Publications by authors named "Guanghua Huang"

69 Publications

infections in China.

Virulence 2022 12;13(1):589-591

Shanghai Institute of Infectious Disease and Biosecurity, Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21505594.2022.2054120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037403PMC
December 2022

suppresses filamentous growth of through secreting mutanocyclin, an unacylated tetramic acid.

Virulence 2022 12;13(1):542-557

Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.

Fungi and bacteria often co-exist and physically or chemically interact with each other in their natural niches. This inter-kingdom species interaction is exemplified by the gram-positive bacterial pathogen and opportunistic fungal pathogen , which co-exist in the human mouth. It has been demonstrated that the dynamic interaction between these two species plays a critical role in their virulence and biofilm development. In this study, we discovered that represses filamentous development and virulence in through secreting a secondary metabolite, mutanocyclin (a tetramic acid). Mutanocyclin functions by regulating the PKA catabolic subunit Tpk2 and its preferential binding target Sfl1. Inactivation of Tpk2 in results in an increased sensitivity to mutanocyclin, whereas overexpression of Tpk2 leads to an increased resistance. Dysfunction of and its downstream target genes overrides the hyphal growth defect caused by mutanocyclin. Further investigation demonstrates that three glycosylphosphatidylinositol (GPI)-anchored proteins (Spr1, Hyr4, and Iff8), associated with cell wall biogenesis and remodeling, and a set of filamentous regulators also contribute to the mutanocyclin response. We propose that both transcriptional regulation and cell wall composition contribute to mutanocyclin-mediated filamentous inhibition. This repressive effect of mutanocyclin could function as a natural regulator of filamentous development in .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21505594.2022.2046952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942415PMC
December 2022

Higher cystatin C level increases the risk of delayed cerebral ischemia after endovascular treatment of aneurysmal subarachnoid hemorrhage: a case-control study.

Neurosurg Rev 2022 Mar 5. Epub 2022 Mar 5.

Department of Neurosurgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, China.

Cystatin C (CysC) has been found to be associated with hemorrhagic and ischemic stroke in many studies. However, the association between CysC level and the risk of delayed cerebral ischemia after endovascular treatment of aneurysmal subarachnoid hemorrhage has been reported rarely. Our study was proposed to explore this association. Consecutive patients from June 2015 to February 2021 in this single-center retrospective study were selected. Univariate and multivariate analyses were used to identify potential prognostic risk factors for delayed cerebral ischemia, and the stability of the association was demonstrated by several statistical methods, such as subgroup analysis, interaction testing, generalized linear models, and propensity score matching. A total of 424 patients were included in the analysis. Cystatin C was independently associated with delayed cerebral ischemia. The independent effects of CysC on delayed cerebral ischemia were shown in generalized linear models with a logit link, and the results were relatively stable in crude, partial, and full models with ORs (95% CIs) for delayed cerebral ischemia. Subgroup analysis showed no significant subgroup differences in the effect of CysC on delayed cerebral ischemia. There was also no interaction effect between CysC and other confounders. Patients in the high CysC group had a higher risk of delayed cerebral ischemia than those in the low CysC group before and after propensity score matching. CysC level could be an independent predictor for the risk of delayed cerebral ischemia after endovascular treatment of aneurysmal subarachnoid hemorrhage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10143-022-01765-9DOI Listing
March 2022

External validation of five predictive models for postoperative cardiopulmonary morbidity in a Chinese population receiving lung resection.

PeerJ 2022 9;10:e12936. Epub 2022 Feb 9.

Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: No postoperative cardiopulmonary morbidity models have been developed or validated in Chinese patients with lung resection. This study aims to externally validate five predictive models, including Eurolung models, the Brunelli model and the Age-adjusted Charlson Comorbidity Index, in a Chinese population.

Methods: Patients with lung cancer who underwent anatomic lung resection between 2018/09/01 and 2019/08/31 in our center were involved. Model discrimination was assessed by the area under the receiver operating characteristic curve. Model calibration was evaluated by the Hosmer-Lemeshow test. Calibration curves were plotted. Specificity, sensitivity, negative predictive value, positive predictive value and accuracy were calculated. Model updating was achieved by re-estimating the intercept and/or the slope of the linear predictor and re-estimating all coefficients.

Results: Among 1085 patients, 91 patients had postoperative cardiopulmonary complications defined by the European Society of Thoracic Surgeons. For original models, only parsimonious Eurolung1 had acceptable discrimination (area under the receiver operating characteristic curve = 0.688, 95% confidence interval 0.630-0.745) and calibration ( = 0.23 > 0.05) abilities simultaneously. Its sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 0.700, 0.649, 0.153, 0.960 and 0.653, respectively. In the secondary analysis, increased pleural effusion ( = 94), which was nonchylous and nonpurulent, was labeled as a kind of postoperative complication. The area under the receiver operating characteristic curve of the models increased slightly, but all models were miscalibrated. The original Eurolung1 model had the highest discrimination ability but poor calibration, and thus it was updated by three methods. After model updating, new models showed good calibration and small improvements in discrimination. The discrimination ability was still merely acceptable.

Conclusions: Overall, none of the models performed well on postoperative cardiopulmonary morbidity prediction in this Chinese population. The original parsimonious Eurolung1 and the updated Eurolung1 were the best-performing models on morbidity prediction, but their discrimination ability only achieved an acceptable level. A multicenter study with more relevant variables and sophisticated statistical methods is warranted to develop new models among Chinese patients in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.12936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8840067PMC
February 2022

A case of candidemia in Xiamen, China, and a comparative analysis of clinical isolates in China.

