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<p>The rise of multidrug-resistant (MDR) pathogens, particularly <i>Acinetobacter baumannii</i>, poses a significant threat to global health due to its resistance to multiple antibiotics, biofilm-forming capacity, and associated poor clinical outcomes. This study aimed to evaluate the antibacterial and antibiofilm efficacy of 1,3,4-oxadiazole against <i>A. baumannii</i>, focusing on biofilm-related challenges and gene expression. A one-step, high-yield method was used to synthesize the 1,3,4-oxadiazoles. Thirteen <i>A. baumannii</i> isolates were collected from clinical samples and assessed for biofilm formation using microtiter plate assays. Antimicrobial susceptibility was determined via the Kirby-Bauer disk diffusion method, while the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 1,3,4-oxadiazole were evaluated following CLSI guidelines. PCR was used to detect the presence of biofilm-associated (<i>bap</i>) gene. The inhibitory effect of 1,3,4-oxadiazole on biofilm formation and <i>bap</i> gene expression (using RT-qPCR) was assessed, alongside cytotoxicity testing on the A549 lung cancer cell line. Among eight selected clinical isolates, 100% were MDR, exhibiting high resistance to gentamicin, ciprofloxacin, and imipenem. Biofilm assays classified the isolates as strong, moderate, or weak producers, with the presence of the <i>bap</i> gene significantly associated with biofilm formation (<i>p</i> &lt; 0.05). MIC and MBC values of 1,3,4-oxadiazole ranged from 7.81–31.25 µg/ml and 7.81–62.5 µg/ml, respectively. Sub-MIC concentrations significantly inhibited biofilm formation (43–79% reduction) and downregulated <i>bap</i> expression (log2-fold change: 0.24–4.13). Cytotoxicity analysis confirmed no significant effects on A549 cells at 15.62 and 7.81 µg (<i>p</i> = 0.085). 1,3,4-Oxadiazole exhibits significant antibacterial and antibiofilm properties against MDR <i>A. baumannii</i>, effectively targeting biofilm-associated genes and demonstrating a favorable safety profile. These findings highlight the potential of 1,3,4-oxadiazole as a promising candidate for combating MDR infections and biofilm-related complications.</p>

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Effect of 1,3,4-oxadiazoles on expression of biofilm-associated bap gene in clinical isolates of multidrug-resistant Acinetobacter baumannii

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月11日

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  • Ali Rahimbakhsh,
  • Mahdi Seyfahmadi,
  • Ali Souldozi,
  • Rakhshan Hakimelahi,
  • Mohammad Yousef Alikhani,
  • Farshid Kafilzadeh

摘要

The rise of multidrug-resistant (MDR) pathogens, particularly Acinetobacter baumannii, poses a significant threat to global health due to its resistance to multiple antibiotics, biofilm-forming capacity, and associated poor clinical outcomes. This study aimed to evaluate the antibacterial and antibiofilm efficacy of 1,3,4-oxadiazole against A. baumannii, focusing on biofilm-related challenges and gene expression. A one-step, high-yield method was used to synthesize the 1,3,4-oxadiazoles. Thirteen A. baumannii isolates were collected from clinical samples and assessed for biofilm formation using microtiter plate assays. Antimicrobial susceptibility was determined via the Kirby-Bauer disk diffusion method, while the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 1,3,4-oxadiazole were evaluated following CLSI guidelines. PCR was used to detect the presence of biofilm-associated (bap) gene. The inhibitory effect of 1,3,4-oxadiazole on biofilm formation and bap gene expression (using RT-qPCR) was assessed, alongside cytotoxicity testing on the A549 lung cancer cell line. Among eight selected clinical isolates, 100% were MDR, exhibiting high resistance to gentamicin, ciprofloxacin, and imipenem. Biofilm assays classified the isolates as strong, moderate, or weak producers, with the presence of the bap gene significantly associated with biofilm formation (p < 0.05). MIC and MBC values of 1,3,4-oxadiazole ranged from 7.81–31.25 µg/ml and 7.81–62.5 µg/ml, respectively. Sub-MIC concentrations significantly inhibited biofilm formation (43–79% reduction) and downregulated bap expression (log2-fold change: 0.24–4.13). Cytotoxicity analysis confirmed no significant effects on A549 cells at 15.62 and 7.81 µg (p = 0.085). 1,3,4-Oxadiazole exhibits significant antibacterial and antibiofilm properties against MDR A. baumannii, effectively targeting biofilm-associated genes and demonstrating a favorable safety profile. These findings highlight the potential of 1,3,4-oxadiazole as a promising candidate for combating MDR infections and biofilm-related complications.