Plagiochin E, an antifungal bis(bibenzyl), exerts its antifungal activity through mitochondrial dysfunction-induced reactive oxygen species accumulation in Candida albicans

Wu, Xintong; Cheng, Ai‐Xia; Sun, Libo; Sun, Song; Lou, Hongxiang

doi:10.1016/j.bbagen.2009.05.002

Cited by 90 publications

(66 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, several studies reported that ROS are both necessary and sufficient for inducing apoptosis in C. albicans , such as ROS induced by acetic acid [43], sugar-stress [44], salt-stress [45], plant antimicrobial peptide [46], hydrogen peroxide [47], farnesol [48], and plagiochin E [49]. These cases are commonly associated with the increase of ROS.…”

Section: Discussionmentioning

confidence: 99%

Alteramide B is a microtubule antagonist of inhibiting Candida albicans

Ding

et al. 2016

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Background Alteramide B (ATB), isolated from Lysobacter enzymogenes C3, was a new polycyclic tetramate macrolactam (PTM). ATB exhibited potent inhibitory activity against several yeasts, particularly Candida albicans SC5314, but its antifungal mechanism is unknown. Methods The structure of ATB was established by extensive spectroscopic analyses, including high-resolution mass spectrometry, 1D- and 2D-NMR, and CD spectra. Flow cytometry, fluorescence microscope, transmission electron microscope, molecular modeling, overexpression and site-directed mutation studies were employed to delineate the anti-candida molecular mechanism of ATB. Results ATB induced apoptosis in C. albicans through inducing reactive oxygen species (ROS) production by disrupting microtubules. Molecular dynamics studies revealed the binding patterns of ATB to the β-tubulin subunit. Overexpression of the wild type and site-directed mutants of the β-tubulin gene (TUBB) changed the sensitivity of C. albicans to ATB, confirming the binding of ATB to β-tubulin, and indicating that the binding sites are L215, L217, L273, L274 and R282. In vivo, ATB significantly improved the survival of the candidiasis mice and reduced fungal burden. Conclusion The molecular mechanism underlying the ATB-induced apoptosis in C. albicans is through inhibiting tubulin polymerization that leads to cell cycle arrest at the G2/M phase. The identification of ATB and the study of its activity provide novel mechanistic insights into the mode of action of PTMs against the human pathogen. General significance This study shows that ATB is a new microtubule inhibitor and a promising anti-Candida lead compound. The results also support β-tubulin as a potential target for anti-Candida drug discovery.

show abstract

Section: Discussionmentioning

confidence: 99%

Alteramide B is a microtubule antagonist of inhibiting Candida albicans

Ding

et al. 2016

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

show abstract

“…ROS accumulation and eventually apoptosis and/or necrosis in fungal pathogens has been demonstrated for several chemical compounds isolated from plants, such as shikonin from roots of Lithospermum erythrorhizon [76], medioresinol from stem bark of Sambucus williamsii [77], styraxjaponoside C from stem bark of Styrax japonica [78], amentoflavone from Selaginella tamariscina [79], dill seed essential oil (Anethum graveolens) [80,81], the polyphenol curcumin [82], plagiochin E from liverwort Marchantia polymorpha [83,84] and baicalein from Scutellaria baicaleinsis roots [85]. Moreover, the plant defensins HsAFP1 (Heuchera sanguinea), RsAFP2 (Raphinus sativus) and PvD1 (Phaseolus vulgaris), active against several yeast and fungal species were found to induce ROS accumulation in C. albicans and Fusarium oxysporum [86][87][88].…”

Section: Novel Ros-inducing Antifungal Agentsmentioning

confidence: 99%

Reactive Oxygen Species-Inducing Antifungal Agents and Their Activity Against Fungal Biofilms

2013

View full text Add to dashboard Cite

Invasive fungal infections are associated with very high mortality rates ranging from 20-90% for opportunistic fungal pathogens such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. Fungal resistance to antimycotic treatment can be genotypic (due to resistant strains) as well as phenotypic (due to more resistant fungal lifestyles, such as biofilms). With regard to the latter, biofilms are considered to be critical in the development of invasive fungal infections. However, there are only very few antimycotics, such as miconazole (azoles), echinocandins and liposomal formulations of amphotericin B (polyenes), which are also effective against fungal biofilms. Interestingly, these antimycotics all induce reactive oxygen species (ROS) in fungal (biofilm) cells. This review provides an overview of the different classes of antimycotics and novel antifungal compounds that induce ROS in fungal planktonic and biofilm cells. Moreover, different strategies to further enhance the antibiofilm activity of such ROS-inducing antimycotics will be discussed.

show abstract

“…These compounds arise biogenetically from lunularic acid or lunularin, which is widely distributed in leafy and thalloid liverworts [2]. Many of these compounds have a wide range of biological activities including anticancer, antibacterial and antifungal activities as well as decreases of cyclooxygenase, 5-lipoxygenase and calmodulin [3,4]. Marchantin C (Fig.…”

Section: Introductionmentioning

confidence: 98%