Combined Treatment of 6-Gingerol Analog and Tobramycin for Inhibiting Pseudomonas aeruginosa Infections

Ham, So-Young; Kim, Hanshin; Jo, Min Jee; Lee, Jeong-Hoon; Byun, Youngjoo; Ko, Gang Jee; Park, Hee-Deung

doi:10.1128/spectrum.00192-21

Cited by 13 publications

(8 citation statements)

References 55 publications

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“…Many scholars attempted to develop and use non-traditional antibacterial drugs, such as antimicrobial peptides, bacteriophages, and plant extracts that had certain antibacterial and virulence and biofilm inhibition effects, in place of traditional antibacterial drugs ( Khan et al, 2021 ; Witherell et al, 2021 ). The QSIs can decrease the strain virulence factors, biofilm formation ability of the strain; therefore, they proved to be ideal for treatment purposes ( Ham et al, 2021 ). Substances such as quercetin, resveratrol, and 6-gingerol ( Quecan et al, 2019 ; Ham et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, QSIs can act as synergists in delaying antimicrobial resistance development. The combination of QSIs and antibacterial drugs can restore bacterial sensitivity to previously tolerated drugs, thus helping reduce the effective dose and improve the efficiency of antibacterial drugs ( Ham et al, 2021 ). Natural QSIs mainly exist in bacteria, fungi, animals, and plants, and marine organisms ( Kalia, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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Effects of chlorogenic acid on antimicrobial, antivirulence, and anti-quorum sensing of carbapenem-resistant Klebsiella pneumoniae

et al. 2022

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The rise in infections caused by the hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) is an emergent threat to public health. We assessed the effects of chlorogenic acid (CA), a natural phenolic compound, on antibacterial, antivirulence, and anti-quorum sensing (QS) of hv-CRKP. Five hv-CRKP were selected for antimicrobial susceptibility test and confirmed to carry virulence genes and carbapenem-resistant genes by polymerase chain reaction (PCR). Subsequently, a series of time-kill assay, determinations of protease activity and capsule content, biofilm-related experiment, scanning electron microscopy (SEM) and transmission electron microscope (TEM) observation, G. mellonella infection model, quantitative real-time PCR (qRT-PCR) of QS-related genes and biofilm formation genes, as well as AI-2 binding test were conduct to verify the effect of CA on hv-CRKP. Five CRKP strains showed varying degrees of resistance to antibacterial agents. All strains carried the blaKPC–2 gene, primarily carrying rmpA2, iucA, and peg-344. CA showed no effect on CRKP growth at the 1/2 minimum inhibitory concentration (MIC), 1/4 MIC, and 1/8 MIC, CA could reduce the production of extracellular protease and capsular polysaccharides, and improve the survival rate of larvae in Galleria mellonella (G. mellonella) infection model. By means of crystal violet staining and scanning electron microscopy experiments, we observed that CA can inhibit the formation of CRKP biofilm. On the quantitative real-time PCR analysis, the expression of the luxS, mrkA and wbbm genes in most CRKP strains appeared downregulated because of the CA treatment. Besides, CA significantly inhibited the effect of AI-2 activity of BB170. Our study suggests that CA can be an effective antimicrobial, antivirulent compound that can target QS in hv-CRKP infections, thus providing a new therapeutic direction for treating bacterial infections.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of chlorogenic acid on antimicrobial, antivirulence, and anti-quorum sensing of carbapenem-resistant Klebsiella pneumoniae

et al. 2022

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“…Recently, 6-gingerol has been reported to be an excellent addition to isoniazid for the treatment of tuberculosis due to its potent antimycobacterial and immunomodulatory effects against Mycobacterium tuberculosis [ 107 ]. A combination of 6-gingerol and tobramycin was proved very effective against P. aeruginosa , and therefore, holds prospects for clinical applications for the treatment of P. aeruginosa infections [ 108 ]. In addition, 6-gingerol possesses antiviral effects, specifically against the Chikungunya virus, by inhibiting its replication [ 109 ].…”

Section: Notable Bioactivitiesmentioning

confidence: 99%

Bioactive Compounds from the Zingiberaceae Family with Known Antioxidant Activities for Possible Therapeutic Uses

et al. 2022

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The Zingiberaceae family is a rich source of diverse bioactive phytochemicals. It comprises about 52 genera and 1300 species of aromatic flowering perennial herbs with characteristic creeping horizontal or tuberous rhizomes. Notable members of this family include ginger (Zingiber officinale Roscoe), turmeric (Curcuma longa L.), Javanese ginger (Curcuma zanthorrhiza Roxb.), and Thai ginger (Alpinia galanga L.). This review focuses on two main classes of bioactive compounds: the gingerols (and their derivatives) and the curcuminoids. These compounds are known for their antioxidant activity against several maladies. We highlight the centrality of their antioxidant activities with notable biological activities, including anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, antimicrobial, and anticancer effects. We also outline various strategies that have been applied to enhance these activities and make suggestions for research areas that require attention.

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“…Moreover, compound 43 displayed strong inhibition of biofilm formation in static and dynamic settings and the reduction of virulence factor production (elastase, rhamnolipid, and pyocyanin) in P. aeruginosa . In addition, compound 43 did not cause toxicity to human lung epithelial cells and alleviated the infectivity of P. aeruginosa in Tenebrio molitor larvae [ 44 ].…”

Section: Rhlr-targeted Modulatorsmentioning

confidence: 99%

Recent Advance in Small Molecules Targeting RhlR of Pseudomonas aeruginosa

et al. 2022

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Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic gram-negative pathogen that can cause various infections, particularly in patients with compromised host defenses. P. aeruginosa forms biofilms and produces virulence factors through quorum sensing (QS) network, resulting in resistance to antibiotics. RhlI/RhlR, one of key QS systems in P. aeruginosa, is considered an attractive target for inhibiting biofilm formation and attenuating virulence factors. Several recent studies examined small molecules targeting the RhlI/RhlR system and their in vitro and in vivo biological activities. In this review, RhlR-targeted modulators, including agonists and antagonists, are discussed with particular focus on structure-activity relationship studies and outlook for next-generation anti-biofilm agents.

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Combined Treatment of 6-Gingerol Analog and Tobramycin for Inhibiting Pseudomonas aeruginosa Infections

Abstract: 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.

Cited by 13 publications

References 55 publications

Effects of chlorogenic acid on antimicrobial, antivirulence, and anti-quorum sensing of carbapenem-resistant Klebsiella pneumoniae

Effects of chlorogenic acid on antimicrobial, antivirulence, and anti-quorum sensing of carbapenem-resistant Klebsiella pneumoniae

Bioactive Compounds from the Zingiberaceae Family with Known Antioxidant Activities for Possible Therapeutic Uses

Recent Advance in Small Molecules Targeting RhlR of Pseudomonas aeruginosa

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