About

Dr. Bettina Fries is a Professor of Medicine and Microbiology with a focus on infectious diseases. Her research encompasses a broad range of topics including the characterization of pathogenic fungi such as Cryptococcus neoformans, the phenotypic switching and virulence mechanisms of fungi, and the immune response to fungal infections. She has contributed significantly to understanding how phenotypic variations influence virulence, pathogenesis, and host immune responses, particularly in the context of cryptococcal infections. Her work also involves studying bacterial toxins, monoclonal antibody therapies, and biofilm formation in clinical isolates, aiming to develop better diagnostic, therapeutic, and preventive strategies against infectious diseases.

Research topics

• Medicine
• Biology
• Internal medicine
• Environmental health
• Microbiology
• Demography
• Emergency medicine
• Virology
• Genetics

Selected publications

• Resistance to novel β-lactam/β-lactamase inhibitors among carbapenem-resistant <i>Pseudomonas aeruginosa</i> and clinical implications in the prospective observational <i>Pseudomonas</i> study

  Antimicrobial Agents and Chemotherapy · 2026-05-15

  articleOpen access

  ABSTRACT Novel β-lactam/β-lactamase inhibitors (βL/βLIs) are important therapies for carbapenem-resistant Pseudomonas aeruginosa (CRPA). However, the global extent of resistance to these agents and the impact of resistance on patient outcomes are unclear. We therefore evaluated patients with CRPA isolates at 35 hospitals (nine countries) from December 2018 to November 2019. Antimicrobial susceptibility testing was performed at a central laboratory by agar dilution for ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) and by broth microdilution for imipenem-relebactam (I/R). Characteristics and outcomes, including desirability of outcome rankings (DOOR), were compared between patients infected with isolates not susceptible vs susceptible to each agent. Of 800 CRPA isolates, susceptibility to C/T, CZA, and I/R was 69%, 67%, and 33%, respectively. USA isolates ( n = 526) were more frequently susceptible to these agents than isolates from other countries ( n = 274; C/T: 83% vs 42%; CZA: 77% vs 47%; I/R: 37% vs 23%; P &lt; 0.001 for each comparison) and isolates with carbapenemases ( n = 157) were less frequently susceptible than isolates without carbapenemases ( n = 643; C/T: 7% vs 84%; CZA: 24% vs 77%; I/R: 6% vs 39%; P &lt; 0.001 for each comparison). Thirty-day mortality and DOOR were similar overall in patients infected with isolates not susceptible vs susceptible to each βL/βLI. However, the adjusted probability of a better DOOR outcome for a randomly selected patient with bacteremia due to a C/T-not susceptible vs -susceptible isolate was 38.2% (95% confidence interval, 25.6%–52.7%). Resistance to novel βL/βLIs, especially I/R, is common in CRPA, particularly outside the USA and in carbapenemase-producing isolates. Additional treatment options are needed for CRPA infections.

  PublisherDOI

• Carbapenem-resistant Enterobacterales in solid organ transplant recipients

  UNC Libraries · 2026-04-02

  articleOpen access
  PublisherDOI

• Molecular Epidemiology and Clinical Characterization of Carbapenemase-Producing Enterobacter Species From an International Cohort.

  Carolina Digital Repository (University of North Carolina at Chapel Hill) · 2025-06-15

