禽光滑念珠菌研究进展

doi:10.16431/j.cnki.1671-7236.2021.03.025

摘要/Abstract

摘要： 光滑念珠菌逐渐发展成为禽念珠菌属第二大致病菌，该菌通常是口腔、食道、胃肠道的正常菌群，当机体免疫力下降时即表现出对宿主的致病性，菌株一旦进入血液便会扩散到全身，造成系统性念珠菌病。光滑念珠菌主要感染鸡和鸽，临床中以禽食欲减退、消瘦、发育迟缓、羽毛松散和精神沉郁为主要症状，剖检可见嗉囔黏膜表面形成白色假膜或白色圆形隆起溃疡，形似地毯状病变，俗称念珠菌症。光滑念珠菌侵染过程中以酵母形态存在，未见其菌丝形态，入侵时通过形成生物膜来逃避医学灭菌、消毒作用，利用黏附素家族形成的黏附素吸附入侵宿主，依靠水解蛋白酶等相关毒力因子破坏宿主细胞，从而表现出致病性。动物机体以巨噬细胞吞噬及氧化应激反应来抵抗光滑念珠菌的侵染，该菌则通过过氧化氢酶和超氧化物歧化酶两种解毒酶的表达及抗氧化剂谷胱甘肽和硫氧还蛋白的产生来解毒活性氧化物，从而在机体免疫攻击中幸存。为了应对光滑念珠菌感染造成的经济损失，长时间大规模的使用抗真菌药物导致光滑念珠菌耐药性不断增强，对一线抗真菌药物尤其是唑类药表现出高耐药性。研究者逐渐倾向于利用天然物质提取物来解决光滑念珠菌耐药性问题。现从光滑念珠菌病原学、毒力因子及致病性、流行病学、抗菌药物、检测技术等方面进行综述，以期为研制有效抗菌药物防治念珠菌病提供理论依据。

关键词: 光滑念珠菌; 病原学; 毒力因子及致病性; 流行病学; 抗菌药物

Abstract: Candida glabrata had gradually developed into the second largest pathogen in poultry Candida,which was usually a normal flora in the oral cavity,esophagus and gastrointestinal tract.When the immunity of the body decreased,it showed pathogenicity to the host,and with the increase of infection,once the strain entered the blood,it spread to the whole body,resulting in systemic candidiasis.Candida glabrata mainly infected chickens and pigeons.In clinic,the main symptoms was loss of appetite and emaciation,growth retardation,loose feathers and mental depression.Autopsy showed that white pseudomembrane or white round uplift ulcer was formed on the surface of crop mucosa,which was similar to carpet-like disease,commonly known as candidiasis.Candida glabrata existed in the form of yeast in the process of infection,and its mycelium morphology was not seen.During the invasion,Candida glabrata formed a biofilm to escape medical sterilization and disinfection,and used adhesin formed by adhesin family to absorb and invade the host.It could destroy host cells by hydrolyzing protease and other virulence factors,thus showing pathogenicity.The animal body used macrophage phagocytosis and oxidative stress to resist the infection of Candida glabrata.The bacteria detoxified actived oxides through the expression of catalase and superoxide dismutase detoxifying enzymes and the production of antioxidants glutathione and thioredoxin,thus survived immune attacks.In order to cope with the economic loss caused by Candida glabrata infection,the long-term and large-scale used of antifungal drugs led to the increasing of drug resistance,and Candida glabrata showed high drug resistance to first-line antifungal drugs,especially azoles.Researchers were increasingly inclined to use natural extracts to solve the problem of drug resistance of Candida glabrata.This paper reviewed the etiology,virulence factors and pathogenicity,epidemiology,antibiotics and detection techniques of Candida glabrata,in order to provide a theoretical basis for the development of effective antibiotics and more effective prevention and treatment of candidiasis in the future.

Key words: Candida glabrata; etiology; virulence factors and pathogenicity; epidemiology; antimicrobials

中图分类号:

S855.4

张双, 郭禹, 薛文慧, 赵千惠, 霍书英. 禽光滑念珠菌研究进展[J]. 中国畜牧兽医, 2021, 48(3): 1013-1019.

ZHANG Shuang, GUO Yu, XUE Wenhui, ZHAO Qianhui, HUO Shuying. Research Progress on Poultry Candida glabrata[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(3): 1013-1019.

