Center for Molecular Medicine Cologne

Maier, Berenike | Higgins, Paul - B 08

Correlating biofilm structure with antibiotic tolerance

Introduction

Aggregation into colonies and biofilms can protect bacteria from antibiotic treatment. Treatment of biofilm-related infections requires a detailed understanding of the molecular mechanisms of antibiotic tolerance. This project aims at understanding how colony formation protects the human pathogen Neisseria gonorrhoeae from antibiotic treatment. We will focus on the interplay between the physical properties of gonococcal colonies and antibiotic susceptibility.

  1. We will study the effect of colony formation and colony fluidity on tolerance.
    To identify molecular mechanisms that confer antibiotic tolerance, we will follow two complementary approaches.
  2. We will investigate how colony formation affects genome-wide gene expression and correlate differential gene expression to tolerance.
  3. We will study the evolution of antibiotic tolerance.
    In the long term, it will be interesting to investigate the interplay between antibiotic tolerance and antibiotic resistance in the gonococcal system.
Figure 1

Clinical Relevance

According to WHO, gonorrhea is currently the second most common STI worldwide. Vaccination is not available and the probability of failure of treatment with antibiotics is rising rapidly (1). Due to its rapid acquisition of antibiotic resistance, (multi-) drug resistant N. gonorrhoeae have been termed an urgent threat by the US Center for Disease Control. Some aspects of drug resistance are understood at the genetic level, but the effect of biofilm formation and its properties on efficiency of treatment remains poorly understood. This project aims at elucidating potential mechanisms of antibiotic tolerance in gonococcal biofilms.

Approach

  • Characterize the role of colony formation on antibiotic tolerance
  • Determine changes in gene expression in response to colony formation and correlate them to antibiotic tolerance
  • Set up laboratory evolution experiment to assess evolution of colony phenotype, tolerance, and resistance
Figure 2

Overview of publications generated during the current funding period (1/2023-12/2025) with CMMC affiliation

For a complete list of B. Meier's publications, please visit - pubmed_Meier
For a complete list of P. Higgins' publications, please visit - pubmed_Higgins

  • Forster M, Rathmann I, Yuksel M, Power JJ, and Maier B (2023). Genome-wide transformation reveals extensive exchange across closely related Bacillus species. Nucleic Acids Res 51, 12352-12366. doi:10.1093/nar/gkad1074.
     
  • Hennes M, Bender N, Cronenberg T, Welker A, and Maier B (2023). Collective polarization dynamics in bacterial colonies signify the occurrence of distinct subpopulations. PLoS Biol 21, e3001960. doi:10.1371/journal.pbio.3001960.
Prof. Dr. Berenike Maier CMMC Cologne
Prof. Dr. Berenike Maier

Institute for Biological Physics - Center for Molecular Biosciences

CMMC - PI - B 08

+49 221 470 8046

Institute for Biological Physics - Center for Molecular Biosciences

Zülpcher Str. 47a

50674 Cologne

https://biophysics.uni-koeln.de/

CMMC Profile Page

Curriculum Vitae (CV)

Publications on PubMed

Dr. Paul Higgins CMMC Cologne
Dr. Paul Higgins

Institute for Medical Microbiology, Immunology and Hygiene

CMMC - Co-PI - B 08

+49 221 478 32011

Institute for Medical Microbiology, Immunology and Hygiene

Goldenfelsstraße 19-21

50935 Cologne

http://immih.uk-koeln.de/forschung/ag-higgins

CMMC Profile Page

Curriculum Vitae (CV)

Publications on PubMed