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Cited by 1Bacterial biofilms and quorum sensingAntibiotic Resistance in BacteriaStructural and Chemical Analysis of Organic and Inorganic Compounds

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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

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Rahimbakhsh, Ali, Seyfahmadi, Mahdi, Souldozi, Ali, Hakimelahi, Rakhshan, Alikhani, Mohammad Yousef, Kafilzadeh, Farshid·2025·Scientific Reports
DOI 10.1038/s41598-025-23260-zPMC PMC12606102
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Abstract

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.

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Fig. 1 Anti-biofilm activity of 1,3,4-oxadiazole against Acinetobacter baumannii isolates. Data are expressed as mean ± SD from three independent experiments (n = 3). A significant reduction in biofilm formation was observed in all treated isolates compared with the untreated control (p < 0.05).
Fig. 1 Anti-biofilm activity of 1,3,4-oxadiazole against Acinetobacter baumannii isolates. Data are expressed as mean ± SD from three independent experiments (n = 3). A significant reduction in biofilm formation was observed in all treated isolates compared with the untreated control (p < 0.05).CC BY-NC-ND · PubMed Central
Fig. 2 Downregulation of the biofilm-associated bap gene in Acinetobacter baumannii isolates exposed to sub-inhibitory concentrations of 1,3,4-oxadiazole. Expression levels are presented as log2-fold change relative to untreated controls. Data represent mean ± SD from three independent experiments (n = 3).
Fig. 2 Downregulation of the biofilm-associated bap gene in Acinetobacter baumannii isolates exposed to sub-inhibitory concentrations of 1,3,4-oxadiazole. Expression levels are presented as log2-fold change relative to untreated controls. Data represent mean ± SD from three independent experiments (n = 3).CC BY-NC-ND · PubMed Central
Fig. 3 Effect of 1,3,4-Oxadiazole on Acinetobacter baumannii Biofilms (A) Untreated A. baumannii biofilm exhibiting substantial large biofilm biomass (LBB). (B and C) A. baumannii biofilm treated with 15.62 μg/mL of 1,3,4-oxadiazole, showing a significant reduction in biofilm biomass (small biofilm biomass, SBB).
Fig. 3 Effect of 1,3,4-Oxadiazole on Acinetobacter baumannii Biofilms (A) Untreated A. baumannii biofilm exhibiting substantial large biofilm biomass (LBB). (B and C) A. baumannii biofilm treated with 15.62 μg/mL of 1,3,4-oxadiazole, showing a significant reduction in biofilm biomass (small biofilm biomass, SBB).CC BY-NC-ND · PubMed Central

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Metadata

Authors
Rahimbakhsh, A., Seyfahmadi, M., Souldozi, A., Hakimelahi, R., Alikhani, M. Y., & Kafilzadeh, F.
Affiliations
  • Islamic Azad University, Jahrom Branch (IR)
  • Islamic Azad University of Urmia (IR)
  • Hamedan University of Medical Sciences (IR)
Corresponding author
  • Alikhani, Mohammad Yousef
  • Kafilzadeh, Farshid
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2025-11-11
Volume
15
Issue
1
Pages
39543-39543
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-025-23260-z
PMC
PMC12606102
OpenAlex
W4416114295
Cited by
1
References
31
Citations by year
2026: 1
FWCI
0.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
  • Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
  • Physical Sciences › Chemistry › Organic Chemistry › Structural and Chemical Analysis of Organic and Inorganic Compounds
Keywords
Acinetobacter baumannii, multidrug resistance, biofilm formation, bap gene, biofilm genes, antibiofilm activity, antibacterial activity, minimum inhibitory concentration, minimum bactericidal concentration, cytotoxicity, clinical isolates, gentamicin resistance
MeSH terms
Acinetobacter Infections, Anti-Bacterial Agents, Bacterial Proteins, Humans, Microbial Sensitivity Tests, Oxadiazoles, Gene Expression Regulation, Bacterial, Biofilms, Drug Resistance, Multiple, Bacterial, Acinetobacter baumannii

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CoChat. (2026). Citation check: Effect of 1,3,4-oxadiazoles on expression of biofilm-associated bap gene in clinical isolates of multidrug-resistant Acinetobacter baumannii. https://app.cochat.ai/papers/10.1038/s41598-025-23260-z
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Rahimbakhsh, A., Seyfahmadi, M., Souldozi, A., Hakimelahi, R., Alikhani, M. Y., & Kafilzadeh, F. (2025). Effect of 1,3,4-oxadiazoles on expression of biofilm-associated bap gene in clinical isolates of multidrug-resistant Acinetobacter baumannii. Scientific Reports. https://doi.org/10.1038/s41598-025-23260-z