Mark Brynildsen
Princeton University, NJ·Microbiology & Immunology
Bacteria often survive conditions that should kill them. This lab studies how stressed bacteria survive, with a focus on two situations.
- Fields
Microbiology & Immunology
Engineering
Biology
- Topics
antibiotic persisters
persistence
antibiotic tolerance
- Grants
- 3 known grants, through Jan 2029
What they work on
- Identify the DNA repair systems that single- and double-chromosome E. coli persisters use to survive fluoroquinolones such as ciprofloxacin, by sorting cells by chromosome number with FACS and testing DNA repair mutants.
- Test whether chromosome copy number affects E. coli killing by other antibiotics, including nitrofurantoin, trimethoprim-sulfamethoxazole and rifaximin, using lab and urinary tract infection isolates.
- Screen an FDA-approved repurposing library and a diverse small-molecule library with Hoechst staining and high-throughput flow cytometry for compounds that increase single-chromosome cells.
- Measure whether fluoroquinolone persistence in Pseudomonas aeruginosa depends on chromosome number, by counting chromosomes with stains and a fluorescent origin reporter and sorting cells with FACS.
- Determine the roles of homologous recombination, NHEJ and other genes in P. aeruginosa persisters with different chromosome numbers, using genetic mutants and Tn-seq on sorted populations.
- Determine how iron-starved E. coli supply iron and reducing power to defend against nitric oxide, and why iron-starved P. aeruginosa cannot, using mutants, synthetic biology, mass spectrometry and systems modeling.
More about the research
The first involves persisters: a small fraction of genetically ordinary cells that tolerate antibiotics without being resistant. Persisters are thought to drive chronic and relapsing infections and can speed the evolution of resistance. The second asks how bacteria starved of iron cope when a second threat, nitric oxide, arrives at the same time. In both cases the projects look at features of individual cells and at how cells allocate limited resources, combining genetics, cell sorting, sequencing, mass spectrometry and modeling.
Why it matters
Persister cells help infections such as urinary tract and Pseudomonas infections come back after treatment and can speed up antibiotic resistance. By revealing how chromosome number and DNA repair shape persister survival, this work could point to new ways to make fluoroquinolones more effective, including drugs that act as ploidy modulators to aid antibiotics. Understanding how iron-starved bacteria withstand nitric oxide could also inform human health and agriculture.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Examining how robustness and paralysis to the same stress manifests in iron-starved bacteria
NSF · Feb 2025 – Jan 2029
Examining the influence of chromosome copy number on Pseudomonas aeruginosa persisters to fluoroquinolones
NIH · Apr 2025 – Mar 2027
Investigating ploidy modulation as a strategy to improve antibiotic activity
NIH · Apr 2024 – Aug 2026
Closest labs
Joshua Heyza
Wayne State University, MI·Biochemistry·Early-career
Determine what the intrinsically disordered PST repeat domain of MDC1 binds on chromatin and how phosphorylation regulates that tether, using molecular, biochemical and biophysical approaches together with live-cell single-molecule imaging.
Mehmet Orman
University of Houston, TX·Microbiology & Immunology·Early-career
Identify genes important for persister colonization using a high-throughput fluorescence-based screen combined with transposon mutagenesis and genomic sequencing.
Francesca Storici
Georgia Institute of Technology, GA·Genetics
Build matched human kidney (HEK293T) and diploid retinal pigment epithelial (RPE-1) cell lines expressing spliced or non-spliced RNA from the same AAVS1 safe-harbor insertion site, and measure how each transcript changes end-joining repair of CRISPR/Cas9 breaks using deep sequencing.
The school
Princeton University: 26 labs on PI Pages, $559M a year on research, 403 research doctorates a year.
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