Mycology 2022 31;13(1):68-75. Epub 2021 Oct 31.

Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

The recently emerged fungal pathogen  often displays resistance to one or more antifungal drugs. Its infections have been identified in at least 40 countries on six continents to date. Here we report a case of  candidemia in a patient in Xiamen, a city in south China. We also review currently reported cases of infection in China and compare the genetic and biological features of strains isolated from this country. Our phylogenetic analysis indicates that there are at least two genetic clades present in China (the South African clade and the south Asian clade) that display opposite mating type loci (one is   and the other is α). We also found that there are several distinct features among the clinical isolates studied, including the expression of virulence factors, antifungal susceptibilities, and cellular morphologies, and that these features could be associated with the mating-type of the isolate. For example,    isolates generally secreted higher levels of secreted aspartyl proteases (Saps) at ambient environmental temperatures. Taken together, this study demonstrates that  clinical isolates from China exhibit diversity in both biological and genetic features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21501203.2021.1994479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8856026PMC
October 2021

Effects of lobectomy in stage II/IIIA second primary lung cancer patients with prior non-small cell lung cancer: a SEER-based study.

Gen Thorac Cardiovasc Surg 2022 May 3;70(5):463-471. Epub 2022 Feb 3.

Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan, Beijing, 100730, China.

Objective: Our study aimed to reveal the prognostic factors of second primary lung cancer and explore the optimal surgical procedure for Stage II/IIIA second primary lung cancer patients with prior non-small cell lung cancer.

Methods: Patients with Stage II/IIIA second primary lung cancer were collected from the Surveillance, Epidemiology and End Results database from 2004 to 2016. Lasso regression, along with univariate and multivariate Cox regression, was used to screen prognostic factors. The propensity score matching was used to minimize baseline differences, and restricted mean survival time was used to compare overall survival and cancer-specific survival of different groups.

Results: A total of 579 patients were enrolled in the study. After data was screened by lasso regression and univariate Cox regression, multivariate Cox regression revealed that age, sex, race, tumor size of initial primary lung cancer, tumor size, histological grade, T stage, N stage and surgical procedure of second primary lung cancer were independent prognostic factors. Further analysis showed that surgery, especially lobectomy, provided better survival in Stage II/IIIA second primary lung cancer.

Conclusions: Our study identified nine independent prognostic factors of Stage II/IIIA second primary lung cancer. Surgery can provide a better prognosis, and lobectomy might be the optimal surgical procedure for these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11748-021-01759-2DOI Listing
May 2022

Candida albicans MTLa2 regulates the mating response through both the a-factor and α-factor sensing pathways.

Fungal Genet Biol 2022 04 10;159:103664. Epub 2022 Jan 10.

Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. Electronic address:

The diploid fungal pathogen Candida albicans has three configurations at the mating type locus (MTL): heterozygous (a/α) and homozygous (a/a or α/α). C. albicans MTL locus encodes four transcriptional regulators (MTLa1, a2, α1, and α2). The conserved a1/α2 heterodimer controls not only mating competency but also white-opaque heritable phenotypic switching. However, the regulatory roles of MTLa2 and α1 are more complex and remain to be investigated. MTLa/a cells often express a cell type-specific genes and mate as the a-type partner, whereas MTLα/α cells express α-specific genes and mate as the α-type partner. In this study, we report that the MTLa2 regulator controls the formation of mating projections through both the a- and α-pheromone-sensing pathways and thus results in the bi-mater feature of "α cells" of C. albicans. Ectopic expression of MTLa2 in opaque α cells activates the expression of not only MFA1 and STE3 (a-pheromone receptor) but also MFα1 and STE2 (α-pheromone receptor). Inactivation of either the MFa-Ste3 or MFα-Ste2 pheromone-sensing pathway cannot block the MTLa2-induced development of mating projections. However, the case is different in MTLα1-ectopically expressed opaque a cells. Inactivation of the MFα-Ste2 but not the MFa-Ste3 pheromone-sensing pathway blocks MTLα1-induced development of mating projections. Therefore, MTLa2 and MTLα1 exhibit distinct regulatory features that control the mating response in C. albicans. These findings shed new light on the regulatory mechanism of bi-mating behaviors and sexual reproduction in C. albicans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fgb.2022.103664DOI Listing
April 2022

Rapid detection of Decapod iridescent virus 1 (DIV1) by recombinase polymerase amplification.

J Virol Methods 2022 02 18;300:114362. Epub 2021 Nov 18.

Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture, Guangxi Academy of Fishery Sciences, Nanning, 530021, China. Electronic address:

A recombinase polymerase amplification (RPA) assay was established for the rapid detection of Decapod iridescent virus 1 using primers targeted to the virus's ATPase gene (ORF114R). Optimization experiments showed that the optimal amplification temperature of the RPA assay was 37 °C and that the reaction could be completed within only 15 min. The target band of 15 min. is bright enough. In order to shorten the operational reaction time, consequently, 15 min was the optimal amplification time for our new RPA assay for DIV1. Specificity tests showed that the RPA assay did not exhibit any cross-reactivity with other shrimp pathogens(TSV, MrNV, YHV-1, WSSV, EHP, AHPND, EHNV, RSIV, RGV and IHHNV). Sensitivity tests further showed that the detection limit of the new RPA assay was 200 copies/50 μL, indicating that this assay was more sensitive than a nested polymerase chain reaction (PCR) method. A total of 509 clinical samples were assayed using the RPA and the PCR assays; analysis showed that the RPA method could detect weak-positive samples more effectively than the PCR method. Collectively, these findings indicated that the RPA assay was fast, simple, specific, sensitive and has significant potentials for clinical and on-site testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jviromet.2021.114362DOI Listing
February 2022

A biological and genomic comparison of a drug-resistant and a drug-susceptible strain of isolated from Beijing, China.

