Article:Yarrowia lipolytica: a beneficious yeast in biotechnology as a rare opportunistic fungal pathogen: a minireview (6302869)

From ScienceSource
Jump to: navigation, search

This page is the ScienceSource HTML version of the scholarly article described at https://www.wikidata.org/wiki/Q60942021. Its title is Yarrowia lipolytica: a beneficious yeast in biotechnology as a rare opportunistic fungal pathogen: a minireview and the publication date was 2018-12-21. The initial author is Bartłomiej Zieniuk.

Fuller metadata can be found in the Wikidata link, which lists all authors, and may have detailed items for some or all of them. There is further information on the article in the footer below. This page is a reference version, and is protected against editing.



Converted JATS paper:

Journal Information

Title: World Journal of Microbiology & Biotechnology

Yarrowia lipolytica: a beneficious yeast in biotechnology as a rare opportunistic fungal pathogen: a minireview

  • Bartłomiej Zieniuk
  • Agata Fabiszewska

Publication date (epub): 12/2018

Publication date (pmc-release): 12/2018

Publication date (ppub): /2019

Abstract

Yarrowia lipolytica is one of the most studied “non-conventional” yeast species capable of synthesizing a wide group of valuable metabolites, in particular lipases and other hydrolytic enzymes, microbial oil, citric acid, erythritol and γ-decalactone. Processes based on the yeast have GRAS status (“generally recognized as safe”) given by Food and Drug Administration. The majority of research communications regarding to Y. lipolytica claim that the yeast species is non-pathogenic. In spite of that, Y. lipolytica, like other fungal species, can cause infections in immunocompromised and critically ill patients. The yeast possess features that facilitate invasion of the host cell (particularly production of hydrolytic enzymes), as well as the protection of the own cells, such as biofilm formation. The aim of this study was to present well-known yeast species Y. lipolytica as a rare opportunistic fungal pathogen. Possible pathogenicity and epidemiology of this yeast species were discussed. Antifungal drugs susceptibility and increasing resistance to azoles in Y. lipolytica yeasts were also presented.

Electronic supplementary material

The online version of this article (10.1007/s11274-018-2583-8) contains supplementary material, which is available to authorized users.

Paper

Introduction

One of the latest World Health Organization (WHO) report shows a growing threat from antibiotic-resistant microorganisms (WHO report [74]). On the other hand fungal diseases are not less hazardous. The incidence of fungal diseases especially in critically ill patients is thought to be increasing most commonly involving Candida and Aspergillus species (Beed et al. [7]; Brown et al. [14]). Due to an increase of population of immunocompromised patients and use of antifungal drugs in prophylaxis there have been appeared, other than mentioned above, species of yeasts and molds which can cause severe health problems (Nucci and Marr [56]). The aim of this study was to present well-known yeast species Yarrowia lipolytica as a poorly known opportunistic fungal pathogen. Although Y. lipolytica has a long history of usage in food industry and an expanding biotechnological potential, the yeast species could be an example of a rare opportunistic fungal pathogen, which cause infections in premature newborns, immunocompromised and critically ill patients (Zhao et al. [76]). Although the first attempt to discuss safety of Y. lipolytica usage was made by Groenewald et al. ([32]), this review lists possible virulence factors and drug susceptibility in the light of scientific announcements from the last few years, which has not been summarized yet. Moreover, there was exploited the issue by listing all known cases of illness connected with the presence of Y. lipolytica yeast what was evidenced in 110 patients.

Yarrowia lipolytica —an overview

Yarrowia lipolytica is a member of the Ascomycota phylum. The yeast species was formerly named as Candida, Endomycopsis or Saccharomycopsis lipolytica. The generic name “Yarrowia” refers to David Yarrow, researcher from Delft Microbiology Laboratory (Netherlands), who has identified this genus. The species name “lipolytica” is associated with the ability of hydrolyzing lipids (Nicaud [53]). The complete genome of the Y. lipolytica E150 strain (CLIB99) was published in 2004 by the Génolevures Consortium. The size of the yeast genome is not constant for all wild and laboratory strains and ranges from 12.7 to 22.1 Mb. The Y. lipolytica genome encodes 6448 genes and the number of chromosomes ranges from 4 to 6 (Dujon et al. [21]). Yeast Y. lipolytica belongs to heterothallic species with spores of various conjugation types. The frequency of conjugation in natural isolates is very low and wild strains are mostly haploids (Barth and Gaillardin [6]; Kurtzman et al. [45]).

Yarrowia lipolytica is widespread in nature. It is isolated from dairy products, such as Camembert and Rokpol cheeses (Roostita and Fleett [63]; Szczepaniak and Wojtatowicz [68]), dry fermented sausages (Flores et al. [26]) and other environments with high content of fats or hydrocarbons, for example rancid margarine, oil-polluted soil and sea water, as the yeast is able to utilize hydrophobic substrates such as hydrocarbons, fatty acids and lipids (Hassanshahian et al. [33]; Krzyczkowska and Fabiszewska [44]). Secretion of lipases by these microorganisms results in lipolysis of triacylglycerols, and proteases hydrolyze proteins. These processes may be desirable in many technological processes, e.g. in creating the characteristic taste and shortening the ripening time, but on the other hand, uncontrolled development of these microorganisms may pose a threat to food quality, e.g. causing an unfavorable appearance and texture (Carreira et al. [15]; Groenewald et al. [32]).

