Soo Chan Lee

@utsa.edu/sciences/molecular-microbiology-immunology

Molecular Microbiology and Immunology
University of Texas at San Antonio



              

https://researchid.co/juststart
44

Scopus Publications

2829

Scholar Citations

23

Scholar h-index

35

Scholar i10-index

Scopus Publications

  • Weissella sp. SNUL2 as potential probiotics with broad-spectrum antimicrobial activities
    Jae Won Han, Nari Lee, Hea Joon Kim, Sung Jin Moon, Soo Chan Lee, and Hyo Jin Kim
    Elsevier BV

  • The players within the intestinal microbiome (bacteria, fungi, parasites, and viruses)
    Jintong Liu, Marie Fogarty, Soo Chan Lee, Michael Dougherty, Renay Ngobeni-Nyambi, Yi Ge, and Ian M. Carroll
    Springer Nature Switzerland

  • Transcription Factors Tec1 and Tec2 Play Key Roles in the Hyphal Growth and Virulence of Mucor lusitanicus Through Increased Mitochondrial Oxidative Metabolism
    Viridiana Alejandre-Castañeda, J. Alberto Patiño-Medina, Marco I. Valle-Maldonado, Alexis García, Rafael Ortiz-Alvarado, León F. Ruíz-Herrera, Karla Viridiana Castro-Cerritos, Joel Ramírez-Emiliano, Martha I. Ramírez-Díaz, Victoriano Garre,et al.
    Springer Science and Business Media LLC

  • Serine/Threonine Phosphatase Calcineurin Orchestrates the Intrinsic Resistance to Micafungin in the Human-Pathogenic Fungus Mucor circinelloides
    Alexis Garcia, Eun Young Huh, and Soo Chan Lee
    American Society for Microbiology
    Procedures such as solid-organ transplants and cancer treatments can leave many patients in an immunocompromised state. This leads to their increased susceptibility to opportunistic diseases such as fungal infections.

  • Compositional changes in fecal microbiota associated with clinical phenotypes and prognosis in Korean patients with inflammatory bowel disease
    Seung Yong Shin, Young Kim, Won-Seok Kim, Jung Min Moon, Kang-Moon Lee, Sung-Ae Jung, Hyesook Park, Eun Young Huh, Byung Chang Kim, Soo Chan Lee,et al.
    Korean Association for the Study of Intestinal Diseases
    Background/Aims: The fecal microbiota of Korean patients with inflammatory bowel disease (IBD) was investigated with respect to disease phenotypes and taxonomic biomarkers for diagnosis and prognosis of IBD.Methods: Fecal samples from 70 ulcerative colitis (UC) patients, 39 Crohn’s disease (CD) patients, and 100 healthy control individuals (HC) were collected. The fecal samples were amplified via polymerase chain reaction and sequenced using Illumina MiSeq. The relationships between fecal bacteria and clinical phenotypes were analyzed using the EzBioCloud database and 16S microbiome pipeline.Results: The alpha-diversity of fecal bacteria was significantly lower in UC and CD (<i>P</i><0.05) compared to that in HC. Bacterial community compositions in UC and CD were significantly different from that of HC according to Bray-Curtis dissimilarities, and there was also a difference between community composition in UC and CD (<i>P</i>=0.01). In UC, alpha-diversity was further decreased when the disease was more severe and the extent of disease was greater, and community composition significantly differed depending on the extent of the disease. We identified 9 biomarkers of severity and 6 biomarkers of the extent of UC. We also identified 5 biomarkers of active disease and 3 biomarkers of ileocolonic involvement in CD. <i>Lachnospiraceae</i> and <i>Ruminococcus gnavus</i> were biomarkers for better prognosis in CD.Conclusions: The fecal microbiota profiles of IBD patients were different from those of HC, and several bacterial taxa may be used as biomarkers to determine disease phenotypes and prognosis. These data may also help discover new therapeutic targets for IBD.

  • Current treatments against mucormycosis and future directions
    Courtney Smith and Soo Chan Lee
    Public Library of Science (PLoS)
    Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of fungi belonging to the order Mucorales. These molds exist throughout the environment and generally do not cause serious problems in humans. Mucormycosis mainly affects individuals who are immunocompromised. The clinical manifestations of mucormycosis are wide-ranging; they include sinusitis (pansinusitis, rhino-orbital, or rhino-cerebral) as well as cutaneous, gastrointestinal, pulmonary, and disseminate infections. Many uncertainties remain regarding how to control these infections despite the recent addition of triazoles to the antifungal arsenal for treating this infection. Currently, lipid formulations of amphotericin B have become the standard treatment for mucormycosis due to their efficiency. Moreover, a growing body of data supports the need for surgical excision of infected and/or necrosed tissue whenever practical. In this mini review, the current status of treatment options for mucormycosis and recent studies of novel therapeutic options will be presented.

