Bettina Fries

E-mail:
Office:
Fax:

Bettina.Fries@stonybrookmedicine.edu
(631) 638-7948
(631) 444-7518

Research

The Fries laboratory investigates questions related to fungal pathogenesis and antibody biology. My laboratory’s research contributes to our current understanding of how C. neoformans changes during chronic infection. We investigated phenotypic switching in C. neoformans and have identified ALL1, a gene regulated by phenotypic switching, that affects viscosity and length of the cryptococcal polysaccharide. More recently my group has worked on replicative aging in fungi. We showed in several pathogenic fungi that aging leads to antifungal and anti-phagocytic resistance and that this resilient phenotype is selected during chronic infection. The concept that aging promotes heterogeneity in fungal pathogen populations is novel and relevant also for Candida glabrata and Candida auris, where aging leads to remodeling of the fungal cell wall and changes in ergosterol pathway and efflux pump activity.  Our research is conceptually innovative. My group was the first to show that replicative aging generates heterogeneity in Cryptococcus neoformans, in Candida glabrata and Candida auriis populations and leads to a resilient phenotype through remodeling of the cell wall. Older cells persist because they resist the host immune response and killing by antifungals. Our antibody research focuses on developing novel therapies for multi-drug resistant bacteria. Currently we are focusing on developing monoclonal antibodies to the polysaccharide capsule of carbapenem resistant Klebsiella. This pathogen is classified as a top priority MDR pathogen by WHO and NIAID because this bacterium is one of the most common multi-drug resistant bacteria isolated from infected patients. The polysaccharide capsule is very heterogeneous and in addition to developing monoclonal antibodies we are hoping also to identify cross-reactive epitopes that can be used as lead vaccine targets. We have made major contributions to basic knowledge of antibody biology as well. We have showed that isotype switch variants differ in their protective efficacy. We have demonstrated that a combination of non-protective mAbs can enhance efficacy by inducing subtle allosteric conformational changes in Staphylococcal enterotoxin B that perturbed formation of the SEB·T-cell receptor MHC class II trimer.

Selected Publications:

1. N. Jain, R. J.B. Cordero, A. Casadevall and B. C. Fries. Allergen1 Regulates Polysaccharide Structure in Cryptococcus neoformans. Mol Microbiol. 2013 Apr 9. doi: 10.1111/mmi.12216. [Epub ahead of print] PMID: 23565821
2. T. Bouklas, X. Pechuan, D. L. Goldman, B. Edelman, A. Bergman, and B. C. Fries. Old Cryptococcus neoformans Cells Contribute to Virulence in Chronic Cryptococcosis Mbio 2013 Aug 13;4(4) Aug 13;4(4). pii: e00455-13. PMID: 23943761
3. N. Jain, Bouklas T, Gupta A, Varshney AK, Orner EP, Fries BC. ALL2, a Homologue of ALL1, Has a Distinct Role in Regulating pH Homeostasis in the Pathogen Cryptococcus neoformans. Infect Immun. 2015 Nov 23;84(2):439-51 PMID: 26597983 :713-27
4. T. Bouklas, Alonso-Crisóstomo L, Székely T Jr, Diago-Navarro E, Orner EP, Smith K, Munshi MA, Del Poeta M, Balázsi G, Fries BC. "Generational Distribution of a Candida glabrata Population:  Resilient Old Cells Prevail, while Younger Cells Dominate in the Vulnerable Host" accepted in PLOS pathogen 2017 May 10;13(5):e1006355. doi: 10.1371 PMID: 28489916
5. S. Bhattacharya S, Fries BC. Enhanced Efflux Pump Activity in Old Candida glabrata.  Antimicrob Agents Chemother. 2018 Jan 8. pii: AAC.02227-17. doi: 10.1128/AAC.02227-17. [Epub ahead of print] PMID: 29311061
6. Diago-Navarro E, Motley MP, Ruiz-Perez G, Yu W, Austin J, Seco BMS, Xiao G, Chikhalya A, Seeberger PH, Fries BC. Novel, broadly reactive Anti-capsular Antibodies against Carbapenem -resistant Klebsiella Pneumoniae protect from Infection, MBio. 2018 Apr 3;9(2).
7. Bhattacharya S, Holowka T, Orner EP, Fries BC. Gene Duplication Associated with Increased Fluconazole Tolerance in Candida auris cells of Advanced Generational Age. Sci Rep. 2019 Mar 25;9(1):5052
8. E. Diago-Navarro E1, Calatayud-Baselga I, Sun D3, Khairallah C, Mann I, Ulacia-Hernando A, Sheridan B, Shi M, Fries BC. Antibody based immunotherapy to treat and prevent infection with hypervirulent Klebsiella pneumoniae. Clin Vaccine Immunol. 2016 Oct 26. Epup ahead of print PMID: 27795303
9. T. Bouklas, Jain N, Fries BC. Modulation of Replicative Lifespan in Cryptococcus neoformans: Implications for Virulence. Front Microbiol. 2017 Jan 30;8:98. PMID: 28194146
10. T. Bouklas, Alonso-Crisóstomo L, Székely T Jr, Diago-Navarro E, Orner EP, Smith K, Munshi MA, Del Poeta M, Balázsi G, Fries BC. "Generational Distribution of a Candida glabrata Population:  Resilient Old Cells Prevail, while Younger Cells Dominate in the Vulnerable Host" accepted in PLOS pathogen 2017 May 10;13(5):e1006355. doi: 10.1371 PMID: 28489916
11. Diago-Navarro E, Motley MP, Ruiz-Perez G, Yu W, Austin J, Seco BMS, Xiao G, Chikhalya A, Seeberger PH, Fries BC. Novel, broadly reactive Anti-capsular Antibodies against Carbapenem -resistant Klebsiella Pneumoniae protect from Infection, MBio. 2018 Apr 3;9(2). pii: e00091-18. doi: 10.1128/mBio.00091-18. Erratum in: MBio. 2018 Jun 12;9(3): PMID: 29615497
12. Bouklas T, Masone L, Fries BC. Differences in Sirtuin Regulation in Response to Calorie Restriction in Cryptococcus neoformans. J Fungi (Basel). 2018 Feb 18;4(1). pii: E26. doi: 10.3390/jof4010026. PMID:29463010
13. Orner EP, Zhang P, Jo M, Bhattacharya S , Qin  L. , Fries, B C. High-Throughput Yeast Aging Analysis for Cryptococcus (HYAAC) microfluidic device streamlines aging studies in Cryptococcus neoformans accepted Commun Biol. 2019 Jul 10;2:256. doi: 10.1038/s42003-019-0504-5. eCollection 2019.PMID: 31312725
14. Orner EP, Bhattacharya S, Kalenja K, Hayden D, Del Poeta M, Fries BC. Cell Wall-Associated Virulence Factors Contribute to Increased Resilience of Old Cryptococcus neoformans Cells. Front Microbiol. 2019 Nov 7;10:2513. doi: 10.3389/fmicb.2019.02513. eCollection 2019.PMID: 31787940
15. Motley MP, Diago-Navarro E, Banerjee K, Inzerillo S, Fries BC. The Role of IgG Subclass in Antibody-Mediated Protection against Carbapenem-Resistant Klebsiella pneumoniae. mBio. 2020 Sep 8;11(5):e02059-20. doi: 10.1128/mBio.02059-20.PMID: 32900809

Kasturi Banerjee, PhD
Somanon Bhattacharya, PhD
Vanessa Karina Alves Da Silva, PhD

Natalia Kronbauer de Oliveira, Graduate Student
Michael Motley, MSTP Student (completed PhD)