Microbial Dormancy


Dormancy may be defined as a reversible state of low metabolic activity, in which cells can persist for extended periods without division; we shall see that this often corresponds to a state in which cells are not “alive” in the sense of being able to form a colony when plated on a suitable solid medium, but one in which they are not “dead” in that when conditions are more favourable they can revert to a state of “aliveness” as so defined. The study of microbial dormancy forms the subject of a collaborative project with Prof. Mike Young of UW Aberystwyth and Prof. Arseny S. Kaprelyants and his group at the Bakh Institute of Biochemistry, Russian Academy of Sciences, Moscow. In particular by exploiting flow cytometry to analyse the properties of individual cells we have been able to obtain conditions in which the resuscitation of dormant cells (of Micrococcus luteus) definitely occurs, and where an increase in plate count at constant total count due to regrowth of viable cells can be excluded. Viable cells produce a pheromonal factor which is necessary for such resuscitation, and this system represents the first example of an autocrine bacterial growth factor or cytokine. An interview on the subject I did with Richard Longland published online in 2016 is here.

Here is a list of publications on dormancy and resuscitation:

Kell, D.B., Potgieter, M., and Pretorius, E. (2015). Individuality, phenotypic differentiation, dormancy and ‘persistence’ in culturable bacterial systems: commonalities shared by environmental, laboratory, and clinical microbiology. F1000Research 4, 179. doi: DOI:10.12688/f1000research.6709.1.

Kell, D.B., and Pretorius, E. (2015). On the translocation of bacteria and their lipopolysaccharides between blood and peripheral locations in chronic, inflammatory diseases: the central roles of LPS and LPS-induced cell death Integr Biol 7, 1339-1377. doi: DOI: 10.1039/C5IB00158G.

Potgieter, M., Bester, J., Kell, D.B., and Pretorius, E. (2015). The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol Rev 39, 567-591. doi: http://dx.doi.org/10.1093/femsre/fuv013.

Mukamolova, G.V., Murzin, A.G., Salina, E.G., Demina, G.R., Kell, D.B., Kaprelyants, A.S., and Young, M. (2006). Muralytic activity of Micrococcus luteus Rpf and its relationship to physiological activity in promoting bacterial growth and resuscitation. Mol Microbiol 59, 84-98.

Kell DB, Mukamolova GV, Finan CL, Zhao H, Goodacre R, Kaprelyants AS, Young M. 2003. Resuscitation of ‘uncultured’ microorganisms. In: Bull AT, editor. Microbial diversity and bioprospecting. Washington, DC: American Society for Microbiology.

Mukamolova GV, Kaprelyants AS, Kell DB, Young M. 2003. Adoption of the transiently non-culturable state – a bacterial survival strategy? Adv. Micr. Physiol. 47:65-129.

Mukamolova GV, Turapov OA, Kazarian K, Telkov M, Kaprelyants AS, Kell DB, Young M. 2002. The rpf gene of Micrococcus luteus encodes an essential secreted growth factor. Mol Microbiol 46(3):611-21.

Mukamolova GV, Turapov OA, Young DI, Kaprelyants AS, Kell DB, Young M. 2002. A family of autocrine growth factors in Mycobacterium tuberculosis. Mol Microbiol 46(3):623-35.

Shleeva MO, Bagramyan K, Telkov MV, Mukamolova GV, Young M, Kell DB, Kaprelyants AS. 2002. Formation and resuscitation of ‘non-culturable’ cells of Rhodococcus rhodochrous and Mycobacterium tuberculosis in prolonged stationary phase. Microbiology 148(Pt 5):1581-91.

Biketov S, Mukamolova GV, Potapov V, Gilenkov E, Vostroknutova G, Kell DB, Young M, Kaprelyants AS. 2000. Culturability of Mycobacterium tuberculosis cells isolated from murine macrophages: a bacterial growth factor promotes recovery. FEMS Immunol. Med. Microbiol. 29(4):233-240.

Kaprelyants AS, Mukamolova GV, Votyakova TV, Davey HM, Kell DB. 2000. Dormancy in non-sporulating bacteria: its significance for environmental monitoring. In: Stopa PJ, Bartoszcze MA, editors. Rapid Methods for Monitoring the Environment for Biological Hazards. Dordrecht: Kluwer Academic Publishers. p 49-65.

Davey HM, Kaprelyants AS, Weichart DH, Kell DB. 1999. Approaches to the estimation of microbial viability using flow cytometry. In: Robinson JP, editor. Current Protocols in Cytometry: Volume 11 Microbial Cytometry. New York: Wiley. p 11.3.1-11.3.20.

Kaprelyants AS, Mukamolova GV, Kormer SS, Weichart DH, Young M, Kell DB. 1999. Intercellular signalling and the multiplication of prokaryotes: bacterial cytokines. Symp. Soc. Gen. Microbiol. 57:33-69.

Mukamolova GV, Kormer SS, Kell DB, Kaprelyants AS. 1999. Stimulation of the multiplication of Micrococcus luteus by an autocrine growth factor. Arch. Microbiol. 172(1):9-14.

Barer MR, Kaprelyants AS, Weichart DH, Harwood CR, Kell DB. 1998. Microbial stress and culturability: conceptual and operational domains. Microbiology UK 144(Pt8):2009-2010.