  article

  Despite the global public health threat posed by carbapenem-resistant Enterobacter spp, clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp infections.Hospitalized patients enrolled in the CRACKLE-2 study (ClinicalTrials.gov, NCT03646227) from 2016 to 2018 with cultures positive for carbapenemase-producing Enterobacter spp were included. Clinical and microbiologic data were collected from health records. Whole genome sequencing was performed, and the population structures of selected predominant clones were analyzed.We enrolled 136 hospitalized patients with carbapenemase-producing Enterobacter spp from 30 hospitals in 7 countries. Among the 136 isolates, 11 Enterobacter spp were identified, with most isolates belonging to E xiangfangensis (n = 81 [60%]) and E hoffmannii (n = 17 [13%]) and carrying blaKPC (n = 106 [78%]) and blaNDM (n = 12 [9%]). Clinical characteristics and outcomes were similar among patients with E xiangfangensis, E hoffmannii, or the other Enterobacter spp. Thirty-day mortality was 20%, and older age at enrollment (adjusted odds ratio, 1.42 [95% confidence interval, 1.08-1.87]) was associated with increased mortality. Sequence type (ST) 171 E xiangfangensis, ST78 E hoffmannii, and ST93 E xiangfangensis were the predominant clones, and the acquisition of fluoroquinolone resistance-associated mutations and carbapenemase-encoding plasmids contributed to their formation and global dissemination.Our findings demonstrate that E xiangfangensis and E hoffmannii are common species among international carbapenemase-producing Enterobacter spp, potentially linked to the clonal spread of a few predominant clones that have acquired fluoroquinolone resistance and carbapenemase-encoding plasmids.

  Publisher

• Evaluating size exclusion chromatography for nucleic acid removal in Klebsiella pneumoniae cell surface polysaccharide purification

  Carbohydrate Polymers · 2025-03-24 · 1 citations

  articleOpen accessSenior author

  H 1D-NMR and 2D-NMR demonstrate that the cell surface-associated polysaccharide purified with this study is highly homogeneous and identified as antigenic O-polysaccharide. This approach streamlines the purification process by eliminating the need for nuclease digestion and additional ethanol precipitation steps.

  PublisherDOI

• Chemical Synthesis of <i>Pseudomonas aeruginosa</i> , <i>Staphylococcus aureus</i> , and <i>Acinetobacter baumannii</i> Capsular Polysaccharide Fragments as Leads for Cross‐Protection

  Angewandte Chemie International Edition · 2025-12-21 · 2 citations

  articleOpen access

  Pseudomonas aeruginosa and Staphylococcus aureus are listed by the World Health Organization as high-priority multidrug-resistant (MDR) pathogens, whereas Acinetobacter baumannii is classified as the critical-priority group. These bacteria cause life-threatening infections such as severe bloodstream, nosocomial, urinary tract, and soft-tissue infections. Their cell surfaces display complex and structurally distinct glycans absent in host cells, making them targets for glycoconjugate vaccine and diagnostic research. In this study, we report the chemical synthesis of mono- and oligosaccharide fragments derived from three ESKAPE pathogens, P. aeruginosa O11, S. aureus (CP5, CP8, and strain M), and A. baumannii (S34 and O5), as well as Plesiomonas shigelloides O1. Glycan microarray screening revealed three epitopes exhibiting strong cross-reactive immunogenicity against P. aeruginosa, S. aureus, and A. baumannii, demonstrating that a trisaccharide represents the minimal epitope required to elicit cross-protective immune responses. The key features of P. aeruginosa O11 trisaccharide synthesis involve efficient assembly of a 1,2-cis-linked l-FucNAc-linker motif, followed by regioselective glycosylation at O3 and subsequently at O2 of the d-Glc-l-FucNAc-linker disaccharide. The same strategy was applied for assembling its tetrasaccharide fragment. Additionally, β-mannosylation and 1,2-cis-d-FucNAc linkage formations were optimized for the S. aureus CP8 fragment, establishing a versatile route toward bacterial glycans relevant for vaccine and diagnostic development.

  PublisherOA PDFDOI

• Chemical Synthesis of <i>Pseudomonas aeruginosa</i> , <i>Staphylococcus aureus</i> , and <i>Acinetobacter baumannii</i> Capsular Polysaccharide Fragments as Leads for Cross‐Protection