  • Identification of Mucormycosis by Fluorescence In Situ Hybridization Targeting Ribosomal RNA in Tissue Samples
    Jill Jasmine Dalimot, Ilka Mc Cormick Smith, Jasmin Gerkrath, Sylvia Hartmann, Oliver A. Cornely, Soo Chan Lee, Joseph Heitman, and Volker Rickerts
    MDPI AG
    Mucormycosis is an invasive fungal infection associated with high mortality, partly due to delayed diagnosis and inadequate empiric therapy. As fungal cultures often fail to grow Mucorales, identification of respective hyphae in tissue is frequently needed for diagnosis but may be challenging. We studied fluorescence in situ hybridization (FISH) targeting specific regions of the fungal ribosomal RNA (rRNA) of Mucorales to improve diagnosis of mucormycosis from tissue samples. We generated a probe combination specifically targeting Mucorales. Probe specificity was verified in silico and using cultivated fungi. Mucorales hyphae in tissue of a mouse model demonstrated a bright cytoplasmatic hybridization signal. In tissue samples of patients with mucormycosis, a positive signal was seen in 7 of 12 (58.3%) samples. However, autofluorescence in 3 of 7 (42.9%) samples impaired the diagnostic yield. Subsequent experiments suggested that availability of nutrients and antifungal therapy may impact on the FISH signal obtained with Mucorales hyphae. Diagnosis of mucormycosis from tissue might be improved by rRNA FISH in a limited number of cases only. FISH signals may reflect different physiological states of fungi in tissue. Further studies are needed to define the value of FISH to diagnose mucormycosis from other clinical samples.

  • Interactions of FK506 and Rapamycin With FK506 Binding Protein 12 in Opportunistic Human Fungal Pathogens
    Sandeep Vellanki, Alexis E. Garcia, and Soo Chan Lee
    Frontiers Media SA
    Over the past few decades advances in modern medicine have resulted in a global increase in the prevalence of fungal infections. Particularly people undergoing organ transplants or cancer treatments with a compromised immune system are at an elevated risk for lethal fungal infections such as invasive candidiasis, aspergillosis, cryptococcosis, etc. The emergence of drug resistance in fungal pathogens poses a serious threat to mankind and it is critical to identify new targets for the development of antifungals. Calcineurin and TOR proteins are conserved across eukaryotes including pathogenic fungi. Two small molecules FK506 and rapamycin bind to FKBP12 immunophilin and the resulting complexes (FK506-FKBP12 and rapamycin-FKBP12) target calcineurin and TOR, respectively in both humans and fungi. However, due to their immunosuppressive nature these drugs in the current form cannot be used as an antifungal. To overcome this, it is important to identify key differences between human and fungal FKBP12, calcineurin, and TOR proteins which will facilitate the development of new small molecules with higher affinity toward fungal components. The current review highlights FK506/rapamycin-FKBP12 interactions with calcineurin/TOR kinase in human and fungi, and development of non-immunosuppressive analogs of FK506, rapamycin, and novel small molecules in inhibition of fungal calcineurin and TOR kinase.

  • The heterotrimeric G-protein beta subunit Gpb1 controls hyphal growth under low oxygen conditions through the protein kinase A pathway and is essential for virulence in the fungus Mucor circinelloides
    Marco Iván Valle‐Maldonado, José Alberto Patiño‐Medina, Carlos Pérez‐Arques, Nancy Yadira Reyes‐Mares, Irvin Eduardo Jácome‐Galarza, Rafael Ortíz‐Alvarado, Sandeep Vellanki, Martha Isela Ramírez‐Díaz, Soo Chan Lee, Victoriano Garre,et al.
    Hindawi Limited
    Mucor circinelloides, a dimorphic opportunistic pathogen, expresses three heterotrimeric G-protein beta subunits (Gpb1, Gpb2, Gpb3). The Gpb1-encoding gene is upregulated during mycelial growth compared with that in the spore or yeast stage. gpb1 deletion mutation analysis revealed its relevance for an adequate development during the dimorphic transition and for hyphal growth under low oxygen concentrations. Infection assays in mice indicated a phenotype with considerably reduced virulence and tissue invasiveness in the deletion mutants (Δgpb1) and decreased host inflammatory response. This finding could be attributed to the reduced filamentous growth in animal tissues compared with that of the wild-type strain. Mutation in a regulatory subunit of cAMP-dependent protein kinase A (PKA) subunit (PkaR1) resulted in similar phenotypes to Δgpb1. The defects exhibited by the Δgpb1 strain were genetically suppressed by pkaR1 overexpression, indicating that the PKA pathway is controlled by Gpb1 in M. circinelloides. Moreover, during growth under low oxygen levels, cAMP levels were much higher in the Δgpb1 than in the wild-type strain, but similar to those in the ΔpkaR1 strain. These findings reveal that M. circinelloides possesses a signal transduction pathway through which the Gpb1 heterotrimeric G subunit and PkaR1 control mycelial growth in response to low oxygen levels. This article is protected by copyright. All rights reserved.