Kell DB, Kaprelyants AS, Weichart DH, Harwood CL, Barer MR. 1998. Viability and activity in readily culturable bacteria: a review and discussion of the practical issues. Antonie van Leeuwenhoek 73:169-187.

Mukamolova GV, Kaprelyants AS, Young DI, Young M, Kell DB. 1998. A bacterial cytokine. Proc. Natl. Acad. Sci. 95:8916-8921.

Mukamolova GV, Yanopolskaya ND, Kell DB, Kaprelyants AS. 1998. On resuscitation from the dormant state of Micrococcus luteus. Antonie van Leeuwenhoek 73:237-243.

Votyakova TV, Mukamolova GV, ShteinMargolina VA, Popov VI, Davey HM, Kell DB, Kaprelyants AS. 1998. Research on the heterogeneity of a Micrococcus luteus culture during an extended stationary phase: Subpopulation separation and characterization. Microbiology (Russia) 67(1):71-77.

Kaprelyants, A.S. & Kell, D.B. 1996. Do bacteria need to communicate with each other for growth? Trends Microbiol. 4, 237-242.

Kaprelyants, A.S., Mukamolova, G.V., Davey, H.M. & Kell, D.B. 1996. Quantitative analysis of the physiological heterogeneity within starved cultures of Micrococcus luteus using flow cytometry and cell sorting, Appl. Env. Microbiol. 62, 1311-1316.

Kell, D.B., Davey, H.M., Mukamolova, G.V., Votyakova, T.V. & Kaprelyants, A.S. 1995. A summary of recent work on dormancy in non-sporulating bacteria: significance for marine microbiology and biotechnology. J. Marine Biotechnol. 3, 24-25.

Mukamolova G.V., Yanopolskaya N.D., Votyakova T.V., Popov V.I., Kaprelyants A.S. & Kell D.B. 1995. Biochemical changes accompanying the long-term starvation of Micrococcus luteus cells in spent growth medium. Arch. Microbiol. 163, 373- 379.

Mukamolova, G.V., Kaprelyants, A.S. & Kell, D.B. 1995. Secretion of an antibacterial factor during resuscitation of dormant cells in Micrococcus luteus cultures held in an extended stationary phase. Antonie van Leeuwenhoek, 67, 289-295.

Kell, D.B., Kaprelyants, A.S. & Grafen, A. 1995. On pheromones, social behaviour and the functions of secondary metabolism in bacteria. Trends Ecol. Evolution 10, 126-129.

Kell, D.B., Davey, H.M., Mukamolova, G.V., Votyakova, T.V. & Kaprelyants, A.S. 1994. Life, death, dormancy and social resuscitation in non-sporulating bacteria: relationships with the energetic status of individual cells. What is controlling life? 50 years after Schrödinger’s What is Life? (E. Gnaiger, F.N. Gellerich & M. Wyss, eds) Modern Trends in Biothermokinetics Vol 3, 252-254. Innsbruck University Press, Innsbruck.

Votyakova, T.V., Kaprelyants, A.S. & Kell, D.B. 1994. Influence of viable cells on the resuscitation of dormant cells in Micrococcus luteus cultures held in extended stationary phase. The population effect. Appl. Env. Microbiol. 60, 3284-3291.

Kaprelyants, A.S., Mukamolova, G.V. & Kell, D.B. 1994. Estimation of dormant Micrococcus luteus cells by penicillin lysis and by resuscitation in cell-free spent culture medium at high dilution. FEMS Microbiol. Lett., 115, 347-352.

Kaprelyants, A.S. & Kell, D.B. 1993. Dormancy in stationary-phase cultures of Micrococcus luteus: flow cytometric analysis of starvation and resuscitation. Appl. Env. Microbiol. 59, 3187-3196.

Kaprelyants, A.S., Gottschal, J.C. & Kell, D.B. 1993. Dormancy in nonsporulating bacteria. FEMS Microbiol. Rev. 104, 271-286.

Davey, H.M., Kaprelyants, A.S. & Kell, D.B. 1993. Flow cytometric analysis, using rhodamine 123, of Micrococcus luteus at low growth rate in chemostat culture. In Flow cytometry in microbiology, ed. D. Lloyd, Springer-Verlag, Heidelberg, pp. 83-93.

Davey, H.M., Davey, C.L. & Kell, D.B. 1993. On the determination of the size of microbial cells using flow cytometry. In Flow cytometry in microbiology, ed. D. Lloyd, Springer-Verlag, Heidelberg, pp. 49-65.

Kaprelyants, A.S. & Kell, D.B. 1993. The use of 5-cyano-2,3-ditolyl tetrazolium chloride and flow cytometry for the visualisation of respiratory activity in individual cells of Micrococcus luteus. J. Microbiol. Methods. 17, 115-122.

Kaprelyants, A.S. & Kell, D.B. 1992. Rapid assessment of bacterial viability and vitality using rhodamine 123 and flow cytometry. J. Appl. Bacteriol., 72, 410-422.

Kell, D.B., Ryder, H.M., Kaprelyants, A.S. & Westerhoff, H.V. 1991. Quantifying heterogeneity: flow cytometry of bacterial cultures. Antonie van Leeuwenhoek 60, 145-158.