参考文献

[1] ORTEGA-RIVEROS M,DE-LA-PINTA I,MARCOS-ARIAS C,et al.Usefulness of the non-conventional Caenorhabditis elegans model to assess Candida virulence[J].Mycopathologia,2017,182(9-10):785-795.
[2] 阎力君,吕欣彧,张多,等.黄连解毒汤有效成分的提取及其对体内白色念珠菌的清除作用[J].中国畜牧兽医,2019,46(11):3414-3421. YAN L J,LYU X Y,ZHANG D,et al.Extraction of effective fraction of Huanglian Jiedu decoction and its scavenging effect on Candida albicans in vivo[J].China Animal Husbandry & Veterinary Medicine,2019,46(11):3414-3421.(in Chinese)
[3] FAKHIM H,VAEZI A,DANNAOUI E,et al.Comparative virulence of Candida auris with Candida haemulonii,Candida glabrata and Candida albicans in a murine model[J].Mycoses,2018,61(6):377-382.
[4] FATAHINIA M,HALVAEEZADEH M,REZAEI-MATEHKOLAEI A.Comparison of enzymatic activities in different Candida species isolated from women with vulvovaginitis[J].Journal De Mycologie Medicale,2017,27(2):188-194.
[5] RICETO É B,MENEZES RDE P,PENATTI M P,et al.Enzymatic and hemolytic activity in different Candida species[J].Revista Iberoamericana De Micologia,2015,32(2):79-82.
[6] RASHEED M,BATTU A,KAUR R.Aspartyl proteases in Candida glabrata are required for suppression of the host innate immune response[J].Journal of Biological Chemistry,2018,293(17):6410-6433.
[7] KUCHARKOV S,NEIRINCK B,SHARMA N,et al.In vivo Candida glabrata biofilm development on foreign bodies in a rat subcutaneous model[J].Journal of Antimicrobial Chemotherapy,2015,70(3):846-856.
[8] TATI S,DAVIDOW P,MCCALL A,et al.Candida glabrata binding to Candida albicans hyphae enables its development in oropharyngeal candidiasis[J].PLoS Pathogens,2016,12(3):e1005522.
[9] CSANK C,HAYNES K.Candida glabrata displays pseudohyphal growth[J].FEMS Microbiology Letters,2000,189(1):115-120.
[10] SASANI E,KHODAVAISY S,AFSHARI S.et al.Pseudohyphae formation in Candida glabrata due to CO₂ exposure[J].Current Medical Mycology,2016,2(4):49-52.
[11] SASCHA B,KATJA S,DANIEL F,et al.One small step for a yeast-microevolution within macrophages renders Candida glabrata hypervirulent due to a single point mutation[J].PLoS Pathogens,2014,10(10):e1004478.
[12] VITENSHTEIN A,CHARPAK-AMIKAM Y,YAMIN R,et al.NK cell recognition of Candida glabrata through binding of NKp46 and NCR1 to fungal ligands Epa1,Epa6,and Epa7[J].Cell Host & Microbe,2016,20(4):527-534.
[13] TIAN Y,ZHUANG Y,CHEN Z,et al.A gain-of-function mutation in PDR1 of Candida glabrata decreases EPA1 expression and attenuates adherence to epithelial cells through enhancing recruitment of the mediator subunit Gal11A[J].Microbiological Research,2020,239(9):126519-126532.
[14] SHANG J Y,CHANG Y L,YING L C.Deletion of ADA2 increases antifungal drug susceptibility and virulence in Candida glabrata[J].Antimicrob Agents Chemother,2018,62(3):e01924.
[15] SEIDER K,BRUNKE S,SCHILD L,et al.The facultative intracellular pathogen Candida glabrata subverts macrophage cytokine production and phagolysosome maturation[J].Journal of Immunology,2011,187(6):3072-3086.
[16] SUI X,YAN L,JIANG Y Y.The vaccines and antibodies associated with Als3p for treatment of Candida albicans infections[J].Vaccine,2017,35(43):5786-5793.
[17] MEDRANO-DIAZ C L,VEGA-GONZALEZ A,RUIZ-BACA E,et al.Moonlighting proteins induce protection in a mouse model against Candida species[J].Microbial Pathogenesis,2018,3(124):21-29.
[18] SHARMA V,PURUSHOTHAM R,KAUR R.The phosphoinositide 3-kinase regulates retrograde trafficking of the iron permease CgFtr1 and iron homeostasis in Candida glabrata[J].The Journal of Biological Chemistry,2016,291(47):24715-24734.
[19] SANTOS R,COSTA C,MIL-HOMENS D,et al.The multidrug resistance transporters CgTpo1_1 and CgTpo1_2 play a role in virulence and biofilm formation in the human pathogen Candida glabrata[J].Cellular Microbiology,2017,19(5):e12686.