The yeast is used as a model for the study of dimorphism, degradation of hydrophobic substrates, lipid metabolism, protein secretion and peroxisome biogenesis (Beopoulos et al. [9]; Fickers et al. [24]). It is capable of synthesizing a wide group of valuable metabolites, for example lipases, proteases and other hydrolytic enzymes, microbial oil with high content of unsaturated fatty acids, citric acid, erythritol and γ-decalactone (Krzyczkowska [43]; Fabiszewska et al. [22]; Papanikolaou and Aggelis [59]; Tomaszewska et al. [69]). Biotechnological processes based on the yeast species have GRAS (“generally recognized as safe”) status given by Food and Drug Administration (FDA) (Rywińska et al. [64]).

Interestingly, in 2009, the Polish company Skotan SA in cooperation with the Wrocław University of Environmental and Life Sciences, started the production of Y. lipolytica biomass (SCP, single cell protein) from waste glycerol and obtained registration of the feed in the European Union. There are also provided the researches on probiotic properties of the species (Rywińska et al. [64]). Only Amano Enzymes uses Y. lipolytica lipase in an enzyme preparation under the trade name Amano N-AP. In the past, enzymes from Y. lipolytica were used by Fluka, but they ceased their use due to the high thermolability and proteolytic enzyme content in the extract (Brígida et al. [13]). Recently, yeast Y. lipolytica can be used for making yeast dough for the feeding of stimulating bee colonies (Apiyarr preparation, Łysoń company, Poland) and the yeast are present in Biopuls preparation for vegetative and generative growth of plants by Micro-life company (Poland) (Londzin et al. [48]; http://www.biopuls.eu/index.php?page=original).

Epidemiology and pathogenicity of Yarrowia lipolytica

First Y. lipolytica (C. lipolytica) infection was reported in 1976 and it was ocular candidiasis (Nitzulescu and Niculescu [55]). Then in 1985 there was evidenced the first case of fungemia caused by Y. lipolytica. It was isolated from blood and intravenous catheter of a patient with recurrent fever (Wehrspann and Füllbrandt [72]). Moreover, Rajagopalan et al. ([62]) have reported first occurrence of vaginal colonization by Y. lipolytica in asymptomatic 25-year-old woman. Furthermore, case report by Boyd et al. ([12]) has shown that Y. lipolytica can cause cutaneous infection. 63-year-old immunocompetent woman had epidermal necrosis and minimal dermal inflammation due to yeast presence in her non-healing wound.

Infections due to Y. lipolytica have been increasingly described in persons which have been catheterizated for a long time (D’Antonio et al. [18]; Özdemir et al. [58]). Shin et al. ([65]) have described a nosocomial outbreak of Y. lipolytica fungemia in pediatric patients with central venous catheters. Use of broad-spectrum antibiotics, immunological and hematological disorders, parenteral nutrition and prolonged hospitalization are the main factors affecting development of the infection (Trabelsi et al. [70]). Trabelsi et al. ([70]) reported 55 cases of septicemia caused by Y. lipolytica occurred between October 2012 and June 2014 in the intensive care unit (ICU) in Tunisian hospital and after treatment 61.8% of patients have been cured. Y. lipolytica has been also isolated from nasopharynx, oropharynx, sputum and bronchial washing specimens, as well as from stool samples (Koivikko et al. [42]; Walsh et al. [71]).

Nevertheless, Y. lipolytica could be a part of an intestinal mycobiota, because it is isolated also from stool samples of healthy people (Gouba and Drancourt [31]). Irby et al. ([37]) have suggested that Y. lipolytica should be considered as normal flora of adult respiratory tract. Between 2000 and 2010 Y. lipolytica was isolated from 24 patients, which 17 isolates originated from lung tissues.

Supplementary Table 1 summarizes 110 cases of Y. lipolytica clinical isolates. The data comes from 22 scientific reports that appeared between 1976 and 2017 (Agarwal et al. [2]; Belet et al. [8]; Blanco et al. [11]; Chang et al. [16]; D’Antonio et al. [18]; Garcia-Martos et al. [28]; Gouba and Drancourt [31]; Irby et al. [37]; Kang et al. [39]; Koivikko et al. [42]; Lai et al. [46]; Levy et al. [47]; Mazumder et al. [49]; Ninin et al. [54]; Nitzulescu and Niculescu [55]; Özdemir et al. [58]; Rajagopalan et al. [62]; Shin et al. [65]; Trabelsi et al. [70]; Walsh et al. [71]; Wehrspann and Fullbrandt [72]; Ye et al. [75]; Zheng et al. [77]). The median age of the patients was 40 (patients were aged from 2 days old to 90 years old). Men accounted for 51.82% of cases (n = 57), woman 22.73% (n = 25), and in other cases there was no information about gender. There were only 6% of known patients under 3 years old (n = 83) and 5% of children between 4 and 10 years old. 31% of patients were between 41 and 60 years old and only 18% were above 60. Yeast isolates were recovered from blood (68.18%, n = 75), lungs (15.45%, n = 17), skin and wounds (5.45%, n = 6), eyes (3.64%, n = 3) and other clinical specimens such as: breast tissue, bronchoalveolar lavage fluid, duodenal mass, intraabdominal abscess, mesenteric mass, sinus aspirate, vagina and stool. When analysing the characteristics of patients in whom Y. lipolytica was isolated it can be noticed that usually there were no detected coinfections. In 15 of 29 described cases such coinfections were notified, most often by C. albicans (n = 6). Few other Candida species (n = 5), staphylococci (n = 4), streptococci (n = 2), E. coli (n = 2), M. tuberculosis (n = 2) and some other individual species were isolated together with Y. lipolytica colonies. In 6 patients more than one species was identified along with Yarrowia. There was noticed more than 50 different diseases in people from whom tissues Y. lipolytica was isolated. In 24.04% patients (n = 104) factor/disease underlying their weakness and infections was polytraumatism, for 18 patients (17.31%) it was surgery, for 16 patients (15.38%) diabetes, for 7 patients (7.69%) leukemia. If we look at fungal disease which were diagnosed in men from whom Y. lipolytica was isolated, the most usually identified disease entity was fungemia (51%) or both: fungemia and catheter-related candidemia (20%). Only one case of granuloma, cutaneous infection, vaginal colonization, ocular candidiasis and acute keratitis were described. Noteworthy, commonly the patients have catheter (88%, n = 82), which was in majority of cases not removed (90%, n = 60). This observations are in line with D’Antonio et al. ([18]), Özdemir et al. ([58]) and Trabelsi et al. ([70]). Predominantly amphotericin B and fluconazole were used to cure the patents, which 42.73% (n = 47) were cleared, and 32 (29.09%) patients died.

