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Combined Treatment of 6-Gingerol Analog and Tobramycin for Inhibiting Pseudomonas aeruginosa Infections
- Source :
- Microbiology Spectrum, Vol 9, Iss 2 (2021), Microbiology Spectrum
- Publication Year :
- 2021
- Publisher :
- American Society for Microbiology, 2021.
-
Abstract
- Pseudomonas aeruginosa is a ubiquitous human pathogen that causes severe infections. Although antibiotics, such as tobramycin, are currently used for infection therapy, their antibacterial activity has resulted in the emergence of multiple antibiotic-resistant bacteria. The 6-gingerol analog, a structural derivative of the main component of ginger, is a quorum sensing (QS) inhibitor. However, it has a lower biofilm inhibitory activity than antibiotics and the possibility to cause toxicity in humans. Therefore, novel and more effective approaches for decreasing dosing concentration and increasing biofilm inhibitory activity are required to alleviate P. aeruginosa infections. In this study, a 6-gingerol analog was combined with tobramycin to treat P. aeruginosa infections. The combined treatment of 6-gingerol analog and tobramycin showed strong inhibitory activities on biofilm formation and the production of QS-related virulence factors of P. aeruginosa compared to single treatments. Furthermore, the combined treatment alleviated the infectivity of P. aeruginosa in an insect model using Tenebrio molitor larvae without inducing any cytotoxic effects in human lung epithelial cells. The 6-gingerol analog showed these inhibitory activities at much lower concentrations when used in combination with tobramycin. Adjuvant effects were observed through increased QS-disrupting processes rather than through antibacterial action. In particular, improved RhlR inactivation by this combination is a possible target for therapeutic development in LasR-independent chronic infections. Therefore, the combined treatment of 6-gingerol analog and tobramycin may be considered an effective method for treating P. aeruginosa infections. IMPORTANCE Pseudomonas aeruginosa is a pathogen that causes various infectious diseases through quorum-sensing regulation. Although antibiotics are mainly used to treat P. aeruginosa infections, they cause the emergence of resistant bacteria in humans. To compensate for the disadvantages of antibiotics and increase their effectiveness, natural products were used in combination with antibiotics in this study. We discovered that combined treatment with 6-gingerol analog from naturally-derived ginger substances and tobramycin resulted in more effective reductions of biofilm formation and virulence factor production in P. aeruginosa than single treatments. Our findings support the notion that when 6-gingerol analog is combined with tobramycin, the effects of the analog can be exerted at much lower concentrations. Furthermore, its improved LasR-independent RhlR inactivation may serve as a key target for therapeutic development in chronic infections. Therefore, the combined treatment of 6-gingerol analog and tobramycin is suggested as a novel alternative for treating P. aeruginosa infections.
- Subjects :
- Microbiology (medical)
Physiology
medicine.drug_class
Antibiotics
Catechols
Virulence
tobramycin
Human pathogen
Respiratory Mucosa
medicine.disease_cause
Microbiology
biofilm
Cell Line
Drug Resistance, Multiple, Bacterial
Drug Resistance, Bacterial
Genetics
medicine
Tobramycin
Humans
Pseudomonas Infections
6-gingerol analog
Pathogen
Cell Proliferation
General Immunology and Microbiology
Ecology
Pseudomonas aeruginosa
business.industry
Biofilm
Quorum Sensing
Epithelial Cells
Cell Biology
infection
QR1-502
Anti-Bacterial Agents
Quorum sensing
Infectious Diseases
Biofilms
Fatty Alcohols
business
Research Article
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 21650497
- Volume :
- 9
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Microbiology Spectrum
- Accession number :
- edsair.doi.dedup.....4f2968247f42d535326af2f9d77d7dba