Abstract
Strains of the Candida parapsilosis and Meyerozyma guilliermondii species complexes isolated from the internal tissues of 26 fruit species from 21 countries were evaluated for their susceptibility to conventional antifungal compounds (fluconazole, voriconazole, amphotericin B) and hydrolytic activity. A total of 144 strains were studied. Resistance to at least one of the antifungal compounds tested was found in 26.4% of the endophytic strains examined. Most of the strains were insensitive to fluconazole. Multiresistance was detected only in two strains of C. parapsilosis sensu stricto from tropical apples. Phospholipase production and proteolytic and hemolytic activities were significantly higher in endophytes from tropical fruits. Resistant and virulent strains of opportunistic yeasts can thus spread worldwide via purchased fruit, which can harm people with a weakened immune status and children whose immune systems are not yet fully developed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
References
Abi-Chacra EA, Souza LO, Cruz LP, Braga-Silva LA, Gonçalves DS, Sodre CL, Ribeiro MD, Seabra SH, Figueiredo-Carvalho MHG, Barbedo LS, Zancope-Oliveira RM, Ziccardi M, Santos AL (2013) Phenotypical properties associated with virulence from clinical isolates belonging to the Candida parapsilosis complex. FEMS Yeast Res 13(8):831–848. https://doi.org/10.1111/1567-1364.12092
Ahangarkani F, Badali H, Rezai MS, Shokohi T, Abtahian Z, Mahmoodi Nesheli H, Hossein Karami H, Emmanuel Roilides E, Tamaddoni A (2019) Candidemia due to Candida guilliermondii in an immuno-compromised infant: a case report and review of literature. Curr Med Mycol 5(1):32–36. https://doi.org/10.18502/cmm.5.1.535
Barbedo LS, Vaz C, Pais C, Figueiredo-Carvalho MHG, Muniz MDM, Zancope-Oliveira RM, Sampaio P (2015) Different scenarios for Candida parapsilosis fungaemia reveal high numbers of mixed C. parapsilosis and Candida orthopsilosis infections. J Med Microbiol 64:7–17. https://doi.org/10.1099/jmm.0.080655-0
Barry AL, Coyle MB, Thornsberry C, Gerlach EH, Hawkinson RW (1979) Methods of measuring zones of inhibition with the Bauer–Kirby disk susceptibility test. J Clin Microbiol 10(6):885–889
Bertini A, De Bernardis F, Hensgens LA, Sandini S, Senesi S, Tavanti A (2013) Comparison of Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis adhesive properties and pathogenicity. Int J Med Microbiol 303(2):98–103. https://doi.org/10.1016/j.ijmm.2012.12.006
Borman AM, Muller J, Walsh-Quantick J, Szekely A, Patterson Z, Palmer MD, Fraser M, Johnson EM (2020) MIC distributions for amphotericin B, fluconazole, itraconazole, voriconazole, flucytosine and anidulafungin and 35 uncommon pathogenic yeast species from the UK determined using the CLSI broth microdilution method. J Antimicrob Chemother 75(5):1194–1205. https://doi.org/10.1093/jac/dkz568
Branco J, Miranda IM, Rodrigues AG (2023) Candida parapsilosis virulence and antifungal resistance mechanisms: a comprehensive review of key determinants. J Fungi 9(1):80. https://doi.org/10.3390/jof9010080
Brilhante RSN, de Alencar LP, de Aguiar CR, Castelo DDSCM, Teixeira CEC, de Brito MR, de Oliveira MF (2013) Detection of Candida species resistant to azoles in the microbiota of rheas (Rhea americana): possible implications for human and animal health. J Med Microbiol 62(6):889–895. https://doi.org/10.1099/jmm.0.055566-0
Brilhante RSN, Alencar LP, Bandeira SP, Sales JA, Evangelista AJJ, Serpa R, Cordeiro RA, Pereira-Neto WA, Sidrim JJC, Castelo-Branco DSCM, Rocha MFG (2019) Exposure of Candida parapsilosis complex to agricultural azoles: an overview of the role of environmental determinants for the development of resistance. Sci Total Environ 650:1231–1238. https://doi.org/10.1016/j.scitotenv.2018.09.096
