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Candida and invasive candidiasis: back to basics

Lim CS, Rosli R, Seow HF, Chong PP

Eur J Clin Microbiol Infect Dis, 2012 Jan;31(1):21-31.
PMID: 21544694 DOI: 10.1007/s10096-011-1273-3

The ubiquitous Candida spp. is an opportunistic fungal pathogen which, despite treatment with antifungal drugs, can cause fatal bloodstream infections (BSIs) in immunocompromised and immunodeficient persons. Thus far, several major C. albicans virulence factors have been relatively well studied, including morphology switching and secreted degradative enzymes. However, the exact mechanism of Candida pathogenesis and the host response to invasion are still not well elucidated. The relatively recent discovery of the quorum-sensing molecule farnesol and the existence of quorum sensing as a basic regulatory phenomenon of the C. albicans population behavior has revolutionized Candida research. Through population density regulation, the quorum-sensing mechanism also controls the cellular morphology of a C. albicans population in response to environmental factors, thereby, effectively placing morphology switching downstream of quorum sensing. Thus, the quorum-sensing phenomenon has been hailed as the 'missing piece' of the pathogenicity puzzle. Here, we review what is known about Candida spp. as the etiological agents of invasive candidiasis and address our current understanding of the quorum-sensing phenomenon in relation to virulence in the host.

Matched MeSH terms: Candida/physiology
Fulltext Effect of phenotypic switching on the biological properties and susceptibility to chlorhexidine in Candida krusei ATCC 14243

Arzmi MH, Abdul Razak F, Yusoff Musa M, Wan Harun WH

FEMS Yeast Res., 2012 May;12(3):351-8.
PMID: 22225549 DOI: 10.1111/j.1567-1364.2011.00786.x

Phenotypic switching is characterized as a virulence factor of Candida spp. This study was carried out to evaluate the phenotypic switching ability of C. krusei ATCC 14243 and to determine its effect on the biological properties, adherence capacity and susceptibility towards chlorhexidine digluconate (CHX). To induce switched generations C. krusei was cultured under nitrogen-depleted growth conditions by adding phloxine B. These phenotypically switched colonies were designated as the 1st generation. Subsequent sub-culturing was performed to produce the 2nd, 3rd and 4th switched generations. The recovery of the 3rd generation was the highest at 85.7% while that of the 4th generation was lower at 70.8%, and the recovery of the 1st and 2nd generations gradually reduced to 46.6% and 36.4%, respectively. All generations of C. krusei were susceptible towards CHX. The unswitched C. krusei was the most susceptible but the least adherent to coated hard surfaces. The 2nd generation was the least susceptible, but with the highest adherent ability. The minimum inhibition concentration and minimal fungicidal concentration of C. krusei of all generations were determined at 0.4 mg mL(-1) . These observations suggest that the switching activity of C. krusei induces changes to its biological properties and susceptibility towards CHX.

Matched MeSH terms: Candida/physiology*
Comparative Study of the Effects of Fluconazole and Voriconazole on Candida glabrata, Candida parapsilosis and Candida rugosa Biofilms

Madhavan P, Jamal F, Pei CP, Othman F, Karunanidhi A, Ng KP

Mycopathologia, 2018 Jun;183(3):499-511.
PMID: 29380188 DOI: 10.1007/s11046-018-0243-z

Infections by non-albicans Candida species are a life-threatening condition, and formation of biofilms can lead to treatment failure in a clinical setting. This study was aimed to demonstrate the in vitro antibiofilm activity of fluconazole (FLU) and voriconazole (VOR) against C. glabrata, C. parapsilosis and C. rugosa with diverse antifungal susceptibilities to FLU and VOR. The antibiofilm activities of FLU and VOR in the form of suspension as well as pre-coatings were assessed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction assay. Morphological and intracellular changes exerted by the antifungal drugs on Candida cells were examined by scanning electron microscope (SEM) and transmission electron microscope (TEM). The results of the antibiofilm activities showed that FLU drug suspension was capable of killing C. parapsilosis and C. rugosa at minimum inhibitory concentrations (MICs) of 4× MIC FLU and 256× MIC FLU, respectively. While VOR MICs ranging from 2× to 32× were capable of killing the biofilms of all Candida spp tested. The antibiofilm activities of pre-coated FLU were able to kill the biofilms at ¼× MIC FLU and ½× MIC FLU for C. parapsilosis and C. rugosa strains, respectively. While pre-coated VOR was able to kill the biofilms, all three Candida sp at ½× MIC VOR. SEM and TEM examinations showed that FLU and VOR treatments exerted significant impact on Candida cell with various degrees of morphological changes. In conclusion, a fourfold reduction in MIC50 of FLU and VOR towards ATCC strains of C. glabrata, C. rugosa and C. rugosa clinical strain was observed in this study.