Virulence 2021 12;12(1):1388-1399

Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

The fungal pathogen has emerged as a new threat to human health. We previously reported the first isolate of (BJCA001) in China, which belongs to the South Asian clade (I) and was susceptible to all antifungals tested. In this study, we report the isolation of a drug-resistant strain (BJCA002) from the same city (Beijing). Strain BJCA002 belongs to the South African clade (III) and is resistant to fluconazole and amphotericin B based on the tentative MIC breakpoints. Taking advantage of the two isolates with distinct antifungal susceptibility and genetic origins, we performed a biological and genomic comparative study. Besides antifungal susceptibility, strains BJCA001 and BJCA002 showed differences in multiple aspects including morphologies, expression of virulence factors, virulence, mating type, and genomic sequence and organization. Notably, strain BJCA002 was less virulent than BJCA001 in both the and mouse systemic infection models. Genomic analysis demonstrated that strain BJCA002 but not BJCA001 had multiple mutations in drug resistance-associated genes, including a hot-spot mutation of (VF125AL, namely V125A and F126L) and some missense mutations in , and . Notably, strain BJCA001 carried 64 copies of the Zorro3 retrotransposon, whereas BJCA002 had only 3 copies in the genome. Taken together, our findings not only reveal the genetic and phenotypic diversities of the two isolates from Beijing, China, but also shed new light on the genetic basis of the antifungal resistance and virulence of
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21505594.2021.1928410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172162PMC
December 2021

Genomic epidemiology of in a general hospital in Shenyang, China: a three-year surveillance study.

Emerg Microbes Infect 2021 Dec;10(1):1088-1096

National Clinical Research Center for Laboratory Medicine & Department of Laboratory Medicine, the First Hospital of China Medical University, Shenyang, People's Republic of China.

is an emerging pathogenic fungal species found worldwide. Since April 2016, colonization/infection cases have been found in a general hospital in Shenyang, China. The genome-based phylogenetic studies of these isolates remain undefined. In the current study, the microbiological characteristics and antifungal susceptibility of these isolates, which were collected in Shenyang during the three-year period (2016-2018), were investigated. Whole-genome sequencing was applied to investigate the genetic variation and molecular epidemiological characteristics. A total of 93 isolates, including 92 clinical isolates and 1 environmental screening isolate were identified. Among the investigated wards, the cases were the most prevalent (97.4%, 37/38) in four intensive care units (ICUs). The Shenyang isolates carrying the VF125AL mutation in the key drug-resistance gene were mainly fluconazole resistant and formed a distinct subclade under the South African clade according to the phylogenetic and population structural analyses. In addition, the Shenyang subclade was found to be closely related to the British subclade in the aspect of genetic distance. As a conclusion, this study provides an important clue for revealing the origin of found in Shenyang and could also contribute to improve the understanding of the epidemiological characteristics of worldwide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/22221751.2021.1934557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183536PMC
December 2021

Anti-HBV Activities of Polysaccharides from (Küster) by In Vitro and In Vivo Study.

Mar Drugs 2021 Mar 30;19(4). Epub 2021 Mar 30.

Engineering Research Center of Molecular Medicine, Ministry of Education, School of Medicine, Huaqiao University, Xiamen 361021, China.

Hepatitis B virus (HBV) infection remains a major global health problem. It is therefore imperative to develop drugs for anti-hepatitis B with high-efficiency and low toxicity. Attracted by the observations and evidence that the symptoms of some patients from the Southern Fujian, China, suffering from hepatitis B were alleviated after daily eating an edible marine mollusk, (Küster 1860) (TCK). Water-soluble polysaccharide from TCK (TCKP1) was isolated and characterized. The anti-HBV activity of TCKP1 and its regulatory pathway were investigated on both HepG2.2.15 cell line and HBV transgenic mice. The data obtained from in vitro studies showed that TCKP1 significantly enhanced the production of IFN-α, and reduced the level of HBV antigens and HBV DNA in the supernatants of HepG2.2.15 cells in a dose-dependent manner with low cytotoxicity. The result of the study on the HBV transgenic mice further revealed that TCKP1 significantly decreased the level of transaminases, HBsAg, HBeAg, and HBV DNA in the serum, as well as HBsAg, HBeAg, HBV DNA, and HBV RNA in the liver of HBV transgenic (HBV-Tg) mice. Furthermore, TCKP1 exhibited equivalent inhibitory effect with the positive control tenofovir alafenamide (TAF) on the markers above except for HBV DNA even in low dosage in a mouse model. However, the TCKP1 high-dose group displayed stronger inhibition of transaminases and liver HBsAg, HBeAg, and HBV RNA when compared with those of TAF. Meanwhile, inflammation of the liver was, by pathological observation, relieved in a dose-dependent manner after being treated with TCKP1. In addition, elevated levels of interleukin-12 (IL-12) and interferon γ (IFN-γ), and reduced level of interleukin-4 (IL-4) in the serum were observed, indicating that the anti-HBV effect of TCKP1 was achieved by potentiating immunocyte function and regulating the balance of Th1/Th2 cytokines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md19040195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066037PMC
March 2021

Filamentous growth is a general feature of Candida auris clinical isolates.

