Catechol, a Natural Allelochemical Thwarts Virulent Dimorphism in Candida Albicans and Potentiates the Antifungal Efficacy of Azoles and Polyenes.

Jothi, R. Anandha; Sangavi, Ravichellam; Kumar, Ponnuchamy; Shunmugiah, Karutha Pandian; Gowrishankar, Shanmugaraj

doi:10.21203/rs.3.rs-668716/v1

Cited by 3 publications

(3 citation statements)

References 38 publications

(57 reference statements)

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“…Catechol, while unable to inhibit Candida itself, potentiates the antifungal activity of azoles and polyenes, and prevents up-regulation of virulence-associated genes. Curiously, catechol did not reduce the viability of Candida biofilms, but did reduce their hydrophobicity [300].…”

Section: Azole Synergy With Natural Productsmentioning

confidence: 93%

Augmenting Azoles with Drug Synergy to Expand The Antifungal Toolbox

Kane¹,

Carter²

2022

Preprint

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Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal ar-senal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to re-sistance like active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosag-es, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strate-gies.

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Section: Azole Synergy With Natural Productsmentioning

confidence: 93%

Augmenting Azoles with Drug Synergy to Expand The Antifungal Toolbox

Kane¹,

Carter²

2022

Preprint

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“…For the fluorescence microscopy, a live-dead stain assay was performed by following previously described protocol by Ravi et al 27 . The slides were washed with sterile PBS, stained with 0.1% of acridine orange (AO) and ethidium bromide (EtBr) (1:1) (Sigma Aldrich) under dark conditions for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Two novel phages PSPa and APPa inhibit planktonic, sessile and persister populations of Pseudomonas aeruginosa, and mitigate its virulence in Zebrafish model

Karthika,

Malligarjunan,

Jothi

et al. 2023

Sci Rep

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The present study explores the avenue of phage therapy as an alternative antimicrobial therapeutic approach to counter multidrug-resistant (MDR) Pseudomonas aeruginosa infection. Our study investigated two novel virulent phages PSPa and APPa, specific to P. aeruginosa, in which in vitro evaluations were carried out to assess the therapeutic potential of phages. Both the identified phages exhibited host specificity by showing antagonistic activity of about 96.43% (27/28) and 92.85% (26/28) towards the 28 MDR clinical isolates of P. aeruginosa. The PSPa phage was found to have linear dsDNA with a sequence length of 66,368 bp and 92 ORFs, of which 32 were encoded for known functions of the phage life cycle and the remaining 60 were hypothetical functions. The APPa phage was found to have linear dsDNA with 59,591 bp of genome length and 79 ORFs, of which 15 were found to have known phage functions and the remaining 64 were found to be hypothetical proteins. Notably, the genome of both the phages lacks genes coding for tRNA, rRNA, and tmRNA. The phylogenetic analysis revealed that PSPa and APPa share > 95% sequence similarity with previously sequenced Pseudomonas viruses of their respective families. Further, the in vivo efficacy evaluation using the zebrafish model revealed that the treatment with PSPa and APPa has remarkably improved the survival rate of bacterial-infected zebrafish, reinforcing the anti-infective potential of the isolated phages PSPa and APPa against P. aeruginosa infection.

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“…Catechol, when applied in concentrations of 2–256 μg/mL, could dose-dependently inhibit biofilm and hyphal formation of C. albicans , it also inhibited virulence factors secreted hydrolases and reduced EPS levels in biofilm matrix. The qPCR data indicated that catechol application induces significant down-regulation of RAS1 , HWP1, and ALS3 , genes linked with the fungal pathogenesis [ 69 ].…”

Section: Recent Update On Antifungal Targets and Strategiesmentioning

confidence: 99%

Emerging Antifungal Targets and Strategies

Ivanov

Ćirić

Stojković

2022

IJMS

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Despite abundant research in the field of antifungal drug discovery, fungal infections remain a significant healthcare burden. There is an emerging need for the development of novel antifungals since those currently available are limited and do not completely provide safe and secure protection. Since the current knowledge regarding the physiology of fungal cells and the infection mechanisms is greater than ever, we have the opportunity to use this for the development of novel generations of antifungals. In this review, we selected and summarized recent studies describing agents employing different antifungal mechanisms. These mechanisms include interference with fungal resistance, including impact on the efflux pumps and heat shock protein 90. Additionally, interference with virulence factors, such as biofilms and hyphae; the impact on fungal enzymes, metabolism, mitochondria, and cell wall; and antifungal vaccines are explored. The agents investigated belong to different classes of natural or synthetic molecules with significant attention given also to plant extracts. The efficacy of these antifungals has been studied mainly in vitro with some in vivo, and clinical studies are needed. Nevertheless, there is a large quantity of products employing novel antifungal mechanisms that can be further explored for the development of new generation of antifungals.

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Catechol, a Natural Allelochemical Thwarts Virulent Dimorphism in Candida Albicans and Potentiates the Antifungal Efficacy of Azoles and Polyenes.

Cited by 3 publications

References 38 publications

Augmenting Azoles with Drug Synergy to Expand The Antifungal Toolbox

Augmenting Azoles with Drug Synergy to Expand The Antifungal Toolbox

Two novel phages PSPa and APPa inhibit planktonic, sessile and persister populations of Pseudomonas aeruginosa, and mitigate its virulence in Zebrafish model

Emerging Antifungal Targets and Strategies

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