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Distinct bacterial population dynamics and disease dissemination after biofilm dispersal and disassembly

The ISME Journal volume 17, pages 1290–1302 (2023)Cite this article

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Abstract

Microbial communities that form surface-attached biofilms must release and disperse their constituent cells into the environment to colonize fresh sites for continued survival of their species. For pathogens, biofilm dispersal is crucial for microbial transmission from environmental reservoirs to hosts, cross-host transmission, and dissemination of infections across tissues within the host. However, research on biofilm dispersal and its consequences in colonization of fresh sites remain poorly understood. Bacterial cells can depart from biofilms via stimuli-induced dispersal or disassembly due to direct degradation of the biofilm matrix, but the complex heterogeneity of bacterial populations released from biofilms rendered their study difficult. Using a novel 3D-bacterial “biofilm-dispersal-then-recolonization” (BDR) microfluidic model, we demonstrated that Pseudomonas aeruginosa biofilms undergo distinct spatiotemporal dynamics during chemical-induced dispersal (CID) and enzymatic disassembly (EDA), with contrasting consequences in recolonization and disease dissemination. Active CID required bacteria to employ bdlA dispersal gene and flagella to depart from biofilms as single cells at consistent velocities but could not recolonize fresh surfaces. This prevented the disseminated bacteria cells from infecting lung spheroids and Caenorhabditis elegans in on-chip coculture experiments. In contrast, EDA by degradation of a major biofilm exopolysaccharide (Psl) released immotile aggregates at high initial velocities, enabling the bacteria to recolonize fresh surfaces and cause infections in the hosts efficiently. Hence, biofilm dispersal is more complex than previously thought, where bacterial populations adopting distinct behavior after biofilm departure may be the key to survival of bacterial species and dissemination of diseases.

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Fig. 1: Tracking of physiological biofilm dispersal using a bacterial “biofilm-dispersal-and-recolonization” (BDR) microfluidic chip.
Fig. 2: Dynamics of CID mediated by c-di-GMP signalling reduction.
Fig. 3: Dynamics of biofilm EDA.
Fig. 4: Bacterial cells released by CID and EDA possessed differing physiologies.
Fig. 5: Recolonization dynamics of CID-released bacteria.
Fig. 6: Recolonization dynamics of EDA-released bacteria.
Fig. 7: Virulence of bacterial cells released from biofilm CID and EDA in eukaryotic models.
Fig. 8: Schematic diagram displaying the differences between biofilm chemical-induced dispersal (CID) and biofilm enzymatic disassembly (EDA).

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This research is supported by The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology Startup Grant (BE2B), Departmental General Research Fund (UALB), One-line account (ZVVV), Environmental and Conservation Fund (ECF-48/2019 and ECF-84/2021), Health and Medical Research Fund (HMRF-20190302), and State Key Laboratory of Chemical Biology and Drug Discovery Fund (1-BBX8). This work was also supported by the City University of Hong Kong [7005208,7005464,7020002,9610430,9667220]; Hong Kong Center for Cerebro- Cardiovascular Health Engineering (COCHE); Research Grants Council of the Hong Kong Special Administrative Region [21200921]; Pneumoconiosis Compensation Fund Board [9211276]; and the Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Shenzhen Park Project (HZQB-KCZYZ-2021017).

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Author notes

  1. These authors contributed equally: Yanlin Deng, Haojun Hua.

Authors and Affiliations

  1. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China

    Yeping Ma & Song Lin Chua

  2. Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR, 999077, China

    Yanlin Deng, Haojun Hua & Bee Luan Khoo

  3. Hong Kong Center for Cerebro-Cardiovascular Health Engineering (COCHE), Kowloon, Hong Kong SAR, 999077, China

    Bee Luan Khoo

  4. Department of Precision Diagnostic and Therapeutic Technology, City University of Hong Kong Shenzhen-Futian Research Institute, Shenzhen, 518057, China

    Bee Luan Khoo

  5. State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China

    Song Lin Chua

  6. Shenzhen Key Laboratory of Food Biological Safety Control, Shenzhen, China

    Song Lin Chua

  7. Research Centre for Deep Space Explorations (RCDSE), The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China

    Song Lin Chua

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Contributions

SLC and BLK designed methods and experiments. YM and YD performed laboratory experiments and analyzed the data. YM, YD, BLK and SLC interpreted the results and wrote the paper. All authors have contributed to, seen, and approved the manuscript.

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Correspondence to Bee Luan Khoo or Song Lin Chua.

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Ma, Y., Deng, Y., Hua, H. et al. Distinct bacterial population dynamics and disease dissemination after biofilm dispersal and disassembly. ISME J 17, 1290–1302 (2023). https://doi.org/10.1038/s41396-023-01446-5

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