  Angewandte Chemie · 2025-12-21 · 1 citations

  articleOpen access

  Abstract Pseudomonas aeruginosa and Staphylococcus aureus are listed by the World Health Organization as high‐priority multidrug‐resistant (MDR) pathogens, whereas Acinetobacter baumannii is classified as the critical‐priority group. These bacteria cause life‐threatening infections such as severe bloodstream, nosocomial, urinary tract, and soft‐tissue infections. Their cell surfaces display complex and structurally distinct glycans absent in host cells, making them targets for glycoconjugate vaccine and diagnostic research. In this study, we report the chemical synthesis of mono‐ and oligosaccharide fragments derived from three ESKAPE pathogens, P. aeruginosa O11, S. aureus (CP5, CP8, and strain M), and A. baumannii (S34 and O5), as well as Plesiomonas shigelloides O1. Glycan microarray screening revealed three epitopes exhibiting strong cross‐reactive immunogenicity against P. aeruginosa , S. aureus , and A. baumannii , demonstrating that a trisaccharide represents the minimal epitope required to elicit cross‐protective immune responses. The key features of P. aeruginosa O11 trisaccharide synthesis involve efficient assembly of a 1,2‐ cis ‐linked l ‐FucNAc–linker motif, followed by regioselective glycosylation at O3 and subsequently at O2 of the d ‐Glc– l ‐FucNAc–linker disaccharide. The same strategy was applied for assembling its tetrasaccharide fragment. Additionally, β ‐mannosylation and 1,2‐ cis ‐ d ‐FucNAc linkage formations were optimized for the S. aureus CP8 fragment, establishing a versatile route toward bacterial glycans relevant for vaccine and diagnostic development.

  PublisherDOI

• Host–Pathogen Interactions and Correlated Factors That Are Affected in Replicative-Aged Cryptococcus neoformans

  Journal of Fungi · 2024-04-10

  articleOpen accessSenior authorCorresponding

  Cryptococcus neoformans is a facultative intracellular fungal pathogen. Ten-generation-old (10GEN) C. neoformans cells are more resistant to phagocytosis and killing by macrophages than younger daughter cells. However, mechanisms that mediate this resistance and intracellular parasitism are poorly understood. Here, we identified important factors for the intracellular survival of 10GEN C. neoformans, such as urease activity, capsule synthesis, and DNA content using flow cytometry and fluorescent microscopy techniques. The real-time visualization of time-lapse imaging was applied to determine the phagosomal acidity, membrane permeability, and vomocytosis (non-lytic exocytosis) rate in J774 macrophages that phagocytosed C. neoformans of different generational ages. Our results showed that old C. neoformans exhibited higher urease activity and enhanced Golgi activity. In addition, old C. neoformans were more likely to be arrested in the G2 phase, resulting in the occasional formation of aberrant trimera-like cells. To finish, the advanced generational age of the yeast cells slightly reduced vomocytosis events within host cells, which might be associated with increased phagolysosome pH and membrane permeability. Altogether, our results suggest that old C. neoformans prevail within acidic phagolysosomes and can manipulate the phagosome pH. These strategies may be used by old C. neoformans to resist phagosomal killing and drive cryptococcosis pathogenesis. The comprehension of these essential host–pathogen interactions could further shed light on mechanisms that bring new insights for novel antifungal therapeutic design.

  PublisherOA PDFDOI

• Distinct effect of calorie restriction between congenic mating types of Cryptococcus neoformans

  Scientific Reports · 2024-08-06 · 1 citations

  articleOpen accessSenior author

  Cryptococcus neoformans (Cn) is an opportunistic yeast that causes meningoencephalitis in immunocompromised individuals. Calorie restriction (CR) prolongs Cn replicative lifespan (RLS) and mimics low-glucose environments in which Cn resides during infection. The effects of CR-mediated stress can differ among strains and have only been studied in MATα cells. Cn replicates sexually, generating two mating types, MATα and MATa. MATα strains are more dominant in clinical and environmental isolates. We sought to compare the effects of CR stress and longevity regulation between congenic MATα and MATa. Although MATα and MATa cells extended their RLS in response to CR, they engaged different pathways. The sirtuins were upregulated in MATα cells under CR, but not in MATa cells. RLS extension was SIR2-dependent in KN99α, but not in KN99a. The TOR nutrient-sensing pathway was downregulated in MATa strains under CR, while MATα strains demonstrated no difference. Lower oxidative stress and higher ATP production were observed in KN99α cells, possibly due to higher SOD expression. SIR2 was important for mitochondrial morphology and function in both mating types. Increased ATP production during CR powered the upregulated ABC transporters, increasing efflux in MATα cells. This led to enhanced fluconazole tolerance, while MATa cells remained sensitive to fluconazole. Our investigation highlights differences in the response of the mating types to CR.