Matched MeSH terms: Candida/physiology*
The inhibitory effects of aureobasidin A on Candida planktonic and biofilm cells

Tan HW, Tay ST

Mycoses, 2013 Mar;56(2):150-6.
PMID: 22882276 DOI: 10.1111/j.1439-0507.2012.02225.x

Aureobasidin A (AbA) is a cyclic depsipeptide antifungal compound that inhibits a wide range of pathogenic fungi. In this study, the in vitro susceptibility of 92 clinical isolates of various Candida species against AbA was assessed by determining the planktonic and biofilm MICs of the isolates. The MIC(50) and MIC(90) of the planktonic Candida yeast were 1 and 1 μg ml(-1), respectively, whereas the biofilm MIC(50) and MIC(90) of the isolates were 8 and ≥64 μg ml(-1) respectively. This study demonstrates AbA inhibition on filamentation and biofilm development of C. albicans. The production of short hyphae and a lack of filamentation might have impaired biofilm development of AbA-treated cells. The AbA resistance of mature Candidia biofilms (24 h adherent population) was demonstrated in this study.

Matched MeSH terms: Candida/physiology
Occurrence and characterization of Candida nivariensis from a culture collection of Candida glabrata clinical isolates in Malaysia

Tay ST, Lotfalikhani A, Sabet NS, Ponnampalavanar S, Sulaiman S, Na SL, et al.

Mycopathologia, 2014 Oct;178(3-4):307-14.
PMID: 25022264 DOI: 10.1007/s11046-014-9778-9

BACKGROUND: Candida nivariensis and C. bracarensis have been recently identified as emerging yeast pathogens which are phenotypically indistinguishable from C. glabrata. However, there is little data on the prevalence and antifungal susceptibilities of these species.
OBJECTIVE: This study investigated the occurrence of C. nivariensis and C. bracarensis in a culture collection of 185 C. glabrata isolates at a Malaysian teaching hospital.
METHODS: C. nivariensis was discriminated from C. glabrata using a PCR assay as described by Enache-Angoulvant et al. (J Clin Microbiol 49:3375-9, 2011). The identity of the isolates was confirmed by sequence analysis of the D1D2 domain and internal transcribed spacer region of the yeasts. The isolates were cultured on Chromogenic CHROMagar Candida (®) agar (Difco, USA), and their biochemical and enzymic profiles were determined. Antifungal susceptibilities of the isolates against amphotericin B, fluconazole, voriconazole and caspofungin were determined using E tests. Clotrimazole MICs were determined using a microbroth dilution method.
RESULTS: There was a low prevalence (1.1 %) of C. nivariensis in our culture collection of C. glabrata. C. nivariensis was isolated from a blood culture and vaginal swab of two patients. C. nivariensis grew as white colonies on Chromogenic agar and demonstrated few positive reactions using biochemical tests. Enzymatic profiles of the C. nivariensis isolates were similar to that of C. glabrata. The isolates were susceptible to amphotericin B, fluconazole, voriconazole and caspofungin. Clotrimazole resistance is suspected in one isolate.
CONCLUSION: This study reports for the first time the emergence of C. nivariensis in our clinical setting.

Matched MeSH terms: Candida/physiology
A study on Candida biofilm growth characteristics and its susceptibility to aureobasidin A

Munusamy K, Vadivelu J, Tay ST

Rev Iberoam Micol, 2018 03 12;35(2):68-72.
PMID: 29544734 DOI: 10.1016/j.riam.2017.07.001

BACKGROUND: Biofilm is known to contribute to the antifungal resistance of Candida yeasts. Aureobasidin A (AbA), a cyclic depsipeptide targeting fungal sphingolipid biosynthesis, has been shown to be effective against several Candida species.
AIMS: The aim of this study was to investigate Candida biofilm growth morphology, its biomass, metabolic activity, and to determine the effects of AbA on the biofilm growth.
METHODS: The biofilm forming ability of several clinical isolates of different Candida species from our culture collection was determined using established methods (crystal violet and XTT assays). The determination of AbA planktonic and biofilm MICs was performed based on a micro-broth dilution method. The anti-biofilm effect of AbA on Candida albicans was examined using field emission scanning electron microscope (FESEM) analysis.
RESULTS: A total of 35 (29.7%) of 118 Candida isolates were regarded as biofilm producers in this study. Candida parapsilosis was the largest producer, followed by Candida tropicalis and C. albicans. Two morphological variants of biofilms were identified in our isolates, with 48.6% of the isolates showing mainly yeast and pseudohyphae-like structures, while the remaining ones were predominantly filamentous forms. The biofilm producers were divided into two populations (low and high), based on the ability in producing biomass and their metabolic activity. Candida isolates with filamentous growth, higher biomass and metabolic activity showed lower AbA MIC50 (at least fourfold), compared to those exhibiting yeast morphology, and lower biomass and metabolic activity. The observation of filament detachment and the almost complete removal of biofilm from AbA-treated C. albicans biofilm in FESEM analysis suggests an anti-biofilm effect of AbA.
CONCLUSIONS: The variability in the growth characteristics of Candida biofilm cultures affects susceptibility to AbA, with higher susceptibility noted in biofilm cultures exhibiting filamentous form and high biomass/metabolic activity.

Matched MeSH terms: Candida/physiology