Buela L, Cuenca M, Sarmiento J, Peláez D, Mendoza AY, Cabrera EJ, Yarzábal LA (2022) Role of Guinea Pigs (Cavia porcellus) raised as livestock in Ecuadorian Andes as reservoirs of zoonotic yeasts. Animals 12(24):3449. https://doi.org/10.3390/ani12243449
Casadevall A (2005) Fungal virulence, vertebrate endothermy, and dinosaur extinction: is there a connection? Fungal Genet Biol 42:98–106. https://doi.org/10.1016/j.fgb.2004.11.008
Chaves A, Trilles L, Alves GM, Figueiredo-Carvalho M, Brito-Santos F, Coelho RA, Martins IS, Almeida-Paes R (2021) A case-series of bloodstream infections caused by the Meyerozyma guilliermondii species complex at a reference center of oncology in Brazil. Med Mycol 4:235–243. https://doi.org/10.1093/mmy/myaa044
Chen J, Tian S, Li F, Sun G, Yun K, Cheng S, Chu Y (2020) Clinical characteristics and outcomes of candidemia caused by Meyerozyma guilliermondii complex in cancer patients undergoing surgery. Mycopathologia 185:975–982. https://doi.org/10.1007/s11046-020-00485-2
Chen X-F, Zhang W, Fan X, Hou X, Liu X-Y, Huang J-J, Kang W, Zhang G, Zhang H, Yang W-H, Li Y-X, Wang J-W, Guo D-W, Sun Z-Y, Chen Z-J, Zou L-G, Du X-F, Pan Y-H, Li B, He H, Xu Y-C (2021) Antifungal susceptibility profiles and resistance mechanisms of clinical Diutina catenulata isolates with high MIC values. Front Cell Infect Microbiol 11:739496. https://doi.org/10.3389/fcimb.2021.739496
Ciurea CN, Kosovski IB, Mare AD, Toma F, Pintea-Simon IA, Man A (2020) Candida and candidiasis—opportunism versus pathogenicity: a review of the virulence traits. Microorganisms 8(6):857. https://doi.org/10.3390/microorganisms8060857
CLSI (2018) Epidemiological cut-off values for antifungal susceptibility testing. M59., 2nd edn. Clinical Laboratory Standards Institute, Wayne
CLSI (2022) Performance standards for antifungal susceptibility testing of yeasts, 3rd edn. Clinical and Laboratory Standards Institute, Wayne
Demirci-Duarte S, Arikan‐Akdagli S, Gülmez D (2021) Species distribution, azole resistance and related molecular mechanisms in invasive Candida parapsilosis complex isolates: increase in fluconazole resistance in 21 years. Mycoses 64(8):823–830. https://doi.org/10.1111/myc.13296
Doty SL (2013) Endophytic yeasts: biology and applications. In: Aroca R (ed) Symbiotic endophytes. Springer, Berlin, pp 335–343. https://doi.org/10.1007/978-3-642-39317-4_17
Dukare AS, Sangeeta P, Nambi VE, Gupta R, Sharma K, Vishwakarma RK (2018) Exploitation of microbial antagonists for the control of postharvest diseases of fruits: a review. Crit Rev Food Sci Nutr 16:1–16. https://doi.org/10.1080/10408398.2017.1417235
Dutra VR, Silva LF, Oliveira ANM, Beirigo EF, Arthur VM, Bernardes da Silva R, Silva MV, Fonseca FM, Silva-Vergara ML, Ferreira-Paim K (2020) Fatal case of fungemia by Wickerhamomyces anomalus in a pediatric patient diagnosed in a teaching hospital from Brazil. J Fungi 6(3):147. https://doi.org/10.3390/jof6030147
Fakhim H, Vaezi A, Javidnia J, Nasri E, Mahdi D, Diba K, Badali H (2020) Candida africana vulvovaginitis: prevalence and geographical distribution. J Mycol Médicale 30(3):100966. https://doi.org/10.1016/j.mycmed.2020.100966
Freimoser FM, Rueda-Mejia MP, Tilocca B, Migheli Q (2019) Biocontrol yeasts: mechanisms and applications. World J Microbiol Biotechnol 35:154. https://doi.org/10.1007/s11274-019-2728-4
Fu J, Ding Y, Wei B, Wang L, Xu S, Qin P (2017) Epidemiology of Candida albicans and non-C. Albicans of neonatal candidemia at a tertiary care hospital in western China. BMC Infect Dis 17:329. https://doi.org/10.1186/s12879-017-2423-8
Gai CS, Lacava PT, Maccheroni WJr, Glienke C, Araujo WL, Miller TA, Azevedo JL (2009) Diversity of endophytic yeasts from sweet orange and their localization by scanning electron microscopy. J Basic Microbiol 49:441–451. https://doi.org/10.1002/jobm.200800328