  PublisherOA PDFDOI

• <i>Klebsiella pneumoniae</i> Glycoconjugate Vaccine Leads Based on Semi‐Synthetic O1 and O2ac Antigens

  Angewandte Chemie International Edition · 2024-12-27 · 4 citations

  articleOpen access

  Klebsiella pneumoniae (KP) is a common opportunistic pathogen that emerged as a new critical threat to human health, due to its hypervirulence and widespread resistance against many antibiotics, including carbapenems. Alternative intervention strategies such as vaccines are not available. Cell-surface lipopolysaccharides (LPS) and capsular polysaccharides (CPS) are attractive targets for vaccine development. We present a method to synthesize LPS substructures, covering over 70 % of virulent KP strains that were used to characterize the antibody repertoire of infected patients. Thereby, glycoconjugate vaccine leads against the Klebsiella pneumoniae serotypes O1, O2a, O2afg and O2ac have been identified.

  PublisherOA PDFDOI

• Carbapenem-resistant Enterobacterales in Children at 18 US Health Care System Study Sites: Clinical and Molecular Epidemiology From a Prospective Multicenter Cohort Study

  UNC Libraries · 2024-10-22

  articleOpen access

  Background: Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat in the United States. Objective: Describe the clinical and molecular epidemiology of CRE in a multicenter pediatric cohort. Methods: CRACKLE-1 and CRACKLE-2 are prospective cohort studies with consecutive enrollment of hospitalized patients with CRE infection or colonization between 24 December 2011 and 31 August 2017. Patients younger than age 18 years and enrolled in the CRACKLE studies were included in this analysis. Clinical data were obtained from the electronic health record. Carbapenemase genes were detected using polymerase chain reaction and whole-genome sequencing. Results: Fifty-one children were identified at 18 healthcare system study sites representing all U.S. census regions. The median age was 8 months, with 67% younger than age 2 years. Median number of days from admission to culture collection was 11. Seventy-three percent of patients had required intensive care and 41% had a history of mechanical ventilation. More than half of children had no documented comorbidities (Q1, Q3 0, 2). Sixty-seven percent previously received antibiotics during their hospitalization. The most common species isolated were Enterobacter species (41%), Klebsiella pneumoniae (27%), and Escherichia coli (20%). Carbapenemase genes were detected in 29% of isolates tested, which was lower than previously described in adults from this cohort (61%). Thirty-four patients were empirically treated on the date of culture collection, but only 6 received an antibiotic to which the CRE isolate was confirmed susceptible in vitro. Thirty-day mortality was 13.7%. Conclusions: CRE infection or colonization in U.S. children was geographically widespread, predominantly affected children younger than age 2 years, associated with significant mortality, and less commonly caused by carbapenemase-producing strains than in adults.

  PublisherDOI

Recent grants

• Development of antibodies to capsule of carbapenem resistant Klebsiella pneumonia

  NIH · $435k · 2014–2017

• Optimization of therapeutic mAbs to carbapenem resistant Klebsiella clone ST258

  NIH · 2019–2027

• NIH Grant R21AI087564

  NIH · $454k · 2013

• NIH Grant K08AI001570

  NIH · $574k · 2004

• Host Response to Phenotypic Switch Variant of C. Neoformans

  NIH · $3.6M · 2014–2016

Frequent coauthors

• Natália Kronbauer Oliveira

  Stony Brook University

  45 shared

• Robert A. Bonomo

  University School

  43 shared

• César A. Arias

  Universidad El Bosque

  42 shared

• Michael J. Satlin

  Weill Cornell Medicine

  39 shared

• Liang Chen

  38 shared

• Somanon Bhattacharya

  32 shared

• Tejas Bouklas

  University of California, Los Angeles

  30 shared

• Carol Hill

  Clinical Research Institute

  29 shared

Education

• medical doctor

  Albert-Ludwigs-Universität Freiburg

  1991