Maier, Berenike | Higgins, Paul - B 08
Correlating biofilm structure with antibiotic tolerance

Prof. Dr. Berenike Maier
Institute for Biological Physics | Center for Molecular Biosciences
CMMC - PI - B 08
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Institute for Biological Physics | Center for Molecular Biosciences
Zülpcher Str. 47a
50674 Cologne

Dr. Paul Higgins
Institute for Medical Microbiology, Immunology and Hygiene
CMMC - Co-PI - B 08
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Institute for Medical Microbiology, Immunology and Hygiene
Goldenfelsstraße 19-21
50935 Cologne
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.
- 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. - We will investigate how colony formation affects genome-wide gene expression and correlate differential gene expression to tolerance.
- 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

Lab Website
For more information (research, lab members etc.), please check the research website.
Affiliations - Berenike Maier
Affiliations - Paul Higgins
Publications generated during 1/2023-12/2025 with CMMC affiliation
2025
- Wielert I, Kraus-Römer S, Volkmann TE, Craig L, Higgins PG, Maier B. Pilin antigenic variants impact gonococcal lifestyle and antibiotic tolerance by modulating interbacterial forces. PLoS Biol. 2025 Jan 30;23(1):e3003022. doi: 10.1371/journal.pbio.3003022. Epub ahead of print. PMID: 39883727.
2024
- Sithu Shein AM, Hongsing P, Khatib A, Phattharapornjaroen P, Miyanaga K, Cui L, Shibuya K, Amarasiri M, Monk PN, Kicic A, Chatsuwan T, Higgins PG, Abe S, Wannigama DL. Phage therapy could be key to conquering persistent bacterial lung infections in children. NPJ Antimicrob Resist. 2024 Oct 10;2(1):31. doi: 10.1038/s44259-024-00045-4. PMID: 39843534; PMCID: PMC11721074.
- Shein AMS, Wannigama DL, Hurst C, Monk PN, Amarasiri M, Wongsurawat T, Jenjaroenpun P, Phattharapornjaroen P, Ditcham WGF, Ounjai P, Saethang T, Chantaravisoot N, Badavath VN, Luk-In S, Nilgate S, Rirerm U, Srisakul S, Kueakulpattana N, Laowansiri M, Rad SMAH, Wacharapluesadee S, Rodpan A, Ngamwongsatit N, Thammahong A, Ishikawa H, Storer RJ, Leelahavanichkul A, Ragupathi NKD, Classen AY, Kanjanabuch T, Pletzer D, Miyanaga K, Cui L, Hamamoto H, Higgins PG, Kicic A, Chatsuwan T, Hongsing P, Abe S. Phage cocktail amikacin combination as a potential therapy for bacteremia associated with carbapenemase producing colistin resistant Klebsiella pneumoniae. Sci Rep. 2024 Nov 22;14(1):28992. doi: 10.1038/s41598-024-79924-9. PMID: 39578508; PMCID: PMC11584731.
- Opazo-Capurro A, Xanthopoulou K, Arazo Del Pino R, González-Muñoz P, Matus-Köhler M, Amsteins-Romero L, Jerez-Olate C, Hormazábal JC, Vera R, Aguilera F, Fuller S, Higgins PG, González-Rocha G. Co-Occurrence of Two Plasmids Encoding Transferable blaNDM-1 and tet(Y) Genes in Carbapenem-Resistant Acinetobacter bereziniae. Genes (Basel). 2024 Sep 17;15(9):1213. doi: 10.3390/genes15091213. PMID: 39336804; PMCID: PMC11431271.