Med Mycol 2021 Jul;59(7):734-740

Department of Infectious Diseases, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

A striking feature of pathogenic Candida species is morphological plasticity that facilitates environmental adaptation and host infection. Candida auris is an emerging multidrug-resistant fungal pathogen first described in Japan in 2009. In this study, we demonstrate that clinical isolates of C. auris have multiple colony and cellular morphologies including the yeast, filamentous, aggregated, and elongated forms. This phenotypic diversity has been observed in eight clinical isolates of C. auris representing four major genetic clades, suggesting that it could be a general characteristic. We further demonstrate that different cell types of C. auris exhibit distinct antifungal resistance and virulence properties in a Galleria mellonella infection model. Our findings imply that morphological diversity is an important biological feature of C. auris and could be a contributor to its emergence and rapid prevalence worldwide.

Lay Summary: Candida auris is an emerging multidrug-resistant fungal pathogen. Morphological analyses indicate that filamentation is a general feature of clinical isolates of C. auris. This ability is associated with antifungal resistance and virulence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/mmy/myaa116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257410PMC
July 2021

Hepatopancreatic metabolomics shedding light on the mechanism underlying unsynchronized growth in giant freshwater prawn, Macrobrachium rosenbergii.

PLoS One 2020 23;15(12):e0243778. Epub 2020 Dec 23.

College of Animal Science and Technology, Guangxi University, Nanning, Guangxi, China.

The giant freshwater prawn, Macrobrachium rosenbergii (M. rosenbergii) as an important freshwater aquaculture species with high commercial value, exhibited unsynchronized growth. However, the potentially metabolic mechanism remains unclear. In this study, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to investigate the hepatopancreatic metabolic profiles of twenty giant freshwater prawns between the fast-growing group and slow-growing group. In the metabolomics assay, we isolated 8,293 peaks in positive and negative iron mode. Subsequently, 44 significantly differential metabolites were identified. Functional pathway analysis revealed that these metabolites were significantly enriched in three key metabolic pathways. Further integrated analysis indicated that glycerophospholipid metabolism and aminoacyl-tRNA biosynthesis have significant impact on growth performance in M.rosenbergii. Our findings presented here demonstrated the critical metabolites and metabolic pathways involved in growth performance, moreover provided strong evidence for elucidating the potentially metabolic mechanism of the unsynchronized growth in M. rosenbergii.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243778PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757812PMC
January 2021

Candida auris: Epidemiology, biology, antifungal resistance, and virulence.

PLoS Pathog 2020 10 22;16(10):e1008921. Epub 2020 Oct 22.

Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

First described in 2009 in Japan, the emerging multidrug-resistant fungal pathogen Candida auris is becoming a worldwide public health threat that has been attracting considerable attention due to its rapid and widespread emergence over the past decade. The reasons behind the recent emergence of this fungus remain a mystery to date. Genetic analyses indicate that this fungal pathogen emerged simultaneously in several different continents, where 5 genetically distinct clades of C. auris were isolated from distinct geographical locations. Although C. auris belongs to the CTG clade (its constituent species translate the CTG codon as serine instead of leucine, as in the standard code), C. auris is a haploid fungal species that is more closely related to the haploid and often multidrug-resistant species Candida haemulonii and Candida lusitaniae and is distantly related to the diploid and clinically common fungal pathogens Candida albicans and Candida tropicalis. Infections and outbreaks caused by C. auris in hospitals settings have been rising over the past several years. Difficulty in its identification, multidrug resistance properties, evolution of virulence factors, associated high mortality rates in patients, and long-term survival on surfaces in the environment make C. auris particularly problematic in clinical settings. Here, we review progress made over the past decade on the biological and clinical aspects of C. auris. Future efforts should be directed toward understanding the mechanistic details of its biology, epidemiology, antifungal resistance, and pathogenesis with a goal of developing novel tools and methods for the prevention, diagnosis, and treatment of C. auris infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1008921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581363PMC
October 2020

Experimental Evolution Identifies Adaptive Aneuploidy as a Mechanism of Fluconazole Resistance in Candida auris.

Antimicrob Agents Chemother 2020 12 16;65(1). Epub 2020 Dec 16.

Department of Infectious Diseases, Huashan Hospital, and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China

is a newly emerging fungal pathogen of humans and has attracted considerable attention from both the clinical and basic research communities. Clinical isolates of are often resistant to one or more antifungal agents. To explore how antifungal resistance develops, we performed experimental evolution assays using a fluconazole-susceptible isolate of (BJCA001). After a series of passages through medium containing increasing concentrations of fluconazole, fungal cells acquired resistance. By sequencing and comparing the genomes of the parental fluconazole-susceptible strain and 26 experimentally evolved strains of , we found that a portion of fluconazole-resistant strains carried one extra copy of chromosome V. In the absence of fluconazole, cells rapidly became susceptible and lost the extra copy of chromosome V. Genomic and transcriptome sequencing (RNA-Seq) analyses indicate that this chromosome carries a number of drug resistance-related genes, which were transcriptionally upregulated in the resistant, aneuploid strains. Moreover, missense mutations were identified in the genes , , and in all experimentally evolved strains. Our findings suggest that the gain of an extra copy of chromosome V is associated with the rapid acquisition of fluconazole resistance and may represent an important evolutionary mechanism of antifungal resistance in .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01466-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927865PMC
December 2020

Genome-wide analysis of intermuscular bone development reveals changes of key genes expression and signaling pathways in blunt snout bream (Megalobrama amblycephala).