  • Increased accumulation of medium-chain fatty acids by dynamic degradation of long-chain fatty acids in mucor circinelloides
    Syed Ammar Hussain, Alexis Garcia, Md. Ahsanul Kabir Khan, Shaista Nosheen, Yao Zhang, Mattheos A. G. Koffas, Victoriano Garre, Soo Chan Lee, and Yuanda Song
    MDPI AG
    Concerns about global warming, fossil-fuel depletion, food security, and human health have promoted metabolic engineers to develop tools/strategies to overproduce microbial functional oils directly from renewable resources. Medium-chain fatty acids (MCFAs, C8–C12) have been shown to be important sources due to their diverse biotechnological importance, providing benefits ranging from functional lipids to uses in bio-fuel production. However, oleaginous microbes do not carry native pathways for the production of MCFAs, and therefore, diverse approaches have been adapted to compensate for the requirements of industrial demand. Mucor circinelloides is a promising organism for lipid production (15–36% cell dry weight; CDW) and the investigation of mechanisms of lipid accumulation; however, it mostly produces long-chain fatty acids (LCFAs). To address this challenge, we genetically modified strain M. circinelloides MU758, first by integrating heterologous acyl-ACP thioesterase (TE) into fatty acid synthase (FAS) complex and subsequently by modifying the β-oxidation pathway by disrupting the acyl-CoA oxidase (ACOX) and/or acyl-CoA thioesterase (ACOT) genes with a preference for medium-chain acyl-CoAs, to elevate the yield of MCFAs. The resultant mutant strains (M-1, M-2, and M-3, respectively) showed a significant increase in lipid production in comparison to the wild-type strain (WT). MCFAs in M-1 (47.45%) was sharply increased compared to the wild type strain (2.25%), and it was further increased in M-2 (60.09%) suggesting a negative role of ACOX in MCFAs production. However, MCFAs in M-3 were much decreased compared to M-1,suggesting a positive role of ACOT in MCFAs production. The M-2 strain showed maximum lipid productivity (~1800 milligram per liter per day or mg/L.d) and MCFAs productivity (~1100 mg/L.d). Taken together, this study elaborates on how the combination of two multidimensional approaches, TE gene over-expression and modification of the β-oxidation pathway via substantial knockout of specific ACOX gene, significantly increased the production of MCFAs. This synergistic approach ultimately offers a novel opportunity for synthetic/industrial biologists to increase the content of MCFAs.

  • Tornadic shear stress induces a transient, calcineurindependent hypervirulent phenotype in mucorales molds
    Sebastian Wurster, Alexander M. Tatara, Nathaniel D. Albert, Ashraf S. Ibrahim, Joseph Heitman, Soo Chan Lee, Amol C. Shetty, Carrie McCracken, Karen T. Graf, Antonios G. Mikos,et al.
    American Society for Microbiology
    Given the limited efficacy of current medical treatments in trauma-related necrotizing mucormycosis, there is a dire need to better understand the Mucoralean pathophysiology in order to develop novel strategies to counteract fungal tissue invasion following severe trauma. Here, we describe that tornadic shear stress challenge transiently induces a hypervirulent phenotype in various pathogenic Mucorales species but not in other molds known to cause wound infections. Pharmacological and genetic inhibition of calcineurin signaling abrogated hypervirulence in shear stress-challenged Mucorales, encouraging further evaluation of (topical) calcineurin inhibitors to improve therapeutic outcomes of NMM after combat-related blast injuries or violent storms.

