Staffan Kjelleberg - Selected Publications#


The following list is compiled based on both international recognition of scientific impact as well as number of citations (as of February 2022).

1. Kjelleberg S., Hermansson M., Marden P. and Jones G.W. (1987) The transient phase between growth and nongrowth of heterotrophic bacteria, with emphasis on the marine-environment. Annual Review of Microbiology 41: 25-49. [380 citations]

This review focuses on the physiological and molecular processes of the bacterial downshift from growth to nongrowth induced by substrate limitations. The premise is that non-growing bacteria are active and participate in the carbon flow in the environment, providing evidence of life history mechanisms for survival, competition and proliferation in nutrient discontinuous environments, which are the default state in all ecosystems. This publication marks the beginning of a new paradigm founded on molecular and physiological studies of starved/non-growing bacteria.

2. Hentzer M., Wu H., Andersen J. B., Riedel K., Rasmussen T. B., Bagge N., Kumar N., Schembri M. A., Song Z. J., Kristoffersen P., Manefield M., Costerton J. W., Molin S., Eberl L., Steinberg P., Kjelleberg S., Hoiby N. and Givskov M. (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO Journal 22: 3803-3815. [1588 citations]

On the basis of the discovery that natural marine derived furanone compounds act as bacterial quorum sensing blockers (Manefield M. … Kjelleberg S.A. (1999) Microbiology 145: 283-291), this paper presented the first use of an antimicrobial synthetic furanone-based molecule to interfere in bacterial quorum sensing systems and thereby inhibit virulence expression in bacterial pathogens.

3. Matz, C., McDougald, D., Moreno, A.M., Yung, P.Y., Yildiz, F.H. and Kjelleberg, S., (2005). Biofilm formation and phenotypic variation enhance predation-driven persistence of Vibrio cholerae. Proceedings of the National Academy of Sciences of the United States of America 102: 16819-16824. [223 citations]

This study provides a mechanistic explanation of how opportunistic bacterial pathogens survive and proliferate during stages of the life history outside the host. Vibrio cholerae is an opportunistic biofilm-forming pathogen that spends part if its life history in aquatic habitats and causes seasonal cholera outbreaks and epidemics. The paper reports on the discovery that V. cholerae in the biofilm state in the environment imparts protection from protozoan grazing by secreting anti-protozoan molecules. Conversely, planktonic cells are readily preyed upon by protozoa.

4. Allesen-Holm M., Barken K. B., Yang L., Klausen M., Webb J. S., Kjelleberg S., Molin S., Givskov M. and Tolker-Nielsen T. (2006) A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms. Molecular Microbiology 59: 1114-1128. [1052 citations]

It is now understood that extracellular DNA (eDNA) is a core biofilm matrix component. This paper was among the first studies on eDNA and demonstrates that the export of DNA from microbial cells to the matrix relies on extracellular signalling regulation, and that eDNA locates specifically within key structures of the extracellular domain. Understanding these mechanisms enables development of targeted biofilm control technologies.

5. Barraud N., Hassett D. J., Hwang S.-H., Rice S. A., Kjelleberg S. and Webb J. S. (2006) Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa. Journal of Bacteriology 188: 7344-7353. [838 citations]

This paper documents the discovery of nitric oxide as a biofilm dispersing signal. Combined with antimicrobial agents it effectively controls persistent biofilms by detaching the cells which are susceptible to traditional and novel antimicrobials. This targeted approach provides effective control of persistent biofilm-based infections as well as biofilm control applications in engineered settings, and forms the basis of subsequent double-warhead delivery technologies developed by Kjelleberg et al.

6. Burke C., Steinberg P., Rusch D., Kjelleberg S. and Thomas T. (2011) Bacterial community assembly based on functional genes rather than species. Proceedings of the National Academy of Sciences USA 108: 14288-14293. [701 citations]

This study (and its predecessor: ISME Journal (2011) 5: 590-600) present a novel approach to understanding microbial biofilm community structure and function. Given the highly diverse and stochastic assemblages of micoorganisms in nature, it was found using taxonomic and functional gene assessment that the latter (rather than the taxonomy-based species concept) explains the community structure of surface-associated bacterial consortia.

7. McDougald D., Rice S. A., Barraud N., Steinberg P. D. and Kjelleberg S. (2012) Should we stay or should we go: Mechanisms and ecological consequences for biofilm dispersal. Nature Reviews Microbiology 10: 39-50. [780 citations]

This paper addresses for the first time the last stage of the biofilm lifecycle. i.e., that of dispersal, detailing the evolutionary aspect of biofilm dispersal through the integration of molecular microbiology with eukaryotic ecological and evolutionary theory. The conceptual framework established in this paper now forms the basis of understanding biofilm biology in a multidisciplinary context.

8. Tan C. H., Koh K. S., Xie C., Tay M., Zhou Y., Williams R., Ng W. J., Rice S. A. and Kjelleberg S. (2014) The role of quorum sensing signalling in EPS production and the assembly of a sludge community into aerobic granules. ISME Journal 8: 1186-1197. [275 citations]

This paper establishes the ecological role of quorum sensing (QS) in complex, multi-species communities, in the context of community assembly, incorporating a combined experimental and theoretical approach. The complex community investigated involved using a long-term microbial granulation bioreactor, demonstrating that very low concentrations of bacterial signalling molecules regulate granule formation. This was the first in a series of novel papers by Kjelleberg et al. on the means by which bacterial biofilm communities – from simple to highly species-diverse - are established, with implications for harnessing and controlling biofilms in all natural and engineered systems.

9. Flemming H.-C., Wingender J., Szewzyk U., Steinberg P., Rice S. A. and Kjelleberg S. (2016) Biofilms: An emergent form of bacterial life. Nature Reviews Microbiology 14: 563-575. [2642 citations]

This review establishes the importance of the extracellular polymeric matrix in establishing the emergent properties that are key to the success of microbial biofilms, including social cooperation, resource capture and enhanced resistance to antimicrobials.

10. Seviour, T., Winnerdy, F.R., Wong, L.L., Shi, X., Mugunthan, S., Foo, Y.H., Castaing, R., Adav, S.S., Subramoni, S., Kohli, G.S., Shewan, H.M., Stokes, J.R., Rice, S.A., Phan, A.T. and Kjelleberg, S., (2021). The biofilm matrix scaffold of Pseudomonas aeruginosa contains G-quadruplex extracellular DNA structures. npj Biofilms and Microbiomes 7: 27. [1 citation]

This newly-published research establishes the critical role of extracellular DNA in the biofilm matrix as a foundational biofilm property, revealing the eDNA fibres are in the form of G-quadruplex structures and are hence distinct from chromosomal DNA. This also explains the visco-elastic network properties of the biofilm matrix. Furthermore, this finding challenges the long-held concept that exopolysaccharides are the key components of matrix structure, with implications for biofilm control.

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