Virulence factors of Y. lipolytica

Despite the fact that Y. lipolytica is regarded as weakly pathogenic organism, these yeasts present a number of features that allow an effective invasion of the host organism. Hydrolytic enzymes are one of the major factors, which could affect the pathogenicity of Y. lipolytica. This fungus is able to produce wide range of hydrolases, such as: proteases, phospholipases and hemolysins, which help in the invasion of tissues (Abbes et al. [1]; Kantarcioglu and Yucel [40]). Phospholipases and proteases secreted by yeasts play an important role in the damage of cell membranes, which consist of lipids and proteins. Moreover, proteases are capable of degrading epithelial and mucosal components, for example collagen and keratin (Fotedar and Al-Hedaithy [27]). Additionally, the most common human fungal pathogen C. albicans and other non-albicans Candida uses proteolytic enzymes to degradation of antibodies, complement and cytokines (Monod et al. [51]). Similar mechanism may occur in Y. lipolytica yeasts, but further studies are needed. Y. lipolytica as a former member of the Candida genus is compared to C. albicans—the most frequently isolated fungal pathogen in humans. Due to high pathogenicity of that yeast species, C. albicans is a good example to comparison, despite that these two species are quite evolutionarily distant (Barns et al. [5]).

Kantarcioglu and Yucel ([40]) have examined 95 clinical Candida isolates and among these isolates four of them were Y. lipolytica yeasts. Three of four isolates showed protease activity and none of them showed phospholipase activity. In another research 58 Y. lipolytica isolates of blood, urine and vaginal origin were evaluated to produce hydrolytic enzymes in comparison with C. albicans and C. glabrata. 98.2% of Y. lipolytica isolates showed caseinase activity and only vaginal isolates showed phospholipase activity and the hemolytic activity between the three species showed no significant differences (Abbes et al. [1]).

Lipases are hydrolytic enzymes, which may also play its role during infections. Microbial lipases (EC 3.1.1.3) are widely used in food technology, organic chemistry and biotechnology. The lipolytic activity of Y. lipolytica for the first time was described by Peters and Nelson ([60]), but genes encoding lipase proteins have been discovered since 2000s (Pignède et al. [61]). Lipases and esterases of the Y. lipolytica species are coded by the lipase gene family - LIP and the major extracellular lipase protein is Lip2p, which is encoded by LIP2 gene (Fickers et al. [25]). Putative roles of extracellular lipases were discussed by Stehr et al. ([66]). The most important function of lipases secreted by microorganisms is lipid digestion and thanks to lipolysis the yeast could use hydrophobic carbon sources for growth. Utilization of unusual carbon sources by Y. lipolytica is frequently discussed topic by biotechnologists (Fickers et al. [24]). According to Stehr et al. ([66]) free fatty acids and other products of lipolysis (mono- and diacylglycerols) could affect different immune cells, initiate the inflammatory process and support adhesion to host cells.

Holzschu et al. ([34]) compared 11 yeasts species of industrial interest with C. albicans for their potential pathogenicity. Untreated and cortisone-treated mice were inoculated with yeasts, such as Y. lipolytica, S. cerevisiae and other Candida species. C. tropicalis caused infections similar to C. albicans. Other yeasts were not recovered after 6 days or recovered, but did not caused infections. In accordance to Y. lipolytica, authors suggested that maximum growth temperature of that yeasts is near 34 °C, therefore the species was not lethal or invasive for mice. Walsh et al. ([71]) checked the virulence of fungemia isolate of Y. lipolytica in murine model. Mice received different dilutions of yeasts via the lateral tail vein. All animals survived 14 days of experiment. Mouse which received the highest inoculum of Y. lipolytica had two abscesses in the left kidney and in the culture with kidney tissue that yeasts were present. Other tissues (brain, liver, spleen) were free of microbial contaminants and lesions. In comparison with Y. lipolytica, C. albicans caused mortality in all mice within the 2 week of experiment.

Adhesion to the host cells and hyphae formation can be also other significant virulence factors of the yeast species. Y. lipolytica is species of dimorphic yeast, which means that it grows as yeast-like cells or forms hyphae or pseudohyphae (Barth and Gaillardin [6]). Mechanism of dimorphic transition in Y. lipolytica is not well characterized, because filamentation of cells is a complex process. Over the years, scientists have published plenty of reports about factors and compounds affecting or inhibiting cells filamentation. It could be induced by carbon and nitrogen source, pH value, temperature, oxygenation and it’s also dependent on strain specificity (Kerkhoven et al. [41]). CLA4 gene is reported to play role in dimorphism of Y. lipolytica. It encodes Cla4 protein kinase, which is highly homologous to Cla4 protein kinases of C. albicans and S. cerevisiae. Deletion of CLA4 gene is not lethal, however, due to lack of this gene mutants of Y. lipolytica cannot form mycelium (Szabo [67]). Other genes involved in yeast-to-hyphae transition are YlRAC1 and YlBMH1. First of them encoding a G protein of the Rho family and the second encoding a 14-3-3 protein. Transcription levels of these genes increased during the yeast-to-hyphae transition (Hurtado et al. [36]; Hurtado and Rachubinski [35]). Moreover, Morales-Vargas et al. ([52]) have reported 61 up- and 165 downregulated genes involved in dimorphism, where some of these genes were homologous with S. cerevisiae.

