Universität zu Köln

Cronenberg, Tom, Hennes, Marc ORCID: 0000-0002-6592-9297, Wielert, Isabelle and Maier, Berenike ORCID: 0000-0001-6971-9927 (2021). Antibiotics modulate attractive interactions in bacterial colonies affecting survivability under combined treatment. PLoS Pathog., 17 (2). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7374

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Abstract

Biofilm formation protects bacteria from antibiotics. Very little is known about the response of biofilm-dwelling bacteria to antibiotics at the single cell level. Here, we developed a cell-tracking approach to investigate how antibiotics affect structure and dynamics of colonies formed by the human pathogen Neisseria gonorrhoeae. Antibiotics targeting different cellular functions enlarge the cell volumes and modulate within-colony motility. Focusing on azithromycin and ceftriaxone, we identify changes in type 4 pilus (T4P) mediated cell-to-cell attraction as the molecular mechanism for different effects on motility. By using strongly attractive mutant strains, we reveal that the survivability under ceftriaxone treatment depends on motility. Combining our results, we find that sequential treatment with azithromycin and ceftriaxone is synergistic. Taken together, we demonstrate that antibiotics modulate T4P-mediated attractions and hence cell motility and colony fluidity. Author summary Aggregation into colonies and biofilms can enhance bacterial survivability under antibiotic treatment. Aggregation requires modulation of attractive forces between neighboring bacteria, yet the link between attraction and survivability is poorly characterized. Here, we quantify these attractive interactions and show that different antibiotics enhance or inhibit them. Live-cell tracking of single cells in spherical colonies enables us to correlate attractive interactions with single cell motility and colony fluidity. Even moderate changes in cell-to-cell attraction caused by antibiotics strongly impact on within-colony motility. Vice versa, we reveal that motility correlates with survivability under antibiotic treatment. In summary, we demonstrate a link between cellular attraction, colony fluidity, and survivability with the potential to optimize the treatment strategy of commonly used drug combinations.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cronenberg, Tom UNSPECIFIED UNSPECIFIED UNSPECIFIED Hennes, Marc UNSPECIFIED orcid.org/0000-0002-6592-9297 UNSPECIFIED Wielert, Isabelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Maier, Berenike UNSPECIFIED orcid.org/0000-0001-6971-9927 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-563684
DOI:	10.1371/journal.ppat.1009251
Journal or Publication Title:	PLoS Pathog.
Volume:	17
Number:	2
Date:	2021
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7374
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language UNITED-STATES; TOLERANCE; RETRACTION; RESISTANCE Multiple languages Microbiology; Parasitology; Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56368