Inhibition of the TetK efflux-pump by the essential oil of Chenopodium ambrosioides L. and α-terpinene against Staphylococcus aureus IS-58

Limaverde, Paulo W.; Campina, Fábia F.; Cunha, Francisco Assis Bezerra da; Crispim, Francidalva D.; Figueredo, Fernando Gomes; Lima, Luciene Ferreira de; Oliveira-Tintino, Cícera Datiane de Morais; Matos, Yedda Maria Lobo Soares de; Morais-Braga, Maria Flaviana Bezerra; Menezes, Irwin Rose Alencar de; Balbino, Valdir Queiroz; Coutinho, Henrique Douglas Melo; Siqueira-Júnior, José P.; Almeida, Jackson R.G.S.; Tintino, Saulo Relison

doi:10.1016/j.fct.2017.02.031

Cited by 82 publications

(34 citation statements)

References 28 publications

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“…This indicated that LVO affects mainly the membrane permeability of KPC-KP cells without affecting the efflux system. A previous study by Limaverde et al (2017) showed that Chenopodium ambrosioides essential oil act as an effective efflux pump inhibitor 30 . The compound responsible for the inhibition was α-terpinene 30 .…”

Section: Discussionmentioning

confidence: 99%

“…A previous study by Limaverde et al (2017) showed that Chenopodium ambrosioides essential oil act as an effective efflux pump inhibitor 30 . The compound responsible for the inhibition was α-terpinene 30 . A consolidating review study of 28 plant-derived compounds identified compounds such as α-pinene, catechol, eugenol acetate and linoleic acid as efflux pump inhibitors 31 .…”

Section: Discussionmentioning

confidence: 99%

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Lavender essential oil induces oxidative stress which modifies the bacterial membrane permeability of carbapenemase producing Klebsiella pneumoniae

Yang

Yusoff

Thomas

et al. 2020

Sci Rep

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Misuse of antibiotics in the clinical and agricultural sectors has caused the emergence of multidrugresistant (MDR) Klebsiella pneumoniae which contributes a threat to human health. in this study, we assessed the feasibility of lavender essential oil (LVo) as an antimicrobial agent in combinatory therapy with meropenem in suppressing the growth of carbapenemase-producing K. pneumoniae (Kpc-Kp). Synergistic interactions between LVO and meropenem were detected, which significantly reduce the inhibitory concentration of both LVO and meropenem by 15 and 4-fold respectively. Comparative proteomic profiling identified a disruption in the bacterial membrane via oxidative stress that was indicated by loss of membrane and cytoplasmic proteins and the upregulation of oxidative regulators. As a proof of concept, zeta potential measurements showed a change in cell surface charge while outer membrane permeability measurement indicated an increase in membrane permeability following exposure to LVO. This was indicative of a disrupted outer membrane. Ethidium bromide influx/efflux assays demonstrated no significant efflux pump inhibition by LVO, and scanning electron microscopy revealed irregularities on the cell surface after exposure to LVo. oxidative stress was also detected with increased level of RoS and lipid peroxidation in LVo-treated cells. in conclusion, our data suggest that LVo induced oxidative stress in K. pneumoniae which oxidizes the outer membrane, enabling the influx of generated ROS, LVO and meropenem into the bacterial cells, causing damage to the cells and eventually death. Klebsiella pneumoniae, a Gram-negative rod-shaped bacterium is one of the leading causes of hospital acquired infections, and is especially implicated in bacterial pneumonia 1,2. Misuse of antibiotics in the clinical and agricultural sectors has brought about the emergence of multidrug-resistant (MDR) K. pneumoniae, which is a threat to human health, especially in vulnerable groups such as neonates, the elderly and the immunocompromised 3,4. Carbapenems are now considered as the last resort antibiotics for treating severe MDR K. pneumoniae infections. However, resistance towards carbapenems was soon documented in K. pneumoniae due to increased reliance upon this line of antibiotics 5,6. Carbapenem-resistant K. pneumoniae produces carbapenemase, the most evolved β-lactamase currently in evidence, which can inactivate almost all classes of β-lactam antibiotics 7,8. Other antibiotic resistance mechanisms such as the overproduction of class C beta-lactamases, expression of the MDR efflux pump or an ESBL coupled with bacterial membrane permeability defects are sufficient to confer a carbapenem resistance phenotype to K. pneumonia 9-11. It has been reported that certain isolated carbapenem-resistant K. pneumoniae overexpress AcrAB pumps which remove a variety of antibiotics that penetrate the bacterial cell wall and membranes 12,13. Another study confirmed reduction in expression of porin proteins which reduces

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lavender essential oil induces oxidative stress which modifies the bacterial membrane permeability of carbapenemase producing Klebsiella pneumoniae

Yang

Yusoff

Thomas

et al. 2020

Sci Rep

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“…Bacterial efflux systems are associated with major human health concerns as they are involved in the resistance of pathogenic bacteria such as S. aureus [ 64 – 66 ]. Previously, inhibition of efflux pumps by natural products has been found to improve the activity of antibiotics against S. aureus .…”