  • A novel resistance pathway for calcineurin inhibitors in the human-pathogenic mucorales mucor circinelloides
    Sandeep Vellanki, R. Blake Billmyre, Alejandra Lorenzen, Micaela Campbell, Broderick Turner, Eun Young Huh, Joseph Heitman, and Soo Chan Lee
    American Society for Microbiology
    Mucor is intrinsically resistant to most known antifungals, which makes mucormycosis treatment challenging. Calcineurin is a serine/threonine phosphatase that is widely conserved across eukaryotes. When calcineurin function is inhibited in Mucor , growth shifts to a less virulent yeast growth form, which makes calcineurin an attractive target for development of new antifungal drugs. Previously, we identified two distinct mechanisms through which Mucor can become resistant to calcineurin inhibitors involving Mendelian mutations in the gene for FKBP12, including mechanisms corresponding to calcineurin A or B subunits and epimutations silencing the FKBP12 gene. Here, we identified a third novel mechanism where loss-of-function mutations in the amino acid permease corresponding to the bycA gene contribute to resistance against calcineurin inhibitors. When calcineurin activity is absent, BycA can activate protein kinase A (PKA) to promote yeast growth via a cAMP-independent pathway. Our data also show that calcineurin activity contributes to host-pathogen interactions primarily in the pathogenesis of Mucor.

  • mSphere of influence: The mycobiota in human health and disease
    Soo Chan Lee
    American Society for Microbiology
    Soo Chan Lee works in the field of medical mycology. In this mSphere of Influence article, he reflects on how “Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis” (Science 336:1314–1317, 2012, https://doi.org/10.1126/science.1221789 ) by I. D. Iliev, V. A. Funari, K. D. Taylor, Q.

  • Heterotrimeric G-alpha subunits Gpa11 and Gpa12 define a transduction pathway that control spore size and virulence in Mucor circinelloides
    J. Alberto Patiño-Medina, Nancy Y. Reyes-Mares, Marco I. Valle-Maldonado, Irvin E. Jácome-Galarza, Carlos Pérez-Arques, Rosa E. Nuñez-Anita, Jesús Campos-García, Verónica Anaya-Martínez, Rafael Ortiz-Alvarado, Martha I. Ramírez-Díaz,et al.
    Public Library of Science (PLoS)
    Mucor circinelloides is one of the causal agents of mucormycosis, an emerging and high mortality rate fungal infection produced by asexual spores (sporangiospores) of fungi that belong to the order Mucorales. M. circinelloides has served as a model genetic system to understand the virulence mechanism of this infection. Although the G-protein signaling cascade plays crucial roles in virulence in many pathogenic fungi, its roles in Mucorales are yet to be elucidated. Previous study found that sporangiospore size and calcineurin are related to the virulence in Mucor, in which larger spores are more virulent in an animal mucormycosis model and loss of a calcineurin A catalytic subunit CnaA results in larger spore production and virulent phenotype. The M. circinelloides genome is known to harbor twelve gpa (gpa1 to gpa12) encoding G-protein alpha subunits and the transcripts of the gpa11 and gpa12 comprise nearly 72% of all twelve gpa genes transcript in spores. In this study we demonstrated that loss of function of Gpa11 and Gpa12 led to larger spore size associated with reduced activation of the calcineurin pathway. Interestingly, we found lower levels of the cnaA mRNAs in sporangiospores from the Δgpa12 and double Δgpa11/Δgpa12 mutant strains compared to wild-type and the ΔcnaA mutant had significantly lower gpa11 and gpa12 mRNA levels compared to wild-type. However, in contrast to the high virulence showed by the large spores of ΔcnaA, the spores from Δgpa11/Δgpa12 were avirulent and produced lower tissue invasion and cellular damage, suggesting that the gpa11 and gpa12 define a signal pathway with two branches. One of the branches controls spore size through regulation of calcineurin pathway, whereas virulences is controlled by an independent pathway. This virulence-related regulatory pathway could control the expression of genes involved in cellular responses important for virulence, since sporangiospores of Δgpa11/Δgpa12 were less resistant to oxidative stress and phagocytosis by macrophages than the ΔcnaA and wild-type strains. The characterization of this pathway could contribute to decipher the signals and mechanism used by Mucorales to produce mucormycosis.

  • Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents
    Praveen R. Juvvadi, David Fox, Benjamin G. Bobay, Michael J. Hoy, Sophie M. C. Gobeil, Ronald A. Venters, Zanetta Chang, Jackie J. Lin, Anna Floyd Averette, D. Christopher Cole,et al.
    Springer Science and Business Media LLC
    AbstractCalcineurin is important for fungal virulence and a potential antifungal target, but compounds targeting calcineurin, such as FK506, are immunosuppressive. Here we report the crystal structures of calcineurin catalytic (CnA) and regulatory (CnB) subunits complexed with FK506 and the FK506-binding protein (FKBP12) from human fungal pathogens (Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans and Coccidioides immitis). Fungal calcineurin complexes are similar to the mammalian complex, but comparison of fungal and human FKBP12 (hFKBP12) reveals conformational differences in the 40s and 80s loops. NMR analysis, molecular dynamic simulations, and mutations of the A. fumigatus CnA/CnB-FK506-FKBP12-complex identify a Phe88 residue, not conserved in hFKBP12, as critical for binding and inhibition of fungal calcineurin. These differences enable us to develop a less immunosuppressive FK506 analog, APX879, with an acetohydrazine substitution of the C22-carbonyl of FK506. APX879 exhibits reduced immunosuppressive activity and retains broad-spectrum antifungal activity and efficacy in a murine model of invasive fungal infection.