Biofilm is a form of microbial community that is associated with a surface (Desai et al. [19]). Due to presence of extracellular matrix and complex structure, biofilms protect yeast cells against antifungal agents (Fanning and Mitchell [23]). D’Antonio et al. ([18]) reported that Y. lipolytica produced large amount of slime in glucose-based medium and that confirms the ability of biofilm production and also adhesion to and colonization of plastic central venous catheter. Abbes et al. ([1]) studied biofilm formation by Y. lipolytica in comparison with C. albicans and C. glabrata. Biofilms development have been examined in vitro (using 96-well polystyrene microtiter plates) as well as in vivo in a rat subcutaneous model. In contrast to Candida species, biofilms obtained by Y. lipolytica after catheter subcutaneous implementation seemed to be more compact hyphal layer and also number of cells was significantly greater.

Drug susceptibility of Yarrowia lipolytica

Antifungals are antimycotic drugs used to treat or prevent fungal diseases. These medications can be divided into the following classes: polyenes, azoles, echinocandins, and others. Polyenes, such as Amphotericin B and Nystatin bind to sterols in the cell membrane, mainly ergosterol, which causes disruption of the cell membrane integrity and resulting in leakage of ions and other cytoplasmic components and cell lysis (Odds et al. [57]). Azoles are the largest group of antifungal agents. The most common in clinical use are triazoles, such as Fluconazole and Itraconazole. Mechanism of their action is to inhibit 14a-demethylation of lanosterol in the ergosterol biosynthetic pathway (Ghannoum and Rice [29]). Echinocandins (Anidulafungin, Caspofungin and Micafungin) are inhibitors of glucan synthesis in the cell wall (Ghannoum and Rice [29]). Another used antifungal drug is Flucytosine, also known as 5-fluorocytosine. Flucytosine is converted inside fungal cell to 5-fluorouracil and other compounds, resulting in inhibition of DNA synthesis (Odds et al. [57]).

Antifungal susceptibility testing of the yeasts provides meaningful information for epidemiological, clinical and therapeutic issues. As mentioned before, Y. lipolytica was often isolated from patients with central venous catheters. In some cases, removal of central vein catheter in conjunction with an antifungal drug was the best way in treatment of catheter-related candidemia. On the other hand, sometimes catheter could not be removed due to patient’s condition or type of catheter. Antifungal-lock technique (ALT) was proposed as an alternative method for treatment of catheter-related infections. ALT consists of filling the catheter lumen with antimicrobials and leaving them for an appropriate period of time (Mermel et al. [50]). Özdemir et al. ([58]) reported first case of using ALT in combination with systemic therapy to treat Y. lipolytica fungemia. Intravenous caspofungin and caspofungin-lock therapy was initiated in 9-year-old patient with neuroblastoma. Solution of antifungal, dextrose and heparin was placed in the lines for 12 h. Cultures were negative after 4 days of treatment, and therapy was stopped after 14 days and no relapse was seen then.

A panel of experts of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) presented an overview of data on rare invasive yeast infections. Y. lipolytica was also mentioned in the report and authors claimed that clinical significance of that yeast species is uncertain and minimal inhibitory concentration (MIC) of fluconazole is higher than MIC obtained for C. albicans (Arendrup et al. [3]). MIC distribution of Yarrowia lipolytica isolates is presented in Table 1. The data comes from seven scientific reports (Blanco et al. [11]; D’Antonio et al. [18]; Diekema et al. [20]; Lai et al. [46]; Shin et al. [65]; Walsh et al. [71]; Zhao et al. [76]). Additionally, MIC50 and MIC90 values were calculated, which represents MIC values at which 50% or 90% of isolates in population are inhibited, respectively. Both MIC, MIC50 and MIC90 are important parameters in describing the susceptibility of isolates to antimicrobials.

Table 1

MIC distribution of Yarrowia lipolytica isolates

Antifungal classes Antifungal agent Number of isolates with MIC (µg/ml) of MIC50* MIC90* Observations
0.008 0.016 0.032 0.064 0.125 0.25 0.5 1 2 4 8 16 32 ≥ 64
Polyene antifungals Amphotericin B 7 22 19 6 4 1 1 2 59
Azole antifungals Ketoconazole 1 3 3 4 11
Fluconazole 1 2 3 14 15 1 2 5 8 4 > 64 51
Itraconazole 1 2 1 7 16 3 1 3 0.5 2 34
Posaconazole 1 3 3 12 5 4 1 3 0.5 4 32
Voriconazole 1 1 9 9 5 2 4 4 0.064 2 35
Echinocandins Anidulafungin 3 7 5 6 2 1 24
Caspofungin 1 1 7 12 9 1 0.25 0.5 31
Micafungin 1 2 8 8 5 24
Others 5-Fluorocytosine 1 3 4 3 6 17

*MIC50 and MIC90 values were calculated for antifungals with at least 30 observations

Zhao et al. ([76]) compared susceptibility of 14 Y. lipolytica isolates to 9 different antifungal drugs. All 14 isolates showed low MICs to echinocandins and amphotericin B, 4 isolates had MICs of < 4 µg/ml to flucytosine and susceptibility to azoles was more diverse, where MIC values for fluconazole were highest. Diekema et al. ([20]) examined the susceptibility of 658 clinical isolates of rare species of Candida yeasts (including 16 strains of Y. lipolytica) to amphotericin, fluconazole, posaconazole, voriconazole, anidulafungin, caspofungin and micafungin. Echinocandins and voriconazole exhibited highest activity against Y. lipolytica, and MICs of that antifungals were not higher than 2 µg/ml, but most of the tested strains were not susceptible to amphotericin B and fluconazole.