Section: Discussionmentioning

confidence: 99%

“…Previously, inhibition of efflux pumps by natural products has been found to improve the activity of antibiotics against S. aureus . For example, inhibition of the TetK efflux pump was reported with the essential oil of Chenopodium ambrosioides and its constituent α -terpinene against S. aureus IS-58 strain [ 66 ]. In the present study, two well-known EPIs (CCCP and CPZ) were used to assess the implication of efflux pumps in the resistance of the studied S. aureus strains to plant extracts.…”

Section: Discussionmentioning

confidence: 99%

Antistaphylococcal and Antibiotic Resistance Modulatory Activities of Thirteen Cameroonian Edible Plants against Resistant Phenotypes

Wamba

Mbaveng

Nayim

et al. 2018

International Journal of Microbiology

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Background In this study, 18 methanol extracts from Cameroonian edible plants were tested for their antibacterial activities against 26 strains of S. aureus; the role of efflux pumps in the resistance of tested bacteria and the antibiotic resistance-modulating activities against selected multidrug-resistant (MDR) phenotypes were also investigated. Methods Broth microdilution assay was used to evaluate the antibacterial activity, the role of efflux pumps, and the antibiotic resistance-modulating effects of plant extracts. Results Extracts from Dacryodes edulis seeds (DES) and Dacryodes edulis bark (DEB) were active against all 26 tested bacterial strains, within the minimal inhibitory concentration (MIC) range of 256–1024 µg/mL. MIC values varied from 64 to 1024 µg/mL against 96.2% of the 26 tested bacteria for Phaseolus vulgaris leaves (PVL), 92.3% for Azadirachta indica bark (AIB), Dacryodes edulis leaves (DEL), and Ricinodendron heudelotii leaves (RHL). The lowest MIC value of 64 µg/mL was obtained with the extract from Cucurbita maxima beans (CMB) against MRSA4 strain and from Uapaca guineensis bark (UGB) against MRSA9 strain. Bacterial efflux pump inhibitor (EPI), carbonyl cyanide m-chlorophenyl hydrazone (CCCP), improved the activity of DES and UGB as well as that of extracts from Hibiscus esculentus leaves (HEL) and Uapaca guineensis leaves (UGL) against resistant S. aureus strains. Antibiotic-modulating effects against more than 70% of the S. aureus strains tested were obtained when RHL (at MIC/2) was combined with CIP, ERY, and KAN (88.89%), CHL (88.89%), TET (77.78%), and STR (88.89%). Conclusion The present study demonstrated that the 13 tested plants had antistaphylococcal effects and that DES, HEL, UGL, and UGB could be used in combination with EPI to combat resistance to Staphylococcus aureus. Also, it demonstrated that some studied extracts and mostly RHL could be used as antibiotic resistance modulators to fight against resistant strains of S. aureus.

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“…The essential oil from Chenopodium ambrosioides L. leaves, a mixture rich in terpenes, was tested against SA IS-58 strains. When associated with tetracholine it interacted synergistically, thus being attributable to its phytochemical constituents [34]. Some sesquiterpene derivatives isolated from the Ferula ferulioides K. plant presented a potentiating effect for norfloxacin against the SA-1199B NorA pump expressing strain [35].…”

Section: Inhibitory Effect Over Pumps By Mic Reductionmentioning

confidence: 99%

Effect of α-Bisabolol and Its β-Cyclodextrin Complex as TetK and NorA Efflux Pump Inhibitors in Staphylococcus aureus Strains

et al. 2020

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Efflux pumps are proteins present in the plasma membrane of bacteria, which transport antibiotics and other compounds into the extracellular medium, conferring resistance. The discovery of natural efflux pump inhibitors is a promising alternative. α-Bisabolol is a sesquiterpene isolated from several plants such as Matricaria chamomilla L. and has important properties such as antibacterial and anti-inflammatory activity. Currently, the formation of inclusion complexes with β-Cyclodextrin has been used for improving the physicochemical characteristics of the host molecule. This study evaluated the effect of α-Bisabolol, in isolation and in complexation with β-Cyclodextrin, as TetK and NorA efflux pump inhibitors in Staphylococcus aureus strains. The minimum inhibitory concentration (MIC) was determined. Subsequently, inhibitory activity over the pumps was observed by an MIC reduction for the antibiotics, by using subinhibitory concentrations (MIC/8) in combination with tetracycline and norfloxacin. The MIC of the compounds was ≥1024 μg/mL. α-Bisabolol potentiated the action of tetracycline and reduced the MIC of norfloxacin to a clinically relevant concentration. The complexed substance showed synergism however, the effect of the isolated α-Bisabolol was superior to the complex. These results indicate α-Bisabolol is a potential substance to be used as an efflux pump inhibitor.

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Inhibition of the TetK efflux-pump by the essential oil of Chenopodium ambrosioides L. and α-terpinene against Staphylococcus aureus IS-58

Cited by 82 publications

References 28 publications

Lavender essential oil induces oxidative stress which modifies the bacterial membrane permeability of carbapenemase producing Klebsiella pneumoniae

Lavender essential oil induces oxidative stress which modifies the bacterial membrane permeability of carbapenemase producing Klebsiella pneumoniae

Antistaphylococcal and Antibiotic Resistance Modulatory Activities of Thirteen Cameroonian Edible Plants against Resistant Phenotypes

Effect of α-Bisabolol and Its β-Cyclodextrin Complex as TetK and NorA Efflux Pump Inhibitors in Staphylococcus aureus Strains

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