  • Epigenetic mechanisms of drug resistance in fungi
    Zanetta Chang, V. Yadav, Soo Chan Lee and J. Heitman



  • Maternal exercise before and during pregnancy alleviates metabolic dysfunction associated with high-fat diet in pregnant mice, without significant changes in gut microbiota
    Eunhee Chung, Katherine A. Grue, Gurvinder Kaur, Brian Mallory, Christian R. Serrano, Sarah L. Ullevig, Kameswara Rao Kottapalli, Soo Chan Lee, Jannette M. Dufour, Chwan-Li Shen,et al.
    Elsevier BV

  • Gastrointestinal microbiota alteration induced by Mucor circinelloides in a murine model
    Katherine D. Mueller, Hao Zhang, Christian R. Serrano, R. Blake Billmyre, Eun Young Huh, Philipp Wiemann, Nancy P. Keller, Yufeng Wang, Joseph Heitman, and Soo Chan Lee
    Springer Science and Business Media LLC

  • Candida albicans morphology-dependent host fgf-2 response as a potential therapeutic target
    S. Vellanki, E. Huh, S. Saville and Soo Chan Lee

    Angiogenesis mediated by proteins such as Fibroblast Growth Factor-2 (FGF-2) is a vital component of normal physiological processes and has also been implicated in contributing to the disease state associated with various microbial infections. Previous studies by our group and others have shown that Candida albicans, a common agent of candidiasis, induces FGF-2 secretion in vitro and angiogenesis in brains and kidneys during systemic infections. However, the underlying mechanism(s) via which the fungus increases FGF-2 production and the role(s) that FGF-2/angiogenesis plays in C. albicans disease remain unknown. Here we show, for the first time, that C. albicans hyphae (and not yeast cells) increase the FGF-2 response in human endothelial cells. Moreover, Candidalysin, a toxin secreted exclusively by C. albicans in the hyphal state, is required to induce this response. Our in vivo studies show that in the systemic C. albicans infection model, mice treated with FGF-2 exhibit significantly higher mortality rates when compared to untreated mice not given the angiogenic growth factor. Even treatment with fluconazole could not fully rescue infected animals that were administered FGF-2. Our data suggest that the increase of FGF-2 production/angiogenesis induced by Candidalysin contributes to the pathogenicity of C. albicans.

  • CRISPR-Cas9 induces point mutation in the mucormycosis fungus Rhizopus delemar
    Gillian O. Bruni, Keili Zhong, Soo Chan Lee, and Ping Wang
    Elsevier BV

  • Broad antifungal resistance mediated by RNAi-dependent epimutation in the basal human fungal pathogen Mucor circinelloides
    Zanetta Chang, R. Blake Billmyre, Soo Chan Lee, and Joseph Heitman
    Public Library of Science (PLoS)
    Mucormycosis - an emergent, deadly fungal infection - is difficult to treat, in part because the causative species demonstrate broad clinical antifungal resistance. However, the mechanisms underlying drug resistance in these infections remain poorly understood. Our previous work demonstrated that one major agent of mucormycosis, Mucor circinelloides, can develop resistance to the antifungal agents FK506 and rapamycin through a novel, transient RNA interference-dependent mechanism known as epimutation. Epimutations silence the drug target gene and are selected by drug exposure; the target gene is re-expressed and sensitivity is restored following passage without drug. This silencing process involves generation of small RNA (sRNA) against the target gene via core RNAi pathway proteins. To further elucidate the role of epimutation in the broad antifungal resistance of Mucor, epimutants were isolated that confer resistance to another antifungal agent, 5-fluoroorotic acid (5-FOA). We identified epimutant strains that exhibit resistance to 5-FOA without mutations in PyrF or PyrG, enzymes which convert 5-FOA into the active toxic form. Using sRNA hybridization as well as sRNA library analysis, we demonstrate that these epimutants harbor sRNA against either pyrF or pyrG, and further show that this sRNA is lost after reversion to drug sensitivity. We conclude that epimutation is a mechanism capable of targeting multiple genes, enabling Mucor to develop resistance to a variety of antifungal agents. Elucidation of the role of RNAi in epimutation affords a fuller understanding of mucormycosis. Furthermore, it improves our understanding of fungal pathogenesis and adaptation to stresses, including the evolution of drug resistance. Author Summary The emerging infection mucormycosis causes high mortality in part because the major causative fungi, including Mucor circinelloides, are resistant to most clinically available antifungal drugs. We previously discovered an RNA interference-based resistance mechanism, epimutation, through which M. circinelloides develops transient resistance to the antifungal agent FK506 by altering endogenous RNA expression. We further characterize this novel mechanism by isolating epimutations in two genes that confer resistance to another antifungal agent, 5-fluoroorotic acid. Thus, we demonstrate epimutation can induce resistance to multiple antifungals by targeting a variety of genes. These results reveal epimutation plays a broad role enabling rapid and reversible fungal responses to environmental stresses, including drug exposure, and controlling antifungal drug resistance and RNA expression. As resistance to antifungals emerges, a deeper understanding of the causative mechanisms is crucial for improving treatment.

