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, Hyo Jin Kim Heliyon, 2024 Probiotics have been applied to a wide range of bacteria, causing gastrointestinal and vaginal infections. However, probiotics generally possess limited antimicrobial spectra and are primarily utilized as dietary supplements. Recognizing the need for more versatile probiotics, this study focuses on isolating and characterizing strains suitable for antibiotic replacement. Among these strains, Weissella sp. SNUL2, derived from a traditional fermented food in Korea (i.e., Sikhae), emerged as a promising candidate. The correlation between optical density at 600 nm and colony-forming units was verified and applied in subsequent experiments. To assess the therapeutic potential of probiotics, antibacterial tests were conducted using a microplate reader to evaluate the inhibition of 60 bacterial strains (including common foodborne pathogens) induced by Weissella sp. SNUL2 cell-free supernatant (CFS). The results confirmed its broad-spectrum antibacterial properties compared to previously known probiotics. Furthermore, enzymatic treatment with proteinases (trypsin and pepsin) and a time-kill assay were conducted to elucidate the nature of the antibacterial substance in Weissella sp. SNUL2 CFS. Through sequential chromatography involving gel filtration and ion-exchange chromatography, specific fractions with enhanced antibacterial properties were identified. LC-MS/MS analysis of the secretome fraction revealed the presence of various proteins from the C39 family, peptidoglycan endopeptidases, and N-acetylmuramoyl-l-alanine amidase domain-containing protein precursors. Hence, the combined action of these proteins may contribute to Weissella sp. SNUL2's broad antimicrobial activity.
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, Soo Chan Lee, Víctor Meza-Carmen Journal of Microbiology, 2023 Mucormycosis is a lethal and difficult-to-treat fungal infection caused by fungi of the order Mucorales. Mucor lusitanicus, a member of Mucorales, is commonly used as a model to understand disease pathogenesis. However, transcriptional control of hyphal growth and virulence in Mucorales is poorly understood. This study aimed to investigate the role of Tec proteins, which belong to the TEA/ATTS transcription factor family, in the hyphal development and virulence of M. lusitanicus. Unlike in the genome of Ascomycetes and Basidiomycetes, which have a single Tec homologue, in the genome of Mucorales, two Tec homologues, Tec1 and Tec2, were found, except in that of Phycomyces blakesleeanus, with only one Tec homologue. tec1 and tec2 overexpression in M. lusitanicus increased mycelial growth, mitochondrial content and activity, expression of the rhizoferrin synthetase-encoding gene rfs, and virulence in nematodes and wax moth larvae but decreased cAMP levels and protein kinase A (PKA) activity. Furthermore, tec1- and tec2-overexpressing strains required adequate mitochondrial metabolism to promote the virulent phenotype. The heterotrimeric G beta subunit 1-encoding gene deletant strain (Δgpb1) increased cAMP-PKA activity, downregulation of both tec genes, decreased both virulence and hyphal development, but tec1 and tec2 overexpression restored these defects. Overexpression of allele-mutated variants of Tec1(S332A) and Tec2(S168A) in the putative phosphorylation sites for PKA increased both virulence and hyphal growth of Δgpb1. These findings suggest that Tec homologues promote mycelial development and virulence by enhancing mitochondrial metabolism and rhizoferrin accumulation, providing new information for the rational control of the virulent phenotype of M. lusitanicus.
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, Chang Hwan Choi, and Intestinal Research, 2023 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, Soo Chan Lee Plos Pathogens, 2022 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, Volker Rickerts Journal of Fungi, 2022 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, Soo Chan Lee Frontiers in Molecular Biosciences, 2020 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.
