffusion pumps; Dipeptides - pharmacology; Drug resistance; Drug Resistance, Bacterial; Efflux; Elastase; Food Microbiology; Gene expression; Gene Expression Regulation, Bacterial - drug effects; Genes; Humans; Imipenem; Imipenem - pharmacology; Inhibitors; Life Sciences; Medical Microbiology; Medicine and Public Health - Research Paper; Metalloendopeptidases; Microbial Ecology; Microbial Genetics and Genomics; Microbial Sensitivity Tests; Microbiology; Multidrug resistance; Mycology; Nosocomial infection; Pancreatic Elastase - genetics; Pancreatic Elastase - metabolism; Pathogenesis; Phenylalanine; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - isolation & purification; Pseudomonas Infections - microbiology; Quorum sensing; Quorum Sensing - drug effects; Real time; Resistance factors; Respiratory tract; Respiratory tract infection; Virulence; Virulence factors; Virulence Factors - genetics; Virulence Factors - metabolism; Real-time quantitative reverse transcription PCR; Quorum sensing; Elastase B; Phenylalanine arginyl β-naphthylamide; Pseudomonas aeruginosa
• ISSN: 1517-8382; 1678-4405; 1678-4405
• DOI: 10.1007/s42770-024-01426-7

Pseudomonas aeruginosa is one of the most important nosocomial pathogens that possess the ability to produce multiple antibiotic resistance and virulence factors. Elastase B (LasB) is the major factor implicated in tissue invasion and damage during P. aeruginosa infections, whose synthesis is regulated by the quorum sensing (QS) system. Anti-virulence approach is now considered as potential therapeutic alternative and/or adjuvant to current antibiotics’ failure. The aim of this study is primarily to find out the impact of the efflux pump inhibitor (EPI) phenylalanine arginyl β-naphthylamide (PAβN) on the production of elastase B and the gene expression of lasI quorum sensing and lasB virulence factor in clinical isolates of P. aeruginosa . Five P. aeruginosa isolates recovered from patients with respiratory tract infections were examined in this study. Antimicrobial susceptibility of isolates was performed by the disk agar diffusion method. Effect of the PAβN on imipenem susceptibility, bacterial viability, and elastase production was evaluated. The expression of lasB and lasI genes was measured by quantitative real-time PCR in the presence of PAβN. All isolates were identified as multidrug-resistant (MDR) and showed resistance to carbapenem (MIC = 64–256 µg/mL). Susceptibility of isolates to imipenem was highly increased in the presence of efflux inhibitor. PAβN significantly reduced elastase activity in three isolates tested without affecting bacterial growth. In addition, the relative expression of both lasB and lasI genes was diminished in all isolates in the presence of inhibitor. Efflux inhibition by using the EPI PAβN could be a potential target for controlling the P. aeruginosa virulence and pathogenesis. Furthermore, impairment of drug efflux by PAβN indicates its capability to be used as antimicrobial adjuvant that can decrease the resistance and lower the effective doses of current drugs.