Genomics 2021 01 1;113(1 Pt 2):654-663. Epub 2020 Oct 1.

College of Fisheries, Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education/Key Lab of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, China. Electronic address:

Intermuscular bone (IB) is a hard-boned spicule exist in lower teleost, which brings a lot of detrimental effects on palatability and economic value of blunt snout bream (Megalobrama amblycephala). Masson trichrome staining for ossific IB indicated that some osteoblasts appeared at the edge of the bone matrix and a few osteocytes are present in the center of the mineralized bone matrix. By comparing the orthologous gene families of fish with IBs and without IBs, we screened the key signaling pathways associated with IB formation. Furthermore, the transcriptomic data demonstrated the functional importance of these gene families. The candidate genes involved in chondrocyte development were highly expressed in stage 1 compared with stage 2 and stage 3, suggesting that the development process of IB might mainly involve in intramembranous ossification. Our research reveals the molecular mechanism of IBs formation, and provides molecular evidence for the further study on intermuscular boneless stains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygeno.2020.09.062DOI Listing
January 2021

Discovery of the Diploid Form of the Emerging Fungal Pathogen .

ACS Infect Dis 2020 10 21;6(10):2641-2646. Epub 2020 Sep 21.

Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.

The new multidrug-resistant pathogen was first described in 2009 in Japan and has emerged in many countries worldwide. This human fungal pathogen has long been considered a haploid fungus. Here, we report the discovery of the diploid form and spontaneous ploidy shifts in clinical isolates of . Haploid and diploid cells of differ in several aspects including growth rates, virulence, and global gene expression profiles. For example, diploid cells exhibit a slower growth rate than haploid cells in culture media; however, they are more virulent than haploid cells in a mouse systemic infection model. Global transcriptional expression analysis demonstrates that both haploid and diploid cells express a set of ploidy-enriched genes, which are involved in the regulation of metabolism, cell wall maintenance, translation and DNA replication, and other important biological processes. Antifungal susceptibility testing shows that haploid and diploid cells exhibit similar responses when treated with a number of antifungals. Taken together, haploid and diploid cells may have different fitness responses to diverse niches, and ploidy changes could be an adaptive strategy of to environmental changes. Our findings shed new light on the biology and pathogenesis of this emerging fungal pathogen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsinfecdis.0c00282DOI Listing
October 2020

N-Acetylglucosamine (GlcNAc) Sensing, Utilization, and Functions in .

J Fungi (Basel) 2020 Aug 7;6(3). Epub 2020 Aug 7.

State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.

The sensing and efficient utilization of environmental nutrients are critical for the survival of microorganisms in environments where nutrients are limited, such as within mammalian hosts. is a common member of the human microbiota as well as an opportunistic fungal pathogen. The amide derivative sugar N-acetlyglucosamine (GlcNAc) is an important signaling molecule for that could be a major nutrient source for this fungus in host settings. In this article, we review progress made over the past two decades on GlcNAc utilization, sensing, and functions in and its related fungal species. GlcNAc sensing and catabolic pathways have been intensively studied in . The protein Ngt1 represents the first identified GlcNAc-specific transporter in eukaryotic organisms. In , GlcNAc not only induces morphological transitions including the yeast to hyphal transition and the white to opaque phenotypic switch, but it also promotes fungal cell death. The Ras-cAMP/PKA signaling pathway plays critical roles in regulating these processes. Given the importance of GlcNAc sensing and utilization in , targeting GlcNAc associated pathways and key pathway components could be promising in the development of new antifungal strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jof6030129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558947PMC
August 2020

The PHO pathway regulates white-opaque switching and sexual mating in the human fungal pathogen Candida albicans.

Curr Genet 2020 Dec 5;66(6):1155-1162. Epub 2020 Aug 5.

Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China.

The opportunistic fungal pathogen Candida albicans is able to switch among several morphological phenotypes in response to environmental changes. White-opaque transition is a typical phenotypic switching system involved in the regulation of pathogenesis and sexual reproduction in C. albicans. Under regular laboratory culture conditions, to undergo white-to-opaque switching, cells must first undergo homozygosis at the mating-type locus (MTLa/a or α/α) since the a1/α2 heterodimer represses the expression of the Wor1 master regulator of switching in MTLa/α heterozygous strains. In this study, we report the roles of the PHO pathway of phosphate metabolism in the regulation of white-opaque switching and sexual mating in C. albicans. We find that deletion of the PHO pathway genes PHO81, PHO80, PHO2, and PHO4 induces the opaque phenotype in MTLa/α heterozygous cells. Low concentrations of external phosphate are conducive for the opaque phenotype in both MTL homozygous and heterozygous strains. Moreover, phosphate starvation can also increase the mating efficiency in C. albicans. Consistently, the pho80/pho80 mutant mimics an artificial phosphate starvation state and mates efficiently at both lower and higher phosphate concentrations. Our study establishes a link between the PHO pathway and white-opaque epigenetic switching in C. albicans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00294-020-01100-zDOI Listing
December 2020

The Als3 Cell Wall Adhesin Plays a Critical Role in Human Serum Amyloid A1-Induced Cell Death and Aggregation in Candida albicans.

Antimicrob Agents Chemother 2020 05 21;64(6). Epub 2020 May 21.

Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China

Antimicrobial peptides and proteins play critical roles in the host defense against invading pathogens. We recently discovered that recombinantly expressed human and mouse serum amyloid A1 (rhSAA1 and rmSAA1, respectively) proteins have potent antifungal activities against the major human fungal pathogen At high concentrations, rhSAA1 disrupts membrane integrity and induces rapid fungal cell death. In the present study, we find that rhSAA1 promotes cell aggregation and targets the cell wall adhesin Als3. Inactivation of in leads to a striking decrease in cell aggregation and cell death upon rhSAA1 treatment, suggesting that Als3 plays a critical role in SAA1 sensing. We further demonstrate that deletion of the transcriptional regulators controlling the expression of , such as , , and , in results in similar effects to that of the mutant upon rhSAA1 treatment. Global gene expression profiling indicates that rhSAA1 has a discernible impact on the expression of cell wall- and metabolism-related genes, suggesting that rhSAA1 treatment could lead to a nutrient starvation effect on cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.00024-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269472PMC
May 2020

Genetic regulation of the development of mating projections in .

Emerg Microbes Infect 2020 21;9(1):413-426. Epub 2020 Feb 21.

Department of infectious diseases, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

is a major human fungal pathogen, capable of switching among a range of morphological types, such as the yeast form, including white and opaque cell types and the GUT (gastrointestinally induced transition) cell type, the filamentous form, including hyphal and pseudohyphal cell types, and chlamydospores. This ability is associated with its commensal and pathogenic life styles. In response to pheromone, cells are able to form long mating projections resembling filaments. This filamentous morphology is required for efficient sexual mating. In the current study, we report the genetic regulatory mechanisms controlling the development of mating projections in . Ectopic expression of α1 in "" cells induces the secretion of α-pheromone and promotes the development of mating projections. Using this inducible system, we reveal that members of the pheromone-sensing pathway (including the pheromone receptor), the Ste11-Hst7-Cek1/2 mediated MAPK signalling cascade, and the RAM pathway are essential for the development of mating projections. However, the cAMP/PKA signalling pathway and a number of key regulators of filamentous growth such as Hgc1, Efg1, Flo8, Tec1, Ume6, and Rfg1 are not required for mating projection formation. Therefore, despite the phenotypic similarities between filaments and mating projections in , distinct mechanisms are involved in the regulation of these two morphologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/22221751.2020.1729067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048184PMC
March 2020

Biological and genomic analyses of a clinical isolate of Yarrowia galli from China.

Curr Genet 2020 Jun 21;66(3):549-559. Epub 2019 Dec 21.

Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China.

Infections caused by emerging fungal pathogens represent a new threat to human health. The yeast Yarrowia (Candida) galli was first described from chicken breast and liver in 2004 and has occasionally been isolated in clinical settings. In this study, we present the first report of a Y. galli isolate from a face granuloma of a woman. Y. galli is unable to grow at human physiological temperature (37 °C). Phenotypic analysis demonstrates that Y. galli can exist as several morphological types, namely fluffy, sticky, tight, and yeast forms, based on their cellular and colony appearances. Interestingly, Y. galli is able to undergo switching among different morphologies. These morphological changes are similar to the switching systems in pathogenic Candida species such as Candida albicans and Candida tropicalis. We further sequenced the genome of the Y. galli isolate. A comparative analysis with pathogenic yeast species indicated that a set of lipid metabolism genes were enriched in Y. galli. Domain enrichment analysis demonstrated that, similar to Candida clade species, the genome of Y. galli maintained several gene families required for virulence. Our biological and genomic analyses provide new insights into the understanding of the biology of Y. galli as either an environmental isolate or a potential human pathogen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00294-019-01046-xDOI Listing
June 2020

Comparative Transcriptome Analysis of Gonads for the Identification of Sex-Related Genes in Giant Freshwater Prawns ( ) Using RNA Sequencing.

Genes (Basel) 2019 12 11;10(12). Epub 2019 Dec 11.

College of Animal Science and Technology, Guangxi University, Nanning 530001, China.

The giant freshwater prawn ( ) exhibits sex dimorphism between the male and female individuals. To date, the molecular mechanism governing gonadal development was unclear, and limited data were available on the gonad transcriptome of . Here, we conducted comprehensive gonadal transcriptomic analysis of female (ZW), super female (WW), and male (ZZ) for gene discovery. A total of 70.33 gigabases (Gb) of sequences were generated. There were 115,338 unigenes assembled with a mean size of 1,196 base pair (bp) and N50 of 2,195 bp. Alignment against the National Center for Biotechnology Information (NCBI) non-redundant nucleotide/protein sequence database (NR and NT), the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, SwissProt database, Protein family (Pfam), Gene ontology (GO), and the eukaryotic orthologous group (KOG) database, 36,282 unigenes were annotated at least in one database. Comparative transcriptome analysis observed that 10,641, 16,903, and 3,393 genes were significantly differentially expressed in ZW vs. ZZ, WW vs. ZZ, and WW vs. ZW samples, respectively. Enrichment analysis of differentially expressed genes (DEGs) resulted in 268, 153, and 42 significantly enriched GO terms, respectively, and a total of 56 significantly enriched KEGG pathways. Additionally, 23 putative sex-related genes, including Gtsf1, IR, HSP21, MRPINK, Mrr, and other potentially promising candidate genes were identified. Moreover, 56,241 simple sequence repeats (SSRs) were identified. Our findings provide a valuable archive for further functional analyses of sex-related genes and future discoveries of underlying molecular mechanisms of gonadal development and sex determination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes10121035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947849PMC
December 2019

Transcriptomics of Cherax quadricarinatus hepatopancreas during infection with Decapod iridescent virus 1 (DIV1).