[20] CHEN S M,SHEN H,ZHANG T,et al.Dectin-1 plays an important role in host defense against systemic Candida glabrata infection[J].Virulence,2017,8(8):1643-1656.
[21] ROSSONI R D,DE BARROS P P,LOPES L,et al.Effects of surface pre-reacted glass-ionomer (S-PRG) eluate on Candida spp.:Antifungal activity,anti-biofilm properties,and protective effects on Galleria mellonella against C.albicans infection[J].Biofouling,2019,35(9):997-1006.
[22] SENEVIRATNE C J,SILVA W J,JIN L J.Architectural analysis,viability assessment and growth kinetics of Candida albicans and Candida glabrata biofilms[J].Archives of Oral Biology,2009,54(11):1052-1060.
[23] SEIDER K,GERWIEN F,KASPER L,et al.Immune evasion,stress resistance and efficient nutrient acquisition are crucial for intracellular survival of Candida glabrata within macrophages[J].Eukaryotic Cell,2013,13(1):170-183.
[24] GUTIERREZ-ESCOBEDO G,HERNANDEZ-CARREON O,MORALES-ROJANO B,et al.Candida glabrata peroxiredoxins,Tsa1 and Tsa2,and sulfiredoxin,Srx1,protect against oxidative damage and are necessary for virulence[J].Fungal Genetics and Biology,2020,135(7):103287-103312.
[25] ABASSI S,EMTIAZI G,HOSSEINI-ABARI A,et al.Chitooligosaccharides and thermostable chitinase against vulvovaginal candidiasis and saprophyte fungi:LC mass studies of shrimp shell fermentation by Bacillus altitudinis[J].Current Microbiology,2020,77(1):40-48.
[26] CANELA H M S,CARDOSO B,VITALI L H,et al.Prevalence,virulence factors and antifungal susceptibility of Candida spp.isolated from bloodstream infections in a tertiary care hospital in Brazil[J].Mycoses,2018,61(1):11-21.
[27] AL-YASIRI M H,NORMAND A C,LOLLIVIER C,et al.Opportunistic fungal pathogen Candida glabrata circulates between humans and yellow-legged gulls[J].Scientific Reports,2016,6(2):36157-36164.
[28] CAFARCHIA C,IATTA R,DANESI P,et al.Yeasts isolated from cloacal swabs,feces,and eggs of laying hens[J].Medical Mycology,2019,57(3):340-345.
[29] PARIN U,ERBAS G,KIRKAN S,et al.Detection of Candida species by nested PCR method in one-humped camels (Camelus dromedarius)[J].Tropical Animal Health and Production,2018,50(2):421-425.
[30] BORDALLO-CARDONA M A,ESCRIBANO P,MARCOS-ZAMBRANO L J,et al.Low and constant micafungin concentrations may be sufficient to lead to resistance mutations in FKS2 gene of Candida glabrata[J].Medical Mycology,2018,56(7):903-906.
[31] KOUNATIDIS I,AMES L,MISTRY R,et al.A host-pathogen interaction screen identifies ada2 as a mediator of Candida glabrata defenses against reactive oxygen species[J].G3 Genesgenetics,2018,8(5):1637-1647.
[32] BOUKLAS T,ALONSO-CRISOSTOMO L,SZEKELY T,et al.Generational distribution of a Candida glabrata population:Resilient old cells prevail,while younger cells dominate in the vulnerable host[J].PLoS Pathogens,2017,13(5):e1006355.
[33] HEALEY K R,ZHAO Y,PEREZ W B,et al.Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance[J].Nature Communications,2016,7(5):11128-11138.
[34] LEPAK A J,ZHAO M,VANSCOY B,et al.Pharmacodynamics of a long-acting echinocandin,CD101,in a neutropenic invasive-candidiasis murine model using an extended-interval dosing design[J].Antimicrobial Agents and Chemotherapy,2018,62(2):e02154-17.
[35] PAGNIEZ F,LEBOUVIER N,NA Y M,et al.Biological exploration of a novel 1,2,4-triazole-indole hybrid molecule as antifungal agent[J].Journal of Enzyme Inhibition and Medicinal Chemistry,2020,35(1):398-403.
[36] PONTES DE SOUSA I,FERREIRA A G,MILLER CROTTI A E,et al.New antifungal ent-labdane diterpenes against Candida glabrata produced by microbial transformation of ent-polyalthic acid[J].Bioorganic Chemistry,2020,95(5):103560-103568.