- Wannigama DL, Amarasiri M, Phattharapornjaroen P, Hurst C, Modchang C, Besa JJV, Miyanaga K, Cui L, Fernandez S, Huang AT, Ounjai P; Pathogen Hunters Research Team; Singer AC, Ragupathi NKD, Furukawa T, Sei K, Nanbo A, Leelahavanichkul A, Kanjanabuch T, Chatsuwan T, Higgins PG, Sano D, Kicic A, Rockstroh JK, Siow R, Trowsdale S, Hongsing P, Khatib A, Shibuya K, Abe S. Community-based mpox and sexually transmitted disease surveillance using discarded condoms in the global south. Lancet Infect Dis. 2024 Oct;24(10):e610-e613. doi: 10.1016/S1473-3099(24)00514-0. Epub 2024 Aug 21. PMID: 39181146.
- Shein AMS, Hongsing P, Smith OK, Phattharapornjaroen P, Miyanaga K, Cui L, Ishikawa H, Amarasiri M, Monk PN, Kicic A, Chatsuwan T, Pletzer D, Higgins PG, Abe S, Wannigama DL. Current and novel therapies for management of Acinetobacter baumannii-associated pneumonia. Crit Rev Microbiol. 2024 Jul 1:1-22. doi: 10.1080/1040841X.2024.2369948. Epub ahead of print. PMID: 38949254.
- Wannigama DL, Amarasiri M, Phattharapornjaroen P, Hurst C, Modchang C, Chadsuthi S, Anupong S, Miyanaga K, Cui L, Fernandez S, Huang AT, Ounjai P, Singer AC, Ragupathi NKD, Sano D, Furukawa T, Sei K, Leelahavanichkul A, Kanjanabuch T, Chatsuwan T, Higgins PG, Nanbo A, Kicic A, Siow R, Trowsdale S, Hongsing P, Khatib A, Shibuya K, Abe S, Ishikawa H; Pathogen Hunters Research Team. Increased faecal shedding in SARS-CoV-2 variants BA.2.86 and JN.1. Lancet Infect Dis. 2024 Jun;24(6):e348-e350. doi: 10.1016/S1473-3099(24)00155-5. Epub 2024 Mar 21. PMID: 38522445.
- Wannigama DL, Amarasiri M, Phattharapornjaroen P, Hurst C, Modchang C, Chadsuthi S, Anupong S, Miyanaga K, Cui L, Werawatte W, Ali Hosseini Rad SM, Fernandez S, Huang AT, Vatanaprasan P, Saethang T, Luk-In S, Storer RJ, Ounjai P, Tacharoenmuang R, Ragupathi NKD, Kanthawee P, Cynthia B, Besa JJV, Leelahavanichkul A, Kanjanabuch T, Higgins PG, Nanbo A, Kicic A, Singer AC, Chatsuwan T, Trowsdale S, Furukawa T, Sei K, Sano D, Ishikawa H, Shibuya K, Khatib A, Abe S, and Hongsing P (2024). Wastewater-based epidemiological surveillance of SARS-CoV-2 new variants BA.2.86 and offspring JN.1 in south and Southeast Asia. J Travel Med. doi:10.1093/jtm/taae040.
- Wannigama DL, Hurst C, Phattharapornjaroen P, Hongsing P, Sirichumroonwit N, Chanpiwat K, Rad SMA, Storer RJ, Ounjai P, Kanthawee P, Ngamwongsatit N, Kupwiwat R, Kupwiwat C, Brimson JM, Devanga Ragupathi NK, Charuluxananan S, Leelahavanichkul A, Kanjanabuch T, Higgins PG, Badavath VN, Amarasiri M, Verhasselt V, Kicic A, Chatsuwan T, Pirzada K, Jalali F, Reiersen AM, Abe S, Ishikawa H, and Team CO-ET (2024). Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial. EClinicalMedicine70, 102517. doi:10.1016/j.eclinm.2024.102517.
2023
- Shein AMS, Wannigama DL, Hurst C, Monk PN, Amarasiri M, Badavath VN, Phattharapornjaroen P, Ditcham WGF, Ounjai P, Saethang T, Chantaravisoot N, Thuptimdang W, Luk-In S, Nilgate S, Rirerm U, Tanasatitchai C, Kueakulpattana N, Laowansiri M, Liao T, Kupwiwat R, Rojanathanes R, Ngamwongsatit N, Thammahong A, Ishikawa H, Pletzer D, Leelahavanichkul A, Ragupathi NKD, Wapeesittipan P, Ali Hosseini Rad SM, Kanjanabuch T, Storer RJ, Miyanaga K, Cui L, Hamamoto H, Higgins PG, Kicic A, Chatsuwan T, Hongsing P, Abe S. Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection. Biomed Pharmacother. 2023 Oct 28;168:115793. doi: 10.1016/j.biopha.2023.115793. Epub ahead of print. PMID: 39491417.
- 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.