  • Nanoemulsion as an effective treatment against human-pathogenic fungi
    Alexis Garcia, Yong Yi Fan, Sandeep Vellanki, Eun Young Huh, DiFernando Vanegas, Su He Wang, and Soo Chan Lee
    American Society for Microbiology
    Advances in medicine have resulted in the discovery and implementation of treatments for human disease. While these recent advances have been beneficial, procedures such as solid-organ transplants and cancer treatments have left many patients in an immunocompromised state. Furthermore, the emergence of immunocompromising diseases such as HIV/AIDS or other immunosuppressive medical conditions have opened an opportunity for fungal infections to afflict patients globally. The development of drug resistance in human-pathogenic fungi and the limited array of antifungal drugs has left us in a scenario where we need to develop new therapeutic approaches to treat fungal infections that are less prone to the development of resistance by pathogenic fungi. The significance of our work lies in utilizing a novel nanoemulsion formulation to treat topical fungal infections while minimizing risks of drug resistance development.

  • Rad53-and Chk1-dependent DNA damage response pathways cooperatively promote fungal pathogenesis and modulate antifungal drug susceptibility
    Kwang-Woo Jung, Yeonseon Lee, Eun Young Huh, Soo Chan Lee, Sangyong Lim, and Yong-Sun Bahn
    American Society for Microbiology
    Genome instability is detrimental for living things because it induces genetic disorder diseases and transfers incorrect genome information to descendants. Therefore, living organisms have evolutionarily conserved signaling networks to sense and repair DNA damage. However, how the DNA damage response pathway is regulated for maintaining the genome integrity of fungal pathogens and how this contributes to their pathogenicity remain elusive. In this study, we investigated the DNA damage response pathway in the basidiomycete pathogen Cryptococcus neoformans , which causes life-threatening meningoencephalitis in immunocompromised individuals, with an average of 223,100 infections leading to 181,100 deaths reported annually. Here, we found that perturbation of Rad53- and Chk1-dependent DNA damage response pathways attenuated the virulence of C. neoformans and increased its susceptibility to certain antifungal drugs, such as amphotericin B and flucytosine. Therefore, our work paves the way to understanding the important role of human fungal DNA damage networks in pathogenesis and antifungal drug susceptibility.

  • Genetic Tools for Investigating Mucorales Fungal Pathogenesis
    Alexis Garcia, S. Vellanki and Soo Chan Lee


RECENT SCHOLAR PUBLICATIONS

  • Compositional changes in fecal microbiota associated with clinical phenotypes and prognosis in Korean patients with inflammatory bowel disease
    SY Shin, Y Kim, WS Kim, JM Moon, KM Lee, SA Jung, H Park, EY Huh, ...
    Intestinal research 21 (1), 148-160 2023

  • Identification of mucormycosis by fluorescence in situ hybridization targeting ribosomal RNA in tissue samples
    JJ Dalimot, IMC Smith, J Gerkrath, S Hartmann, OA Cornely, SC Lee, ...
    Journal of Fungi 8 (3), 289 2022

  • Interactions of FK506 and rapamycin with FK506 binding protein 12 in opportunistic human fungal pathogens
    S Vellanki, AE Garcia, SC Lee
    Frontiers in Molecular Biosciences 7, 588913 2020

  • The heterotrimeric G‐protein beta subunit Gpb1 controls hyphal growth under low oxygen conditions through the protein kinase A pathway and is essential for virulence in the
    MI Valle‐Maldonado, JA Patio‐Medina, C Prez‐Arques, ...
    Cellular Microbiology 22 (10), e13236 2020

