A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro.
The ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4081779?pdf=render |
id |
doaj-fc7cd95a82204dca83f120f250e3471c |
---|---|
record_format |
Article |
spelling |
doaj-fc7cd95a82204dca83f120f250e3471c2020-11-25T00:18:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10185910.1371/journal.pone.0101859A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro.Mikko T NieminenLily Novak-FrazerWilma RautemaaRanjith RajendranTimo SorsaGordon RamagePaul BowyerRiina RautemaaThe ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce significant levels of mutagenic acetaldehyde (ACH). ACH is also an important mediator of candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic acid (HICA) significantly inhibits planktonic growth of C. albicans. The aim of the present study was to investigate the effect of HICA on C. albicans biofilm formation and ACH production in vitro. Inhibition of biofilm formation by HICA, analogous control compounds or caspofungin was measured using XTT to measure biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were visualised by scanning electron microscopy (SEM). ACH levels were measured by gas chromatography. Transcriptional changes in the genes involved in ACH metabolism were measured using RT-qPCR. The mean metabolic activity and biomass of all pre-grown (4, 24, 48 h) biofilms were significantly reduced after exposure to HICA (p<0.05) with the largest reductions seen at acidic pH. Caspofungin was mainly active against biofilms pre-grown for 4 h at neutral pH. Mutagenic levels (>40 μM) of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no ACH production was detected from D-glucose in the presence of HICA at acidic pH (p<0.05). Expression of genes responsible for ACH catabolism was up-regulated by HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed hyphal structures during incubation with HICA at acidic pH. We conclude that HICA has potential as an antifungal agent with ability to inhibit C. albicans cell growth and biofilm formation. HICA also significantly reduces the mutagenic potential of C. albicans biofilms, which may be important when treating bacterial-fungal biofilm infections.http://europepmc.org/articles/PMC4081779?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mikko T Nieminen Lily Novak-Frazer Wilma Rautemaa Ranjith Rajendran Timo Sorsa Gordon Ramage Paul Bowyer Riina Rautemaa |
spellingShingle |
Mikko T Nieminen Lily Novak-Frazer Wilma Rautemaa Ranjith Rajendran Timo Sorsa Gordon Ramage Paul Bowyer Riina Rautemaa A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro. PLoS ONE |
author_facet |
Mikko T Nieminen Lily Novak-Frazer Wilma Rautemaa Ranjith Rajendran Timo Sorsa Gordon Ramage Paul Bowyer Riina Rautemaa |
author_sort |
Mikko T Nieminen |
title |
A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro. |
title_short |
A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro. |
title_full |
A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro. |
title_fullStr |
A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro. |
title_full_unstemmed |
A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro. |
title_sort |
novel antifungal is active against candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
The ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce significant levels of mutagenic acetaldehyde (ACH). ACH is also an important mediator of candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic acid (HICA) significantly inhibits planktonic growth of C. albicans. The aim of the present study was to investigate the effect of HICA on C. albicans biofilm formation and ACH production in vitro. Inhibition of biofilm formation by HICA, analogous control compounds or caspofungin was measured using XTT to measure biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were visualised by scanning electron microscopy (SEM). ACH levels were measured by gas chromatography. Transcriptional changes in the genes involved in ACH metabolism were measured using RT-qPCR. The mean metabolic activity and biomass of all pre-grown (4, 24, 48 h) biofilms were significantly reduced after exposure to HICA (p<0.05) with the largest reductions seen at acidic pH. Caspofungin was mainly active against biofilms pre-grown for 4 h at neutral pH. Mutagenic levels (>40 μM) of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no ACH production was detected from D-glucose in the presence of HICA at acidic pH (p<0.05). Expression of genes responsible for ACH catabolism was up-regulated by HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed hyphal structures during incubation with HICA at acidic pH. We conclude that HICA has potential as an antifungal agent with ability to inhibit C. albicans cell growth and biofilm formation. HICA also significantly reduces the mutagenic potential of C. albicans biofilms, which may be important when treating bacterial-fungal biofilm infections. |
url |
http://europepmc.org/articles/PMC4081779?pdf=render |
work_keys_str_mv |
AT mikkotnieminen anovelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT lilynovakfrazer anovelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT wilmarautemaa anovelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT ranjithrajendran anovelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT timosorsa anovelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT gordonramage anovelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT paulbowyer anovelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT riinarautemaa anovelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT mikkotnieminen novelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT lilynovakfrazer novelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT wilmarautemaa novelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT ranjithrajendran novelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT timosorsa novelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT gordonramage novelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT paulbowyer novelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro AT riinarautemaa novelantifungalisactiveagainstcandidaalbicansbiofilmsandinhibitsmutagenicacetaldehydeproductioninvitro |
_version_ |
1725377112292982784 |