E-viri
-
Shahina, Zinnat
01/2021Dissertation
Candida albicans is one of the most common fungi associated with lifethreateninginfections. Treatment of the associated infections is often ineffective inthe light of resistance, and so there is an urgent need to discover novel antifungals.Rather than killing the fungal cells, which requires quite high specificity and canlead to the emergence of further resistance, inhibiting growth and virulence factorsin fungal cells represents a good alternative for the development of new antifungaldrugs. Recently, there has been a resurged interest in essential oils and theiractive components, in relation to their pharmacological properties. The primaryobjective of this research was to evaluate the antifungal activity of cinnamon barkand rosemary essential oils, along with its major components cinnamadehyde, and1,8-cineole, α-pinene, respectively, and two other common essential oilcomponents, namely eugenol and citral, against C. albicans. Despite many reportson the antimicrobial activities of essential oils, the results have been diverse andthe evaluation methods inconsistent.At higher essential oil concentrations, reactive oxygen species weregenerated, impacting a wide range of processes including cell membranedepolarization, vacuolar segregation, mitochondrial dysfunction, cell-cyclecheckpoint deficiency, and mitotic catastrophe, which resulted in C. albicans death.At lower fractional MICs, essential oils had a ROS-independent response thatinhibited mycelial growth and biofilm formation, which may be attributable todefects at the cell membrane. However, microtubule inhibition also plays a role inlimiting hyphal growth. I explored the microtubule defects and how they relate toKar3p, a member of the kinesin-14 family shown to be linked to microtubulestability. Interestingly, both tubulin and Kar3 protein was delocalized with essentialoil components exposure at levels for which endogenous ROS levels were normal.I further demonstrate that the level of Kar3 is associated with resistance andsusceptibility of C. albicans to essential oil components in both liquid and on solidgrowth media. All mutant strains grown on hyphae-inducing media in the presenceof essential oil components exhibited an enhanced tendency to form pseudohyphalcells, a common phenotype for the homozygous and heterozygous deletionstrains. Towards these ends, microtubule defects were linked with theoreticalbinding between essential oil components and α-tubulin and Kar3p adjacent tocofactor binding sites, consistent with experimentally observed hyphal defects andbiofilm inhibition. This study for the first time uncovers a new mode of essential oilmediatedmicrotubule defects, which does not follow the known mechanisms ofconventional microtubule inhibition. The essential oil components appear to impactC. albicans eventually giving rise to psuedohyphal formation, microtubule loss,hyphal and biofilm reduction.Since those essential oil components impact multiple Candida targets, theyshould be less susceptible to resistance. Further, many components showed antivirulence,and may represent an effective approach for inhibiting Candida,especially in the context of physically preventing Candida from entering its hostthrough catheters and prosthetics.
Avtor
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.