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, Blake C. Barrington, Joshua D. Wheaton, Maria Ciofani, Michael Trzoss, Xiaoming Li, Soo Chan Lee, Ying-Lien Chen, Mitchell Mutz, Leonard D. Spicer, Maria A. Schumacher, Joseph Heitman, William J. Steinbach Nature Communications, 2019
An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease Liuyang Wang, Kelly J. Pittman, Jeffrey R. Barker, Raul E. Salinas, Ian B. Stanaway, Graham D. Williams, Robert J. Carroll, Tom Balmat, Andy Ingham, Anusha M. Gopalakrishnan, Kyle D. Gibbs, Alejandro L. Antonia, Joseph Heitman, Soo Chan Lee, Gail P. Jarvik, Joshua C. Denny, Stacy M. Horner, Mark R. DeLong, Raphael H. Valdivia, David R. Crosslin, Dennis C. Ko Cell Host and Microbe, 2018
Dual action antifungal small molecule modulates multidrug efflux and TOR signaling Tanvi Shekhar-Guturja, G. Gunaherath, E. Wijeratne, Jean-Philippe Lambert, A. Averette, Soo Chan Lee, Taeyup Kim, Y. Bahn, F. Tripodi, R. Ammar, Katja Döhl, K. Niewola-Staszkowska, L. Schmitt, R. Loewith, F. Roth, D. Sanglard, D. Andes, C. Nislow, P. Coccetti, A. Gingras, J. Heitman, A. Gunatilaka, L. Cowen Nature Chemical Biology, 2016
Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication L. Corrochano, A. Kuo, M. Marcet-Houben, Silvia Polaino, A. Salamov, J. M. Villalobos-Escobedo, J. Grimwood, M. Álvarez, J. Avalos, Diane Bauer, E. P. Benito, I. Benoit, G. Burger, Lola P Camino, D. Cánovas, E. Cerdá-Olmedo, Jan-Fang Cheng, A. Dominguez, M. Eliáš, A. P. Eslava, F. Glaser, G. Gutiérrez, J. Heitman, B. Henrissat, E. A. Iturriaga, B. Lang, J. L. Lavín, Soo Chan Lee, Wenjun Li, E. Lindquist, S. López-García, Eva M. Luque, A. T. Marcos, Joel A. Martin, K. McCluskey, H. Medina, A. Miralles-Durán, A. Miyazaki, E. Muñoz-Torres, J. A. Oguiza, R. Ohm, M. Olmedo, M. Orejas, L. Ortiz-Castellanos, A. Pisabarro, J. Rodríguez-Romero, J. Ruiz-Herrera, R. Ruiz-Vazquez, Catalina Sanz, W. Schackwitz, M. Shahriari, E. Shelest, Fatima Silva-Franco, D. Soanes, K. Syed, V. G. Tagua, N. Talbot, M. Thon, H. Tice, R. D. Vries, A. Wiebenga, J. Yadav, E. Braun, S. Baker, V. Garre, J. Schmutz, B. Horwitz, S. Torres-Martínez, A. Idnurm, A. Herrera‐Estrella, T. Gabaldón, I. Grigoriev Current Biology, 2016
Sex and the Microsporidia Soo Chan Lee, Joseph Heitman, Joseph E. Ironside Microsporidia Pathogens of Opportunity First Edition, 2014
Antifungal drug resistance evoked via RNAi-dependent epimutations Silvia Calo, Cecelia Shertz-Wall, Soo Chan Lee, Robert J. Bastidas, Francisco E. Nicolás, Joshua A. Granek, Piotr Mieczkowski, Santiago Torres-Martínez, Rosa M. Ruiz-Vázquez, Maria E. Cardenas, Joseph Heitman Nature, 2014
Microsporidia Evolved from Ancestral Sexual Fungi Soo Chan Lee, Nicolas Corradi, Edmond J. Byrnes, Santiago Torres-Martinez, Fred S. Dietrich, Patrick J. Keeling, Joseph Heitman Current Biology, 2008
Effect of arsA, arsenite-specific ATPase, on inhibition of cell division in Escherichia coli Journal of Microbiology and Biotechnology, 2001
RECENT SCHOLAR PUBLICATIONS
Microbial links to Alzheimer’s disease CP Cornitius, EK Perez, SC Lee PLoS Pathogens 21 (10), e1013599 , 2025 2025 Citations: 1
Author Correction: 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 16, 6129 , 2025 2025 Citations: 2
Weissella sp. SNUL2 as potential probiotics with broad-spectrum antimicrobial activities JW Han, N Lee, HJ Kim, SJ Moon, SC Lee, HJ Kim Heliyon 10 (7) , 2024 2024 Citations: 4
The amino acid permease Byc1 is involved in calcineurin-dependent thermos-tolerance in Cryptococcus neoformans KT Lee, M Giner, D Bahn, CP Cornitius, SC Lee bioRxiv, 2024.02. 27.582329 , 2024 2024
Transcription Factors Tec1 and Tec2 Play Key Roles in the Hyphal Growth and Virulence of Mucor lusitanicus Through Increased Mitochondrial Oxidative Metabolism V Alejandre-Castañeda, JA Patiño-Medina, MI Valle-Maldonado, A García, ... Journal of Microbiology 61 (12), 1043-1062 , 2023 2023 Citations: 7