[37] GRISIN T,BORIES C,LOISEAU P M,et al.Cyclodextrin-mediated self-associating chitosan micro-platelets act as a drug booster against Candida glabrata mucosal infection in immunocompetent mice[J].International Journal of Pharmaceutics,2017,519(1-2):381-389.
[38] APARNA V,MELGE A R,RAJAN V K,et al.Carboxymethylated-carrageenan conjugated ampho-tericin B loaded gelatin nanoparticles for treating intracellular Candida glabrata infections[J].Interna-tional Journal of Biological Macromolecules,2018,110(2):140-149.
[39] LILLY E A,IKEH M,NASH E E,et al.Immune protection against lethal fungal-bacterial intra-abdominal infections[J].mBio,2018,9(1):72-80.
[40] RAMIREZ-CARRETO S,JIMENEZ-VARGAS J M,RIVAS-SANTIAGO B,et al.Peptides from the scorpion Vaejovis punctatus with broad antimicrobial activity[J].Peptides,2015,73(3):51-59.
[41] AL-ASMARI A K,ALAMRI M A,ALMASOUDI A S,et al.Evaluation of the in vitro antimicrobial activity of selected Saudi scorpion venoms tested against multidrug-resistant micro-organisms[J].Journal of Global Antimicrobial Resistance,2017,10(4):14-18.
[42] ANAND J,RAI N.Anticandidal synergistic activity of green tea catechins,antimycotics and copper sulphate as a mean of combinational drug therapy against candidiasis[J].Journal De Mycologie Medicale,2017,27(1):33-45.
[43] YAMANE E S,BIZERRA F C,OLIVEIRA E B,et al.Unraveling the antifungal activity of a South American rattlesnake toxin crotamine[J].Biochimie,2013,95(2):231-240.
[44] DE FREITAS A L D,KAPLUM V,ROSSI D C P,et al.Proanthocyanidin polymeric tannins from Stryphnodendron adstringens are effective against Candida spp.isolates and for vaginal candidiasis treatment[J].Journal of Ethnopharmacology,2018,216(5):184-190.
[45] ADAM M S S,ELSAWY H.Biological potential of oxo-vanadium salicylediene amino-acid complexes as cytotoxic,antimicrobial,antioxidant and DNA interaction[J].Journal of Photochemistry and Photobiology Biology,2018,184(6):34-43.
[46] OLIVEIRA W N,AMARAL-MACHADO L,ALENCAR E N,et al.Getting the jump on the development of bullfrog oil microemulsions:A nanocarrier for amphotericin B intended for antifungal treatment[J].AAPS PharmSciTech,2018,19(6):2585-2597.
[47] CASTRO M R,VICTORIA F N,OLIVEIRA D H,et al.Essential oil of psidium cattleianum leaves:Antioxidant and antifungal activity[J].Pharma-ceutical Biology,2015,53(2):242-250.
[48] MARTINS C V B,SILVA D L D,NERES A T M,et al.Curcumin as a promising antifungal of clinical interest[J].Journal of Antimicrobial Chemotherapy,2009,63(2):337-339.
[49] NANI B D,SARDI J C O,LAZARINI J G,et al.Anti-inflammatory and anti-Candida effects of Brazilian organic propolis,a promising source of bioactive molecules and functional food[J].Journal of Agricultural and Food Chemistry,2020,68(10):2861-2871.
[50] LAU A,HALLIDAY C,CHEN S,et al.Comparison of whole blood,serum and plasma for early detection of candidemia by multiplex-tandem PCR[J].Journal of Clinical Microbiology,2010,48(3):811-816.
[51] TAIRA C L,OKAY T S,DELGADO A F,et al.A multiplex nested PCR for the detection and identification of Candida species in blood samples of critically ill paediatric patients[J].BMC Infectious Diseases,2014,14(8):406-413.
[52] 刘利强,宋阔阔,李慧芳,等.光滑念珠菌SYBR Green荧光定量PCR检测方法的建立及应用[J].中国兽医科学,2019,49(5):604-610. LIU L Q,SONG K K,LI H F,et al.Establishment and application of SYBR Green fluorescent quantitative PCR detecting Candida glabrata[J].Chinese Veterinary Science,2019,49(5):604-610.(in Chinese)
[53] 石星亮,余一海,陈静,等.白色念珠菌的快速检测技术开发[J].检验医学与临床,2020,17(9):1189-1191. SHI X L,YU Y H,CHEN J,et al.Development of rapid testing technology for Candida albicans[J].Labo-ratory Medicine and Clinic,2020,17(9):1189-1191.(in Chinese)