Ghasemi R, Lotfali E, Rezaei K, Madinehzad SA, Tafti MF, Aliabadi N, Kouhsari E, Fattahi M (2022) Meyerozyma guilliermondii species complex: review of current epidemiology, antifungal resistance, and mechanisms. Braz J Microbiol 53:1761–1779. https://doi.org/10.1007/s42770-022-00813-2
Gil-Alonso S, Quindos G, Eraso E, Jauregizar N (2019) Postantifungal effect of anidulafungin against Candida albicans, Candida dubliniensis, Candida africana, Candida parapsilosis, Candida metapsilosis and Candida orthopsilosis. Rev Esp Quimioter 32(2):183–188
Glushakova AM, Kachalkin AV (2017) Endophytic yeasts in Malus domestica and Pyrus communis fruits under anthropogenic impact. Microbiology 86:128–135. https://doi.org/10.1134/S0026261716060102
Glushakova AM, Kachalkin AV, Akhapkina IG (2017) The monitoring of sensitivity of natural strains and clinical isolates of yeast fungus to antimycotics. Klin Lab Diag 62:296–300. https://doi.org/10.18821/0869-2084-2017-62-5-296-299
Glushakova A, Kachalkin A, Rodionova E (2023) Hydrolytic enzyme production and susceptibility to antifungal compounds of opportunistic Candida parapsilosis strains isolated from Cucurbitaceae and Rosaceae fruits. Appl Microbiol 3:199–211
Gongora-Echeverria VR, Martin-Laurent F, Quintal-Franco C, Lorenzo-Flores A, Giácoman-Vallejos G, Ponce-Caballero C (2019) Dissipation and adsorption of 2,4-D, atrazine, diazinon, and glyphosate in an agricultural soil from Yucatan State, Mexico. Water Air Soil Pollut 230:1e15. https://doi.org/10.1007/s11270-019-4177-y
GŘler NC, Tosun İLKNUR, Aydin FARUK (2017) The identification of Meyerozyma guilliermondii from blood cultures and surveillance samples in a university hospital in Northeast Turkey: a ten-year survey. J Mycol MÚdicale 27(4):506–513. https://doi.org/10.1016/j.mycmed.2017.07.007
Hirayama T, Miyazaki T, Yamagishi Y, Mikamo H, Ueda T, Nakajima K, Mukae H (2018) Clinical and microbiological characteristics of Candida guilliermondii and Candida fermentati. Antimicrob Agents Chemother 62(6):e02528–e02517. https://doi.org/10.1128/AAC.02528-17
Israel S, Amit S, Israel A, Livneh A, Nir-Paz R, Korem M (2019) The epidemiology and susceptibility of Candidemia in Jerusalem, Israel. Front Cell Infect Microbiol 9:352. https://doi.org/10.3389/fcimb.2019.00352
Kachalkin AV, Glushakova AM, Venzhik AS (2021) Presence of clinically significant endophytic yeasts in agricultural crops: monitoring and ecological safety assessment. IOP Conf Ser 723:042005. https://doi.org/10.1088/1755-1315/723/4/042005
Ksiezopolska E, Gabaldon T (2018) Evolutionary emergence of drug resistance in Candida opportunistic pathogens. Genes 9(9):461. https://doi.org/10.3390/genes9090461
Ling L, Tu Y, Ma W, Feng S, Yang C, Zhao Y, Wang N, Li Z, Lu L, Zhan J (2020) A potentially important resource: endophytic yeasts. World J Microbiol Biotechnol 36:110. https://doi.org/10.1007/s11274-020-02889-0
Luo G, Samaranayake LP, Yau JY (2001) Candida species exhibit differential in vitro hemolytic activities. J Clin Microbiol 39:2971–2974. https://doi.org/10.1128/JCM.39.8.2971-2974.2001
Magnoli K, Carranza CS, Aluffi ME, Benito N, Magnoli CE, Barberis CL (2022) Survey of organochlorine-tolerant culturable mycota from contaminated soils, and 2, 4-D removal ability of Penicillium species in synthetic wastewater. Fungal Biol 127(1–2):891–899. https://doi.org/10.1016/j.funbio.2022.11.003
Mahboob N, Iqbal H, Ahmed M, Magnet MMH, Mamun KZ (2019) Disk diffusion method in enriched Mueller Hinton agar for determining susceptibility of Candida isolates from various clinical specimens. J Dhaka Med Coll 28(1):28–33. https://doi.org/10.3329/jdmc.v28i1.45753