Barchiesi et al. ([4]) compared in vitro activity of five antifungals (fluconazole, itraconazole, ketoconazole, flucytosine and amphotericin B) against uncommon clinical isolates of Candida spp. Results showed that strains differ in susceptibility to antifungal agents. Among the tested strains authors identified a strain of Y. lipolytica, with low susceptible to fluconazole and also that strain was cross-resistant to ketoconazole and itraconazole. Sixty-seven percent of Y. lipolytica strains have been defined as isolates with reduced susceptibility to flucytosine, therefore that antifungal agent is rarely used in monotherapy of fungal infections.

The studies quoted above show that voriconazole, caspofungin, micafungin and anidulafungin may be better treatment options than fluconazole or 5-fluorocytosine. Results show also a phenomenon of increasing resistance to azoles. Mechanism of azole resistance occurring in Candida genus is associated with, among others, overexpression of CDR1 (Candida drug resistance gene), CDR2 (a homologue of CDR1) and MDR1 (multidrug resistance gene) genes, which encode efflux pumps, that are capable of transporting antifungal drugs out of the cell. Another mechanism is occurring a point mutations in genes encoding enzymes, which should be targeted by antifungal drug. Mutations in ERG11 gene (encoding lanosterol 14α-demethylase) prevent from biding azoles, resulting in a lack of inhibition of encoded enzyme, which is essential for ergosterol biosynthesis (major sterol found in cell membranes of fungi). Moreover, mutations can lead to overexpression of Erg11 protein, which increase resistance to azoles (Gołąbek et al. [30]; Whaley et al. [73]). Additionally, mutations in ERG3 gene (encoding Δ5,6-desaturase) can lead to accumulation of 14a-methylfecosterol in fungal membrane instead of ergosterol. As a result of reducing the amount of ergosterol in the membrane, resistance to azoles and polyenes increases (Kanafani and Perfect [38]). In the case of echinocandins resistance in C. albicans and other Candida spp., it results from point mutations in the FKS1 gene (involved in β-1,3-d-glucan synthesis). Substitution of amino acids in protein lead to elevating MIC value for echinocandins 5- to 100-fold (Cowen et al. [17]). Yeast can also be resistant to 5-fluorocytosine. This is due to the fact that mutations in cytosine deaminase and uracil phosphoribosyltransferase lead to defects in flucytosine metabolism what result in resistance to that antifungal drug (Ghannoum and Rice [29]). Mechanisms of resistance in Y. lipolytica have not been described yet, however, those listed above may also occur in this yeast species.

Conclusion

Yarrowia lipolytica is an yeast species phylogenetically distant from S. cerevisiae or other well-studied yeast species and known from its interesting physiological features. It is considered as a non-pathogenic microorganism and the U.S. Food and Drug Administration has given its metabolites the GRAS status. Moreover, the species is an inseparable element of the microflora accompanying many food products with a long history of occurrence in human diet. Nevertheless, in the light of the reviewed cases of yeast infections, Y. lipolytica may be also considered as a rare opportunistic fungal pathogen in patients with compromised immunity and those with catheters. Infections caused by this yeast species are very rare, however Y. lipolytica might be an epidemiological problem for critically ill patients in the future due to increasing resistance to antifungal drugs. The reported in the literature strains of Y. lipolytica differed in susceptibility to antifungal agents, mainly fluconazole and other azoles were investigated. In some cases mentioned in the review, infections were resolved without treatment, which may suggest low virulence of the species, therefore further studies are needed to compare the virulence of Y. lipolytica with other Candida spp. and to confirm its pathogenicity, as most of the yeast occurrences in patients were reported not earlier than 20 years ago. An interesting issue are virulence factors of Y. lipolytica, which have been proposed in the review. With a lot of certainty occurrence of Y. lipolytica infections yet do not cross with its usage in various industries as a microorganism with a huge biotechnological potential, but the pathogenicity of each foodborne microorganism should be monitored up to date.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 485 KB)

