ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Antibiotic Resistance and New Antimicrobial drugs
Busulfan inhibits Pseudomonas aeruginosa growth and reduces biofilm biomass and pyocyanin production
Provisionally accepted
Needa A. Bahkali1
Rhodanne Nicole A. Lambarte2
Terrence S. Sumague2
Turki M. Dawoud1
Khalid S. Almaary1
Abdurahman A. Niazy3*- 1King Saud University College of Science, Riyadh, Saudi Arabia
- 2King Saud University Medical City Prince Naif bin Abdulaziz Health Research Center, Riyadh, Saudi Arabia
- 3King Saud University College of Dentistry, Riyadh, Saudi Arabia
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Pseudomonas aeruginosa remains a serious threat in clinical settings, especially in patients who are immunocompromised, receiving chemotherapy, or in intensive care units. With the rise of antibiotic resistance, drug repurposing offers a promising alternative strategy. Busulfan, an anticancer alkylating agent that induces DNA cross-linking and cytotoxic effects on cancer cells, may exert similar effects on microorganisms, as reported for other alkylating agents. This study evaluated the antibacterial potential of busulfan against P. aeruginosa. Initially, the antimicrobial activity of busulfan was assessed using the microdilution method, followed by investigations on key virulence factors of the PAO1 strain after treatment. Busulfan inhibited bacterial growth in a dose-dependent manner, with 84% inhibition observed at 108 µg/mL, while bactericidal activity was only observed at much higher concentrations (MBC >512 and <1024 µg/mL). Busulfan significantly reduced biofilm formation by 55%, live cell viability by 67% as observed via confocal laser scanning microscopy (CLSM), decreased pyocyanin production by 57%, and impaired iron-chelation ability by 25%. Moreover, moderate synergy with gentamicin was observed with higher concentration of busulfan. However, treatment with 108 µg/mL busulfan showed no effect on PAO1 hemolysis and motility. Busulfan demonstrates antimicrobial activity against P. aeruginosa, particularly through its effects on virulence factors. These preliminary results support the potential value of busulfan for repurposing, though further studies are needed to clarify its mechanism and therapeutic relevance.
Keywords: Busulfan, anticancer, drug repurposing, Pseudomonas aeruginosa, Virulencefactors, Antibacterial
Received: 09 Oct 2025; Accepted: 29 Nov 2025.
Copyright: © 2025 Bahkali, Lambarte, Sumague, Dawoud, Almaary and Niazy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Abdurahman A. Niazy
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