McCarty TP, Pappas PG (2016) Invasive candidiasis. Infect Dis Clin North Am 30:103–124. https://doi.org/10.1038/nrdp.2018.26
Mellinghoff SC, Cornely OA, Jung N (2018) Essentials in Candida bloodstream infection. Infection 46:897–899. https://doi.org/10.1007/s15010-018-1218-1
Mesini A, Mikulska M, Giacobbe DR, Del Puente F, Gandolfo N, Codda G, Orsi A, Tassinari F, Beltramini S, Marchese A (2020) Changing epidemiology of candidaemia: increase in fluconazole-resistant Candida parapsilosis. Mycoses 63:361–368. https://doi.org/10.1111/myc.13050
Methot P-O, Alizon S (2014) What is a pathogen? Toward a process view of host-parasite interactions. Virulence 5:775–785. https://doi.org/10.4161/21505594.2014.960726
Monod M, Capoccia S, Lechenne B, Zaugg C, Holdom M, Jousson O (2002) Secreted proteases from pathogenic fungi. Int J Med Microbiol 292(5–6):405–419. https://doi.org/10.1078/1438-4221-00223
Pappas PG, Lionakis MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ (2018) Invasive candidiasis. Nat Rev Dis Primers 4:18026. https://doi.org/10.1038/nrdp.2018.26
Pfaller MA (2012) Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med 125:3–13. https://doi.org/10.1016/j.amjmed.2011.11.001
Pfaller MA, Diekema DJ (2012) Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standards Institute broth microdilution methods, 2010 to 2012. J Clin Microbiol 50:2846–2856. https://doi.org/10.1128/JCM.00937-12
Pfaller MA, Diekema DJ, Mendez M, Kibbler C, Erzsebet P, Chang SC, Gibbs DL, Newell VA, The global antifungal surveillance group (2006) Candida guilliermondii, an opportunistic fungal pathogen with decreased susceptibility to fluconazole: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program. J Clin Microbiol 44(10):3551–3556. https://doi.org/10.1128/JCM.00865-06
Pfaller MA, Diekema DJ, Turnidge JD, Castanheira M, Jones RN (2019) Twenty years of the SENTRY antifungal surveillance program: results for Candida species from 1997–2016. Open Forum Infect Dis 6:79–94. https://doi.org/10.1093/ofid/ofy358
Price MF, Wilkinson ID, Gentry LO (1982) Plate method for detection of phospholipase activity in Candida albicans. Sabouraudia 20:7–14
Prigitano A, Blasi E, Calabrò M, Cavanna C, Cornetta M, Farina C, Grancini A, Innocenti P, Lo Cascio G, Nicola L, Trovato L, Cogliati M, Esposto MC, Tortorano AM, Romanò L and on behalf of the FiCoV study group (2023) Yeast bloodstream infections in the COVID-19 patient: a multicenter italian study (FiCoV Study). J Fungi 9:277. https://doi.org/10.3390/jof9020277
Pristov KE, Ghannoum MA (2019) Resistance of Candida to azoles and echinocandins worldwide. Clin Microbiol Infect 25:792–798. https://doi.org/10.1016/j.cmi.2019.03.028
Rhimi W, Aneke CI, Annoscia G, Camarda A, Mosca A, Cantacessi C, Domenico Otranto D, Cafarchia C (2021) Virulence and in vitro antifungal susceptibility of Candida albicans and Candida catenulata from laying hens. Int Microbiol 24(1):57–63. https://doi.org/10.1007/s10123-020-00141-1
Rocha MF, Alencar LP, Paiva MA, Melo LM, Bandeira SP, Ponte YB, Sales JA, Guedes GM, Castelo-Branco DS, Bandeira TJ, Cordeiro RA, Pereira-Neto WA, Brandine GS, Moreira JL, Sidrim JJ, Brilhante RS (2016) Cross-resistance to fluconazole induced by exposure to the agricultural azole tetraconazole: an environmental resistance school? Mycoses 59:281–290. https://doi.org/10.1111/myc.12457
Rodrigues DKB, Bonfietti LX, Garcia RA, Araujo MR, Rodrigues JS, Gimenes VMF, Melhem MSC (2021) Antifungal susceptibility profile of Candida clinical isolates from 22 hospitals of São Paulo State, Brazil. Braz J Med Biol Res 54(9):e10928. https://doi.org/10.1590/1414-431X2020e10928
Rossoni RD, Barbosa JO, Vilela SFG, dos Santos JD, Jorge AOC, Junqueira JC (2013) Correlation of phospholipase and proteinase production of Candida with in vivo pathogenicity in Galleria mellonella. Braz J Oral Sci 12(3):199–204
