journal article·2024-11-05Open access

Antimicrobial, Synergistic, and Antibiofilm Activity of Sildenafil Against Pseudomonas aeruginosa: Preliminary Studies

Thais de Moraes Barin, Camilla Filippi dos Santos Alves, Cristiane Antunes Teixeira, Camila Marina Verdi, Kelly Schneider Moreira, Thiago Burgo, Vitória Fernanda Belmonte Novais, Rodrigo de Almeida Vaucher, Roberto Christ Vianna Santos

Applied Sciences· Volume 14· Issue 22

Abstract

The present study tested sildenafil citrate as an example of pharmacological repositioning against the opportunistic pathogen Pseudomonas aeruginosa, known for its potent biofilm formation. We evaluated its antimicrobial, synergistic, and antibiofilm effects using broth microdilution, checkerboard assays, and atomic force microscopy techniques. Sildenafil citrate showed antimicrobial activity, effectively inhibiting bacterial growth at minimum inhibitory concentrations ranging from 3.12 to 6.25 mg/mL and minimum bactericidal concentrations between 3.12 and 25 mg/mL. When combined with reference antimicrobial agents—cefepime, imipenem, cilastatin, and polymyxin—sildenafil citrate had a synergistic effect. It also effectively inhibited and eradicated biofilms, reducing total biomass by 87.1% for inhibition and 83.8% for eradication. Atomic force microscopy confirmed the efficacy of sildenafil citrate in destroying and inhibiting biofilms, decreasing the overall amplitude of the biofilm. Consequently, sildenafil citrate appears to be a promising candidate for combination with commercial antimicrobial drugs to prevent and treat P. aeruginosa infections.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Phenothiazines and Benzothiazines Synthesis and Activities · Bacterial biofilms and quorum sensing · Antimicrobial Peptides and Activities

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Industrial Pharmacy, Federal University of Santa Maria, Santa Maria 97105-900, Rio Grande do Sul, Brazil

Oral Microbiology Research Laboratory, Microbiology, and Parasitology Department, Federal University of Santa Maria, Santa Maria 97105-900, Rio Grande do Sul, Brazil

Chemistry Department, Universidade Estadual Paulista Júlio de Mesquita Filho, UNESP, Rio Claro 13506-900, São Paulo, Brazil

Laboratório de Pesquisa em Bioquímica e Biologia Molecular de Micro-Organismos, Federal University of Pelotas, Pelotas 96160-000, Rio Grande do Sul, Brazil

Funding

CNPq Brazil · CNPq · FAPERGS

References (23)

Show source-provided references
1. Review of Drug Repositioning Approaches and Resources10.7150/ijbs.24612 ↗
2. Chemical Sanitizers to Control Biofilms Formed by Two Pseudomonas Species on Stainless Steel Surface10.1590/S0101-20612012005000008 ↗
3. In Silico Repositioning of Approved Drugs for Rare and Neglected Diseases10.1016/j.drudis.2011.02.016 ↗
4. Clinical and Laboratory Standards Institute (CLSI) (2020, January 01). Standard for Quality in Your Laboratory with CLSI. Available online: www.clsi.org.
5. Maiga, M., Agarwal, N., Ammerman, N.C., Gupta, R., and Guo, H. (2012). Successful Shortening of Tuberculosis Treatment Using Adjuvant Host-Directed Therapy with FDA-Approved Phosphodiesterase Inhibitors in the Mouse Model. PLoS ONE, 7.10.1371/journal.pone.0030749 ↗
6. Long-Term Treatment with Sildenafil Citrate in Pulmonary Arterial Hypertension: The SUPER-2 Study10.1378/chest.10-0969 ↗
7. Sildenafil in endotoxin-induced pulmonary hypertension: An experimental study
8. Sildenafil for treating patients with COVID-19 and perfusion mismatch: A pilot randomized trial10.1186/s13054-021-03885-y ↗
9. Oliynyk, O.V., Rorat, M., Strepetova, O.V., Dubrov, S.O., Guryanov, V.G., Oliynyk, Y.V., Kulivets, O.S., Ślifirczyk, A., and Barg, W. (2023). Efficacy of Sildenafil in Patients with Severe COVID-19 and Pulmonary Arterial Hypertension. Viruses, 15.10.3390/v15051157 ↗
10. Drug Therapy for Unexplained Dyspnea in Post-COVID-19 Fatigue Syndrome: Empagliflozin and Sildenafil10.1097/MJT.0000000000001483 ↗
11. Use of sildenafil in patients with severe COVID-19 pneumonitis10.1016/j.bja.2022.04.004 ↗
12. Anti-infection mechanism of phosphodiesterase-5 inhibitors and their roles in coronavirus disease 201910.3892/etm.2021.9751 ↗
13. Matange, N. (2015). Revisiting bacterial cyclic nucleotide phosphodiesterases: Cyclic AMP hydrolysis and beyond. FEMS Microbiol. Lett., 362.10.1093/femsle/fnv183 ↗
14. Inhibition of P. aeruginosa c-di-GMP phosphodiesterase RocR and swarming motility by a benzoisothiazolinone derivative10.1039/C6SC02103D ↗
15. Sulfonamides Complexed with Metals as Mycobacterial Biofilms Inhibitors10.1016/j.jctube.2021.100217 ↗
16. Biofilm Infections, Their Resilience to Therapy and Innovative Treatment Strategies10.1111/joim.12004 ↗
17. Geometria Fractal: Propriedades e Características de Fractais Ideais
18. Prospective, Open-Label, Uncontrolled Pilot Study to Study Safety and Efficacy of Sildenafil in Systemic Sclerosis-Related Pulmonary Artery Hypertension and Cutaneous Vascular Complications10.1007/s00296-012-2466-5 ↗
19. Susceptibility of Monospecies and Dual-Species Biofilms of Staphylococcus Aureus and Escherichia Coli to Essential Oils10.1111/j.1745-4565.2012.00387.x ↗
20. Advances in the Design and Discovery of Drugs for the Treatment of Prostatic Hyperplasia
21. Pseudomonas Biofilm Matrix Composition and Niche Biology10.1111/j.1574-6976.2011.00322.x ↗
22. Cyclic Di-GMP: Second Messenger Extraordinaire10.1038/nrmicro.2016.190 ↗
23. Zych, M., Roszczyk, A., Kniotek, M., Kaleta, B., and Zagozdzon, R. (2019). Sildenafil Citrate Influences Production of TNF-α in Healthy Men Lymphocytes. J. Immunol. Res., 8478750.10.1155/2019/8478750 ↗