Fish Shellfish Immunol 2020 Mar 21;98:832-842. Epub 2019 Nov 21.

Nanning University, Nanning, 530200, Guangxi, China. Electronic address:

Cherax quadricarinatus is a large-sized, highly fecund, and fast-growing species of freshwater crayfish, and has become one of the world's most intensely studied crustaceans. Decapod iridescent virus 1 (DIV1), a newly described species in the family Iridoviridae, is known to infect various crustaceans, including C. quadricarinatus, and may pose a new threat in the shrimp-farming industry. The present study performed de novo transcriptome sequencing of C. quadricarinatus hepatopancreas during DIV1 infection. A total of 114,784 transcripts and 56,418 genes were obtained; 1070 genes were upregulated and 775 genes were downregulated when compared with the uninfected samples (controls). Three pattern recognition receptor genes (fibrinogen-related protein, C-type lectin, and beta-1,3-glucan-binding protein) were upregulated during DIV1 infection. Among the top-30 upregulated unigenes, 9 unigenes were identified as vitellogenin (Vg) genes, and the top-3 upregulated unigenes were identified as involved in Vg lipid transport, lipid localization, and lipid transporter activity, which were all significantly over-representative GO terms in the GO enrichment analysis of total and upregulated differentially expressed genes (DEGs). Many genes associated with Jak-STAT signaling pathway, Endocytosis, Phagosome, MAPK signaling pathway, Apoptosis and Lysosome were positively modified after DIV1 infection. The predicted protein-protein interaction (PPI) analysis showed NF1 and TUBA, CRM1 and TUBB were involved in protein interactions. This research showed that DIV1 infection has a significant impact on the transcriptome profile of C. quadricarinatus hepatopancreas, and the results enhance our understanding of virus-host interactions. Furthermore, the high number of transcripts generated in the present study will provide information for identifying novel genes in the absence of a full C. quadricarinatus genome sequence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsi.2019.11.041DOI Listing
March 2020

Antifungal Activity of Mammalian Serum Amyloid A1 against .

Antimicrob Agents Chemother 2019 12 20;64(1). Epub 2019 Dec 20.

Department of Infectious Diseases, Huashan Hospital, Fudan University and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China

Mammalian serum amyloid A (SAA) is a major acute phase protein that shows a massive increase in plasma concentration during inflammation. In the present study, we demonstrate that the expression of mouse SAA1 in serum was increased when infected with , a major human fungal pathogen, in a systemic infection model. We then set out to investigate the antifungal activity of SAA proteins against Recombinant human and mouse SAA1 (rhSAA1 and rmSAA1) were expressed and purified in Both rhSAA1 and rmSAA1 exhibited a potent antifungal activity against We further demonstrate that rhSAA1 binds to the cell surface of , disrupts cell membrane integrity, and induces rapid fungal cell death in Our finding expands the known functions of SAA1 and provides new insight into host- interactions during fungal infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01975-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187584PMC
December 2019

Establishment of pyrosequencing technology to detect White Spot Syndrome Virus (WSSV) in cultured aquatic animals.

J Virol Methods 2019 11 5;273:113683. Epub 2019 Jul 5.

Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture, Academy of Fishery Sciences, Nanning, Guangxi 530021, China. Electronic address:

This study aimed to establish pyrosequencing methods to detect white spot syndrome virus (WSSV). One pair of polymerase chain reaction (PCR) primers, and one pyrosequencing primer, were designed for WSSV. The pyrosequencing reaction system and conditions were optimized and a pyrosequencing method for detecting WSSV was successfully established. This method was able to specifically detect WSSV in eight viruses, with high sensitivity. The minimum detectable limit for nucleic acid was 23 copies/μL. The method was verified by detecting WSSV in 1881 batches of samples collected from domestic and imported shrimps. The detection results were more sensitive than conventional PCR. This research has therefore provided a new detection method for monitoring, and controlling aquatic animal virus diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jviromet.2019.113683DOI Listing
November 2019

No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients.

Intervirology 2018 24;61(6):281-291. Epub 2019 Apr 24.

Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China,

Objectives: The epidemiological evidence is inconsistent about whether HIV-positive injection drug users (IDUs) are at higher risk of developing antiretroviral resistance than any other HIV-positive populations. This study aims to investigate and compare transmitted drug resistance (TDR) between IDUs and non-IDUs in Lingshan County, an HIV-hit region in Guangxi, China, where IDU and heterosexual transmission were the two dominant transmission routes and roughly equally contributed to the local HIV transmission.

Methods: A cross-sectional study was conducted among newly diagnosed and antiretroviral-treatment (ART)-naïve HIV-1 patients from Lingshan County. The pol gene of HIV-1 from the individuals was sequenced followed by genotyping and TDR analysis.

Results: Two dominant transmission routes, heterosexual contact and IDU, accounted for 49.2 and 45.9% of 183 HIV-1 infection cases, respectively. Three genotypes, including CRF08_BC (70.6%), CRF01_AE (24.4%), and CRF07_BC (5.0%), and three unique recombinant forms (1.6%), were identified. There was a significant difference in genotype distribution among the different transmission routes (F = 21.814, p < 0.001). The overall TDR prevalence was 5.5%. There were no significant differences in TDR prevalence among the different transmission routes (F = 1.420, p = 0.439).