References

  1. S AbbesI AmouriH TrabelsiS NejiH SellamiF RahmouniF MakniT RebaiA AyadiAnalysis of virulence factors and in vivo biofilm-forming capacity of Yarrowia lipolytica isolated from patients with fungemiaMed Mycol201755219320210.1093/mmy/myw02827440915
  2. S AgarwalK ThakurA KangaG SinghP GuptaCatheter-related candidemia caused by Candida lipolytica in a child with tubercular meningitisIndian J Pathol Microbiol20085129830010.4103/0377-4929.4170918603717
  3. MC ArendrupT BoekhoutM AkovaJF MeisOA CornelyO Lortholaryon behalf of the ESCMID EFISG study group and ECMMESCMID and ECMM joint clinical guidelines for the diagnosis and management of rare invasive yeast infectionsClin Microbiol Infect201420Suppl. 3769810.1111/1469-0691.1236024102785
  4. F BarchiesiAM TortoranoLF Di FrancescoM CogliatiG ScaliseMA VivianiIn vitro activity of five antifungal agents against uncommon clinical isolates of Candida sppJ Antimicrob Chemother199943229529910.1093/jac/43.2.29511252339
  5. SM BarnsDJ LaneML SoginC BibeauWG WeisburgEvolutionary relationships among pathogenic Candida Species and RelativesJ Bacteriol199117372250225510.1128/jb.173.7.2250-2255.19912007550
  6. G BarthC GaillardinPhysiology and genetics of the dimorphic fungus Yarrowia lipolyticaFEMS Microbiol Rev199719421923710.1111/j.1574-6976.1997.tb00299.x9167256
  7. M BeedR ShermanS HoldenFungal infections and critically ill adultsContin Educ Anaesth Crit Care Pain201414626226710.1093/bjaceaccp/mkt067
  8. N BeletE CiftçiE InceN DalgiçS OncelH GürizA YagmurluH DindarU DoğruCaspofungin treatment in two infants with persistent fungemia due to Candida lipolyticaScand J Infect Dis2006386–755956210.1080/0036554050040405216798714
  9. A BeopoulosT ChardotJM NicaudYarrowia lipolytica: A model and a tool to understand the mechanisms implicated in lipid accumulationBiochimie200991669210.1016/j.biochi.2009.02.00419248816
  10. Biopuls Original Preparation by Microlife sp. z o.o. http://www.biopuls.eu/index.php?page=original. Accessed 15 Sept 2018
  11. MT BlancoP Garcia-MartosA Garcia-TapiaC FernandezJ NavarroF GuerreroFungemia por Candida lipolytica: a proposito de 2 casosRev Iberoam Micol200926321121210.1016/j.riam.2009.02.00419635447
  12. AS BoydL WhelessBG BradyD EllisCutaneous Yarrowia lipolytica infection in an immunocompetent womanJAAD Case Rep201714321922110.1016/j.jdcr.2017.02.010
  13. AIS BrígidaPFF AmaralMAZ CoelhoLRB GonÒ«alvesLipase from Yarrowia lipolytica: production, characterization and application as an industrial biocatalystJ Mol Catal B201410114815810.1016/j.molcatb.2013.11.016
  14. GD BrownDW DenningNAR GowSM LevitzMG NeteaTC WhiteHidden killers: human fungal infectionsSci Transl Med20124165165rv1310.1126/scitranslmed.300440423253612
  15. A CarreiraL PalomaV LoureiroPigment producing yeasts involved in the brown surface discoloration of ewes’ cheeseInt J Food Microbiol19984122323010.1016/S0168-1605(98)00054-39706790
  16. CL ChangTH ParkEY LeeYK LimHC SonRecurrent self-limited fungemia caused by Yarrowia lipolytica in a patient with acute myelogenous leukemiaJ Clin Microbiol20013931200120110.1128/JCM.39.3.1200-1201.200111230460
  17. LE CowenD SanglardSJ HowardPD RogersDS PerlinMechanisms of antifungal drug resistanceCold Spring Harb Perspect Med201557a01975210.1101/cshperspect.a019752
  18. D D’AntonioF RomanoE PontieriG FiortoniC CaraccioloS BianchiniP OliosoT StanisciaR SferraS BocciaA VetuschiG FedericoE GaudioG CarrubaCatheter-related candidemia caused by candida lipolytica in a patient receiving allogeneic bone marrow transplantationJ Clin Microbiol20024041381138610.1128/JCM.40.4.1381-1386.200211923360
  19. JV DesaiAP MitchellDR AndesFungal biofilms, drug resistance, and recurrent infectionCold Spring Harb Perspect Med2014410a01972910.1101/cshperspect.a01972925274758
  20. DJ DiekemaSA MesserLB BoykenRJ HollisJ KroegerS TendolkarMA PfallerIn vitro activity of seven systemically active antifungal agents against a large global collection of rare candida species as determined by CLSI broth microdilution methodsJ Clin Microbiol200947103170317710.1128/JCM.00942-0919710283
  21. B DujonD ShermanG FischerP DurrensS CasaregolaI LafontaineJ De MontignyC MarckC NeuvegliseE TallaN GoffardL FrangeulM AigleV AnthouardA BabourV BarbeS BarnayS BlanchinJM BeckerichE BeyneC BleykastenA BoisrameJ BoyerL CattolicoF ConfanioleriA DaruvarL de DesponsE FabreC FairheadH Ferry-DumazetA GroppiF HantrayeC HennequinN JauniauxP JoyetR KachouriA KerrestR KoszulM LemaireI LesurL MaH MullerJ-M NicaudM NikolskiS OztasO Ozier-KalogeropoulosS PellenzS PotierGF RichardML StraubA SuleauD SwennenF TekaiaM Wesolowski-LouvelE WesthofB WirthM Zeniou-MeyerI ZivanovicM Bolotin-FukuharaA ThierryC BouchierB CaudronC ScarpelliC GaillardinJ WeissenbachP WinckerJL SoucietGenome evolution in yeastsNature2004430354410.1038/nature0257915229592
  22. AU FabiszewskaIA StolarzewiczWM ZamojskaE Białecka-FlorjańczykCarbon source impact on Yarrowia lipolytica KKP 379 lipase productionAppl Biochem Micro201450440441010.1134/S000368381404005X