  • Increased Accumulation of Medium-Chain Fatty Acids by Dynamic Degradation of Long-Chain Fatty Acids in Mucor circinelloides
    SA Hussain, A Garcia, MAK Khan, S Nosheen, Y Zhang, MAG Koffas, ...
    Genes 11 (8), 890 2020

  • Tornadic shear stress induces a transient, calcineurin-dependent hypervirulent phenotype in Mucorales molds
    S Wurster, AM Tatara, ND Albert, AS Ibrahim, J Heitman, SC Lee, ...
    MBio 11 (3), 10.1128/mbio. 01414-20 2020

  • mSphere of influence: the mycobiota in human health and disease
    SC Lee
    Msphere 5 (1), 10.1128/msphere. 00974-19 2020

  • A novel resistance pathway for calcineurin inhibitors in the human-pathogenic mucorales mucor circinelloides
    S Vellanki, RB Billmyre, A Lorenzen, M Campbell, B Turner, EY Huh, ...
    MBio 11 (1), 10.1128/mbio. 02949-19 2020

  • Heterotrimeric G-alpha subunits Gpa11 and Gpa12 define a transduction pathway that control spore size and virulence in Mucor circinelloides
    JA Patio-Medina, NY Reyes-Mares, MI Valle-Maldonado, ...
    PloS One 14 (12), e0226682 2019

  • Nanoemulsion as an effective treatment against human-pathogenic fungi
    A Garcia, YY Fan, S Vellanki, EY Huh, DF Vanegas, SH Wang, SC Lee
    MSphere 4 (6), 10.1128/msphere. 00729-19 2019

  • Epigenetic mechanisms of drug resistance in fungi
    Z Chang, V Yadav, SC Lee, J Heitman
    Fungal Genetics and Biology 132, 103253 2019

  • Calcium-calmodulin-calcineurin signaling: a globally conserved virulence cascade in eukaryotic microbial pathogens
    HS Park, SC Lee, ME Cardenas, J Heitman
    Cell host & microbe 26 (4), 453-462 2019

  • Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents
    PR Juvvadi, D Fox III, BG Bobay, MJ Hoy, SMC Gobeil, RA Venters, ...
    Nature Communications 10 (1), 4275 2019

  • Maternal exercise before and during pregnancy alleviates metabolic dysfunction associated with high-fat diet in pregnant mice, without significant changes in gut microbiota
    E Chung, KA Grue, G Kaur, B Mallory, CR Serrano, SL Ullevig, ...
    Nutrition Research 69, 42-57 2019

  • Gastrointestinal microbiota alteration induced by Mucor circinelloides in a murine model
    KD Mueller, H Zhang, CR Serrano, RB Billmyre, EY Huh, P Wiemann, ...
    Journal of Microbiology 57, 509-520 2019

  • Candida albicans Morphology-Dependent Host FGF-2 Response as a Potential Therapeutic Target
    S Vellanki, EY Huh, SP Saville, SC Lee
    Journal of Fungi 5 (1), 22 2019

  • CRISPR-Cas9 induces point mutation in the mucormycosis fungus Rhizopus delemar
    GO Bruni, K Zhong, SC Lee, P Wang
    Fungal Genetics and Biology 124, 1-7 2019

  • Rad53-and Chk1-dependent DNA damage response pathways cooperatively promote fungal pathogenesis and modulate antifungal drug susceptibility
    KW Jung, Y Lee, EY Huh, SC Lee, S Lim, YS Bahn
    MBio 10 (1), 10.1128/mbio. 01726-18 2019

  • Broad antifungal resistance mediated by RNAi-dependent epimutation in the basal human fungal pathogen Mucor circinelloides
    Z Chang, RB Billmyre, SC Lee, J Heitman
    PLoS genetics 15 (2), e1007957 2019

  • Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents. Nat Commun 10: 4275
    PR Juvvadi, D Fox, BG Bobay, MJ Hoy, SMC Gobeil, RA Venters, ...
    Springer US. doi 2019

MOST CITED SCHOLAR PUBLICATIONS

  • The evolution of sex: a perspective from the fungal kingdom
    SC Lee, M Ni, W Li, C Shertz, J Heitman
    Microbiology and molecular biology reviews 74 (2), 298-340 2010
    Citations: 428

  • Microsporidia evolved from ancestral sexual fungi
    SC Lee, N Corradi, EJ Byrnes, S Torres-Martinez, FS Dietrich, PJ Keeling, ...
    Current Biology 18 (21), 1675-1679 2008
    Citations: 312

  • Signalling pathways in the pathogenesis of Cryptococcus
    L Kozubowski, SC Lee, J Heitman
    Cellular microbiology 11 (3), 370-380 2009
    Citations: 192