Dimorphism and Pathogenesis in Mucor Species A Garcia, CP Smith, SC Lee Evolution of Fungi and Fungal-Like Organisms, 93-101 , 2023 2023 Citations: 4
Serine/threonine phosphatase calcineurin orchestrates the intrinsic resistance to micafungin in the human-pathogenic fungus Mucor circinelloides A Garcia, EY Huh, SC Lee Antimicrobial Agents and Chemotherapy 67 (2), e00686-22 , 2023 2023 Citations: 9
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 2023 Citations: 28
Current treatments against mucormycosis and future directions C Smith, SC Lee PLoS Pathogens 18 (10), e1010858 , 2022 2022 Citations: 90
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 2022 Citations: 8
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 2020 Citations: 18
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 Patiño‐Medina, C Pérez‐Arques, ... Cellular Microbiology 22 (10), e13236 , 2020 2020 Citations: 23
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 2020 Citations: 21
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 2020 Citations: 19
mSphere of influence: the mycobiota in human health and disease SC Lee Msphere 5 (1), 10.1128/msphere. 00974-19 , 2020 2020 Citations: 7
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 2020 Citations: 45
Heterotrimeric G-alpha subunits Gpa11 and Gpa12 define a transduction pathway that control spore size and virulence in Mucor circinelloides JA Patiño-Medina, NY Reyes-Mares, MI Valle-Maldonado, ... PloS One 14 (12), e0226682 , 2019 2019 Citations: 14
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 2019 Citations: 30
Epigenetic mechanisms of drug resistance in fungi Z Chang, V Yadav, SC Lee, J Heitman Fungal Genetics and Biology 132, 103253 , 2019 2019 Citations: 82
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 2019 Citations: 190
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 2010 Citations: 456
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 2008 Citations: 320
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 2017 Citations: 214
Signalling pathways in the pathogenesis of Cryptococcus L Kozubowski, SC Lee, J Heitman Cellular microbiology 11 (3), 370-380 , 2009 2009 Citations: 202
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 2016 Citations: 200
Antifungal drug resistance evoked via RNAi-dependent epimutations S Calo, C Shertz-Wall, SC Lee, RJ Bastidas, FE Nicolás, JA Granek, ... Nature 513 (7519), 555-558 , 2014 2014 Citations: 197
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 2013 Citations: 194
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 2011 Citations: 191
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 2019 Citations: 190
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 2014 Citations: 151
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 2019 Citations: 132
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 2016 Citations: 119
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 2015 Citations: 110
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 2010 Citations: 108
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 2012 Citations: 104
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 2010 Citations: 104
Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host–pathogen interactions of the pathogenic mucoralean fungus M ucor circinelloides SC Lee, A Li, S Calo, M Inoue, NK Tonthat, JM Bain, J Louw, ... Molecular microbiology 97 (5), 844-865 , 2015 2015 Citations: 103
Current treatments against mucormycosis and future directions C Smith, SC Lee PLoS Pathogens 18 (10), e1010858 , 2022 2022 Citations: 90
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 2019 Citations: 84
Epigenetic mechanisms of drug resistance in fungi Z Chang, V Yadav, SC Lee, J Heitman Fungal Genetics and Biology 132, 103253 , 2019 2019 Citations: 82