  23. S FanningAP MitchellFungal biofilmsPLoS Pathog201284e100258510.1371/journal.ppat.100258522496639
  24. P FickersPH BenettiY WachéA MartyS MauersbergerMS SmitJM NicaudHydrophobic substrate utilisation by the yeast Yarrowia lipolytica, and its potential applicationsFEMS Yeast Res200556–752754310.1016/j.femsyr.2004.09.00415780653
  25. P FickersA MartyJM NicaudThe lipases from Yarrowia lipolytica: genetics, production, regulation, biochemical characterization and biotechnological applicationsBiotechnol Adv201129663264410.1016/j.biotechadv.2011.04.00521550394
  26. M FloresS CorralL Cano-GarcíaA SalvadorC BellochYeast strains as potential aroma enhancers in dry fermented sausagesInt J Food Microbiol2015212162410.1016/j.ijfoodmicro.2015.02.02825765533
  27. R FotedarSS Al-HedaithyComparison of phospholipase and proteinase activity in Candida albicans and C. dubliniensisMycoses2005481626710.1111/j.1439-0507.2004.01057.x15679669
  28. P García-MartosF de la RubiaMJ PalomoMM AlvarezP MarinJ MiraCandida lipolytica, a new opportunistic pathogenEnferm Infecc Microbiol Clin19931131638499519
  29. MA GhannoumLB RiceAntifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistanceClin Microbiol Rev199912450151710.1128/CMR.12.4.50110515900
  30. K GołąbekJA StrzelczykA OwczarekP CuberA Ślemp-MigielA WiczkowskiSelected mechanisms of molecular resistance of Candida albicans to azole drugsActa Biochim Pol201562224725110.18388/abp.2014_94025901298
  31. N GoubaM DrancourtDigestive tract mycobiota: a source of infectionMed Mal Infect2015451–291610.1016/j.medmal.2015.01.00725684583
  32. M GroenewaldT BoekhoutC NeuvegliseC GaillardinPWM van DijckM WyssYarrowia lipolytica: safety assessment of an oleaginous yeast with a great industrial potentialCrit Rev Microbiol201440318720610.3109/1040841X.2013.77038623488872
  33. M HassanshahianH TebyanianS CappelloIsolation and characterization of two crude oil-degrading yeast strains, Yarrowia lipolytica PG-20 and PG-32, from the Persian GulfMar Pollut Bull20126471386139110.1016/j.marpolbul.2012.04.02022622152
  34. DL HolzschuFW ChandlerL AjelloDG AhearnEvaluation of industrial yeasts for pathogenicitySabouraudia1979171717810.1080/00362177985380091441902
  35. CA HurtadoRA RachubinskiYlBMH1 encodes a 14-3-3 protein that promotes filamentous growth in the dimorphic yeast Yarrowia lipolyticaMicrobiology20021483725373510.1099/00221287-148-11-372512427962
  36. CA HurtadoJM BeckerichC GaillardinRA RachubinskiA rac homolog is required for induction of hyphal growth in the dimorphic yeast Yarrowia lipolyticaJ Bacteriol200018292376238610.1128/JB.182.9.2376-2386.200010762235
  37. RF IrbyM KandulaR ZadikanyRL SandinJN GreeneYarrowia lipolytica as normal human flora: a case series of 24 patients with positive cultures and no attributable diseaseInfect Dis Clin Pract201422420720910.1097/IPC.0000000000000106
  38. ZA KanafaniJR PerfectResistance to antifungal agents: mechanisms and clinical impactClin Infect Dis200846112012810.1086/52407118171227
  39. KW KangHJ YoonSH JungSH ChoHY KimYW YooA case of Yarrowia lipolytica fungemia after raw beef ingestionKorean J Med2008745566569
  40. AS KantarciogluA YücelPhospholipase and protease activities in clinical Candida isolates with reference to the sources of strainsMycoses2002455–616016510.1046/j.1439-0507.2002.00727.x12100532
  41. EJ KerkhovenKR PomraningSE BakerJ NielsenRegulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolyticaNPJ Syst Biol Appl201621600510.1038/npjsba.2016.528725468
  42. A KoivikkoK KalimoE NieminenM VianderRelationship of immediate and delayed hypersensitivity to nasopharyngeal and intestinal growth of Candida albicans in allergic subjectsAllergy198843320120510.1111/j.1398-9995.1988.tb00419.x3287998
  43. J KrzyczkowskaThe use of castor oil in the production of γ-decalactone by Yarrowia lipolytica KKP 379Chem Technol2012361586110.5755/j01.ct.61.3.2717
  44. J KrzyczkowskaAU FabiszewskaYarrowia lipolytica - Niekonwencjonalne drożdże w biotechnologiiPost Mikrobiol20155413343
  45. CP KurtzmanJW FellT BoekhoutThe yeasts: a taxonomic study20115AmsterdamElsevier
  46. CC LaiMR LeeCH HsiaoCK TanSH LinCH LiaoYT HuangPR HsuehInfections caused by Candida lipolyticaJ Infection201265437237410.1016/j.jinf.2012.06.011
  47. JM LevyRS LevinJT ClancyLower-extremity wounds inflicted by ratsJ Am Podiat Med Assn2003931586110.7547/87507315-93-1-58
  48. W LondzinK BuczekM ZonZastosowanie drożdży Yarrowia lipolytica jako immunostymulującej paszy białkowej dla pszczółPasieka201543034
  49. SA MazumderWA ToddKO ClevelandFatal Yarrowia lipolytica intra-abdominal abscess with persistent fungemia in a liver transplant recipientInfect Dis Clin Pract20152327327510.1097/IPC.0000000000000251
  50. LA MermelBM FarrRJ SherertzII RaadN O’GradyJS HarrisDE CravenGuidelines for the management of intravascular catheter-related infectionsClin Infect Dis2001321249127210.1086/32000111303260