  • Expansion of signal transduction pathways in fungi by extensive genome duplication
    LM Corrochano, A Kuo, M Marcet-Houben, S Polaino, A Salamov, ...
    Current Biology 26 (12), 1577-1584 2016
    Citations: 190

  • Calcineurin in fungal virulence and drug resistance: Prospects for harnessing targeted inhibition of calcineurin for an antifungal therapeutic approach
    PR Juvvadi, SC Lee, J Heitman, WJ Steinbach
    Virulence 8 (2), 186-197 2017
    Citations: 189

  • Sporangiospore Size Dimorphism Is Linked to Virulence of Mucor circinelloides
    CH Li, M Cervantes, DJ Springer, T Boekhout, RM Ruiz-Vazquez, ...
    PLoS Pathogens 7 (6), e1002086 2011
    Citations: 184

  • Antifungal drug resistance evoked via RNAi-dependent epimutations
    S Calo, C Shertz-Wall, SC Lee, RJ Bastidas, FE Nicols, JA Granek, ...
    Nature 513 (7519), 555-558 2014
    Citations: 178

  • Calcineurin Plays Key Roles in the Dimorphic Transition and Virulence of the Human Pathogenic Zygomycete Mucor circinelloides
    SC Lee, A Li, S Calo, J Heitman
    PLoS pathogens 9 (9), e1003625 2013
    Citations: 175

  • Calcium-calmodulin-calcineurin signaling: a globally conserved virulence cascade in eukaryotic microbial pathogens
    HS Park, SC Lee, ME Cardenas, J Heitman
    Cell host & microbe 26 (4), 453-462 2019
    Citations: 143

  • Analysis of a Food-Borne Fungal Pathogen Outbreak: Virulence and Genome of a Mucor circinelloides Isolate from Yogurt
    SC Lee, RB Billmyre, A Li, S Carson, SM Sykes, EY Huh, P Mieczkowski, ...
    MBio 5 (4), 10.1128/mbio. 01390-14 2014
    Citations: 139

  • Evolution of the sex-related locus and genomic features shared in microsporidia and fungi
    SC Lee, N Corradi, S Doan, FS Dietrich, PJ Keeling, J Heitman
    PLoS One 5 (5), e10539 2010
    Citations: 106

  • Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents
    PR Juvvadi, D Fox III, BG Bobay, MJ Hoy, SMC Gobeil, RA Venters, ...
    Nature Communications 10 (1), 4275 2019
    Citations: 105

  • Structure, Function, and Phylogeny of the Mating Locus in the Rhizopus oryzae Complex
    AP Gryganskyi, SC Lee, AP Litvintseva, ME Smith, G Bonito, TM Porter, ...
    PLoS One 5 (12), e15273 2010
    Citations: 104

  • Dual action antifungal small molecule modulates multidrug efflux and TOR signaling
    T Shekhar-Guturja, GMKB Gunaherath, EMK Wijeratne, JP Lambert, ...
    Nature chemical biology 12 (10), 867-875 2016
    Citations: 102

  • Human fungal pathogens of Mucorales and Entomophthorales
    L Mendoza, R Vilela, K Voelz, AS Ibrahim, K Voigt, SC Lee
    Cold Spring Harbor perspectives in medicine 5 (4), a019562 2015
    Citations: 98

  • Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host–pathogen interactions of the pathogenic mucoralean fungus Mucor circinelloides
    SC Lee, A Li, S Calo, M Inoue, NK Tonthat, JM Bain, J Louw, ...
    Molecular microbiology 97 (5), 844-865 2015
    Citations: 95

  • Rapamycin Exerts Antifungal Activity In Vitro and In Vivo against Mucor circinelloides via FKBP12-Dependent Inhibition of Tor
    RJ Bastidas, CA Shertz, SC Lee, J Heitman, ME Cardenas
    Eukaryotic cell 11 (3), 270-281 2012
    Citations: 95

  • Broad antifungal resistance mediated by RNAi-dependent epimutation in the basal human fungal pathogen Mucor circinelloides
    Z Chang, RB Billmyre, SC Lee, J Heitman
    PLoS genetics 15 (2), e1007957 2019
    Citations: 76

  • Mucor circinelloides: Growth, Maintenance, and Genetic Manipulation
    S Vellanki, MI Navarro‐Mendoza, A Garcia, L Murcia, C Perez‐Arques, ...
    Current protocols in microbiology 49 (1), e53 2018
    Citations: 69

  • A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides
    S Calo, FE Nicols, SC Lee, A Vila, M Cervantes, S Torres-Martinez, ...
    PLoS Genetics 13 (3), e1006686 2017
    Citations: 66