Conclusions: Injection drug use has little impact on TDR prevalence compared with other routes of transmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000499367DOI Listing
September 2019

The general transcriptional repressor Tup1 governs filamentous development in Candida tropicalis.

Acta Biochim Biophys Sin (Shanghai) 2019 May;51(5):463-470

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

Filamentous development is associated with the ability to cause infections and colonize the host in pathogenic Candida species. Candida tropicalis is one of the major fungal pathogens of humans. The conserved transcriptional repressor Tup1 plays a critical role in the regulation of transcription and filamentation in yeast species. Despite its central role, the full coding sequence of TUP1 has not been found in the reported genome sequence of C. tropicalis to date. In this study, we report the identification of Tup1 and characterize its role in filamentous growth in C. tropicalis. As expected, C. tropicalis Tup1 exhibits general conserved features to the orthologs of other fungi in terms of its structure and function. Deletion of TUP1 in C. tropicalis leads to increased filamentation under several culture conditions. However, Tup1 indeed exhibits species-specific roles in the regulation of filamentous development in C. tropicalis. For example, unlike the tup1/tup1 mutant of Candida albicans, the tup1/tup1 mutant of C. tropicalis is able to exist in the yeast form at low temperatures or in the presence of N-acetylglucosamine (GlcNAc). Acidic pH conditions also favor the yeast form of the tup1/tup1 mutant of C. tropicalis. Quantitative real-time PCR (qRT-PCR) assays indicate that Tup1 may regulate filamentous development through the transcriptional control of key filamentation regulators in C. tropicalis, such as Ume6, Brg1, Wor1, Sfl2, Ahr1, and Zcf3. Taken together, our findings demonstrate both conserved and species-specific roles of Tup1 in the regulation of filamentation and provide novel insights into the biology of C. tropicalis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/abbs/gmz023DOI Listing
May 2019

Environment-induced same-sex mating in the yeast Candida albicans through the Hsf1-Hsp90 pathway.

PLoS Biol 2019 03 13;17(3):e2006966. Epub 2019 Mar 13.

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

While sexual reproduction is pervasive in eukaryotic cells, the strategies employed by fungal species to achieve and complete sexual cycles is highly diverse and complex. Many fungi, including Saccharomyces cerevisiae and Schizosaccharomyces pombe, are homothallic (able to mate with their own mitotic descendants) because of homothallic switching (HO) endonuclease-mediated mating-type switching. Under laboratory conditions, the human fungal pathogen Candida albicans can undergo both heterothallic and homothallic (opposite- and same-sex) mating. However, both mating modes require the presence of cells with two opposite mating types (MTLa/a and α/α) in close proximity. Given the predominant clonal feature of this yeast in the human host, both opposite- and same-sex mating would be rare in nature. In this study, we report that glucose starvation and oxidative stress, common environmental stresses encountered by the pathogen, induce the development of mating projections and efficiently permit same-sex mating in C. albicans with an "a" mating type (MTLa/a). This induction bypasses the requirement for the presence of cells with an opposite mating type and allows efficient sexual mating between cells derived from a single progenitor. Glucose starvation causes an increase in intracellular oxidative species, overwhelming the Heat Shock transcription Factor 1 (Hsf1)- and Heat shock protein (Hsp)90-mediated stress-response pathway. We further demonstrate that Candida TransActivating protein 4 (Cta4) and Cell Wall Transcription factor 1 (Cwt1), downstream effectors of the Hsf1-Hsp90 pathway, regulate same-sex mating in C. albicans through the transcriptional control of the master regulator of a-type mating, MTLa2, and the pheromone precursor-encoding gene Mating α factor precursor (MFα). Our results suggest that mating could occur much more frequently in nature than was originally appreciated and that same-sex mating could be an important mode of sexual reproduction in C. albicans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pbio.2006966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415874PMC
March 2019

Filamentation in Candida auris, an emerging fungal pathogen of humans: passage through the mammalian body induces a heritable phenotypic switch.

Emerg Microbes Infect 2018 Nov 28;7(1):188. Epub 2018 Nov 28.

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.

Morphological plasticity has historically been an indicator of increased virulence among fungal pathogens, allowing rapid adaptation to changing environments. Candida auris has been identified as an emerging multidrug-resistant human pathogen of global importance. Since the discovery of this species, it has been thought that C. auris is incapable of filamentous growth. Here, we report the discovery of filamentation and three distinct cell types in C. auris: typical yeast, filamentation-competent (FC) yeast, and filamentous cells. These cell types form a novel phenotypic switching system that contains a heritable (typical yeast-filament) and a nonheritable (FC-filament) switch. Intriguingly, the heritable switch between the typical yeast and the FC/filamentous phenotype is triggered by passage through a mammalian body, whereas the switch between the FC and filamentous phenotype is nonheritable and temperature-dependent. Low temperatures favor the filamentous phenotype, whereas high temperatures promote the FC yeast phenotype. Systemic in vivo and in vitro investigations were used to characterize phenotype-specific variations in global gene expression, secreted aspartyl proteinase (SAP) activity, and changes in virulence, indicating potential for niche-specific adaptations. Taken together, our study not only sheds light on the pathogenesis and biology of C. auris but also provides a novel example of morphological and epigenetic switching in fungi.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41426-018-0187-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258701PMC
November 2018
-->