  51. M MonodS CapocciaB LéchenneC ZauggM HoldomO JoussonSecreted proteases from pathogenic fungiInt J Med Microbiol20022925–640541910.1078/1438-4221-0022312452286
  52. AT Morales-VargasA DomínguezJ Ruiz-HerreraIdentification of dimorphism-involved genes of Yarrowia lipolytica by means of microarray analysisRes Microbiol2012163537838710.1016/j.resmic.2012.03.00222595080
  53. JM NicaudYarrowia lipolyticaYeast20122940941810.1002/yea.292123038056
  54. E NininO MorinLE TortorecN MilpiedP MoreauJL HarousseauInfection invasive à Candida lipolytica après allogreffe de moelle osseuseJ Mycol Med19977212214
  55. V NitzulescuM NiculescuThree cases of ocular candidiasis caused by Candida lipolyticaArch Roum Pathol Exp Microbiol19763532692721021048
  56. M NucciKA MarrEmerging fungal diseasesClin Infect Dis200541452152610.1086/43206016028162
  57. FC OddsAJP BrownNAR GowAntifungal agents: mechanisms of actionTRENDS Microbiol200311627227910.1016/S0966-842X(03)00117-312823944
  58. H ÖzdemirA KarbuzE ÇiftçiHU DinçaslanE İnceD AysevG YavuzÜ DoğruSuccessful treatment of central venous catheter infection due to Candida lipolytica by caspofungin-lock therapyMycoses201154564764910.1111/j.1439-0507.2010.01964.x
  59. S PapanikolaouG AggelisLipids of oleaginous yeasts. Part I: Biochemistry of single cell oil productionEur J Lipid Sci Technol20111131031105110.1002/ejlt.201100014
  60. II PetersFE NelsonPreliminary characterization of the lipase of mycotorula lipolyticaJ Bacteriol194855559360016561496
  61. G PignèdeH WangF FudalejC GaillardinM SemanJM NicaudCharacterization of an extracellular lipase encoded by LIP2 in Yarrowia lipolyticaJ Bacteriol2000182102802281010.1128/JB.182.10.2802-2810.200010781549
  62. B RajagopalanMS MathewsM JacobVaginal colonisation by Candida lipolyticaGenitourin Med19967221461478698369
  63. R RoostitaGH FleettThe occurrence and growth of yeasts in Camembert and blue-veined cheesesInt J Food Microbiol199628339340410.1016/0168-1605(95)00018-68652347
  64. A RywińskaP JuszczykM WojtatowiczM RobakZ LazarL TomaszewskaW RymowiczGlycerol as a promising substrate for Yarrowia lipolytica biotechnological applicationsBiomass Bioenerg20134814816610.1016/j.biombioe.2012.11.021
  65. JH ShinH KookDH ShinTJ HwangM KimSP SuhDW RyangNosocomial cluster of Candida lipolytica fungemia in pediatric patientsEur J Clin Microbiol Infect Dis200019534434910.1007/s10096005049110898134
  66. F StehrM KretschmarC KrögerB HubeW SchäferMicrobial lipases as virulence factorsJ Mol Catal B Enzym2003225–634735510.1016/S1381-1177(03)00049-3
  67. R SzaboCla4 protein kinase is essential for filament formation and invasive growth of Yarrowia lipolyticaMol Genet Genomics2001265117217910.1007/s00438000040511370864
  68. G SzczepaniakM WojtatowiczDobór szczepów Yarrowia lipolytica i Debaryomyces hansenii do szczepionki wspomagającej proces dojrzewania seraŻywność Nauka Technologia Jakość2011679192203
  69. L TomaszewskaM RakickaW RymowiczA RywińskaA comparative study on glycerol metabolism to erythritol and citric acid in Yarrowia lipolytica yeast cellsFEMS Yeast Res201414696697610.1111/1567-1364.1218425041612
  70. H TrabelsiK ChtaraN KhemakhemS NéjiF CheikhrouhouH SellamiR GuidaraF MakniM BouazizA AyadiFungemia caused by Yarrowia lipolyticaMycopathologia20151795–643744510.1007/s11046-015-9859-425614084
  71. TJ WalshIF SalkinDM DixonNJ HurdClinical, microbiological, and experimental animal studies of Candida lipolyticaJ Clin Microbiol19892759279312745702
  72. P WehrspannU FullbrandtReport of a case of Yarrowia lipolytica (Wickerham et al.) van der Walt and von Arx isolated from a blood cultureMykosen198528521722210.1111/j.1439-0507.1985.tb02119.x4010700
  73. SG WhaleyEL BerkowJM RybakAT NishimotoKS BarkerPD RogersAzole antifungal resistance in Candida albicans and emerging non-albicans Candida speciesFront Microbiol20177217310.3389/fmicb.2016.0217328127295
  74. WHOPrioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis (WHO/EMP/IAU/2017.12)2017GenevaWorld Health Organization
  75. Q YeX XuJ LiH CaoFungemia caused by Yarrowia lipolytica in a patient with acute lymphoblastic leukemiaJ Pediatr Hematol Oncol201133e120e12110.1097/MPH.0b013e3181f53dbb21383637
  76. Y ZhaoJF ChanCC TsangH WangD GuoY PanY XiaoN YueJH ChenSK LauY XuPC WooClinical characteristics, laboratory identification, and in vitro antifungal susceptibility of Yarrowia (Candida) lipolytica isolates causing Fungemia: a multicenter, prospective surveillance studyJ Clin Microbiol2015531136394510.1128/JCM.01985-15
  77. YC ZhengJS ZengJW LiDJ WangYQ WuY WuGranuloma caused by Candida lipolytica in China: first case reportJ Clin Dermatol2009381911
The underlying source XML for this text is taken from https://www.ebi.ac.uk/europepmc/webservices/rest/PMC6302869/fullTextXML. The license for the article is Creative Commons Attribution 4.0 International. The main subject has been identified as Opportunistic infection.