Rüchel J, Tegeler R, Trost MA (1982) Comparison of secretory proteinases from different strains of Candida albicans. Sabouraudia 20:233–244
Sanguinetti M, Posteraro B, Lass-Florl C (2015) Antifungal drug resistance among Candida species: mechanisms and clinical impact. Mycoses 58:2–13. https://doi.org/10.1111/myc.12330
Schoch CL, Seifert KA, Huhndorf S, Robert V, Spouge JL, Levesque CA, White MM (2012) Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. Proc Natl Acad Sci 109(16):6241–6246. https://doi.org/10.1073/pnas.1117018109
Subramanya SH, Baral BP, Sharan NK, Nayak N, Metok Y, Sathian B, Gokhale S (2017) Antifungal susceptibility and phenotypic virulence markers of Candida species isolated from Nepal. BMC Res Notes 10(1):543. https://doi.org/10.1186/s13104-017-2852-x
van Asbeck EC, Huang YC, Markham AN, Clemons KV, Stevens DA (2007) Candida parapsilosis fungemia in neonates: genotyping results suggest healthcare workers hands as source, and review of published studies. Mycopathologia 164:287–293. https://doi.org/10.1007/s11046-007-9054-3
Vanreppelen G, Wuyts J, Van Dijck P, Vandecruys P (2023) Sources of antifungal drugs. J Fungi 9:171. https://doi.org/10.3390/jof9020171
Vu D, Groenewald M, Szöke S, Cardinali G, Eberhardt U, Stielow B, de Vries M, Verkleij GJM, Crous PW, Boekhout T, Robert V (2016) DNA barcoding analysis of more than 9 000 yeast isolates contributes to quantitative thresholds for yeast species and genera delimitation. Stud Mycol 85(1):91–105
Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39:309–317. https://doi.org/10.1086/421946
Yadav A, Jain K, Wang Y, Pawar K, Kaur H, Sharma KK, Tripathy V, Singh A, Xu J, Chowdhary A (2022) Candida auris on apples: diversity and clinical significance. mBio 13:00518–00522. https://doi.org/10.1128/mbio.00518-22
Yamin D, Akanmu MH, Al Mutair A, Alhumaid S, Rabaan AA, Hajissa K (2022) Global prevalence of antifungal-resistant Candida parapsilosis: a systematic review and meta-analysis. Trop Med Infect Dis 7(8):188
Yılmaz Semerci S, Demirel G, ve Taştekin A (2017) Wickerhamomyces anomalus blood stream infection in a term newborn with pneumonia. Turk J Pediatr 59(3):349–351. https://doi.org/10.24953/turkjped.2017.03.021
Zhang L, Xiao M, Arastehfar A, Ilkit M, Zou J, Deng Y, Xu Y, Liao W, Zhao J, Fang W, Pan W (2021) Investigation of the emerging nosocomial Wickerhamomyces anomalus infections at a chinese tertiary teaching hospital and a systemic review: clinical manifestations, risk factors, treatment, outcomes, and anti-fungal susceptibility. Front Microbiol 12:744502
Acknowledgements
The study was carried out on the scientific equipment of the Collective Usage Center “I.I. Mechnikov NIIVS”, Moscow, Russia, with the financial support of the project by the Russian Federation represented by the Ministry of Science of Russia, Agreement No. 075-15-2021-676 dated 28.07.2021.
Funding
This research was funded by the Russian Ministry of Science and Higher Education, Grant Agreement No. 075-15-2021-1396.
Author information
Authors and Affiliations
Contributions
AG and AK wrote the main manuscript text, prepared figures and tables and ER made formal analysis. All authors reviewed the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study.
Ethical approval
The study was approved by the Ethics Committee of Lomonosov Moscow State University.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Glushakova, A., Kachalkin, A. & Rodionova, E. The role of fruits as reservoirs for resistant and virulent strains of opportunistic yeasts. World J Microbiol Biotechnol 39, 313 (2023). https://doi.org/10.1007/s11274-023-03758-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11274-023-03758-2