Newcastle University

Introduction

The Gerdes group at Newcastle University uses Escherichia coli as a model organism to study basic problems of how bacteria grow and divide. Using the vast information available in the DNA databases (>1,000 prokaryotic genomes), we can identify genes of general biological importance and rapidly obtain new insights of the genetics, cytology and molecular biology of the gene products and hence infer gene functions in other organisms. We have recently identified a novel cell division factor and noumerous messenger RNA cleaving enzymes that are activated by nutritional stress - these latter enzymes are functionally related to RNAi in eukaryotes.

Roles and Responsibilities

Editor of Molecular Microbiology

Qualifications

1983 Masters Degree in Molecular Genetics at SDU, Odense, Denmark
1986 Ph. D. Degree in Molecular Genetics, Technical University, Copenhagen

Previous Positions

1986 -1987 Assistant Professor, Department of Microbiology, Technical
University of Denmark, Copenhagen
1987 - 1988 Research Chemist at Novo Nordisk Inc., Bagsværd, Denmark
1988 - 1992 Assistant Professor, Department of Molecular Biology, University of Southern Denmark (SDU)
1990 Short term Research Fellow, Department of Microbiology, BMC, Uppsala University, Sweden
1992 - 2002 Associate Professor, Department of Molecular Biology, SDU
2002 - 2006 Full Professor in Molecular Microbiology, Department of Biochemistry & Molecular Biology (SDU)

Memberships

American Society for Microbiology (since 1981)
European Molecular Biology Organization (since 2005) (EMBO)
Society for General Microbiology, UK (since 2006)
American Academy of Microbiology (since 2008)
American Society for Biochemistry and Molecular Biology (since 2008)

Research Interests

The main present research areas are

1. Mechanisms of translational quality control

a. Trans-translation performed by the unusual tmRNA, a small bifunctional RNA molecule

b. Messenger RNA interferases encoded by toxin – antitoxin genes

2. Bacterial cell division and cell wall

a. FtsZ ring dynamics

b. Plasmid segregation mechanisms

c. Bacterial dynamin like proteins

d. Regulators of autolysins

1a Translational quality control by tmRNA-mediated trans-translation

The bacterial tmRNA is so-named for its dual tRNA-like and mRNA-like nature. tmRNA, also known as 10Sa RNA, performs the remarkable trans-translation process, adding a C-terminal peptide tag to the unfinished protein emerging from a stalled ribosome.

Fig.1: The ends of tmRNA fold together to form a tRNA-like structure charged with alanine.

1b Messenger RNA interferases encoded by toxin – antitoxin genes

Toxin – antitoxin (TA) genes were discovered on plasmids because they confer plasmid stabilization by killing or inhibiting the growth of plasmid-free cells (Gerdes et al., 1986b). Later analyses showed that TA loci are abundant on bacterial and archaeal chromosomes (Gerdes et al., 1986a; Gotfredsen and Gerdes, 1998; Gerdes, 2000). Two types of TA gene loci are known: Type I loci encode metabolically unstable antisense RNAs that inhibit the translation of a stable mRNA that codes for a toxin. The paradigm Type I TA system is the hok/sok locus of plasmid R1, which is understood at a profound level (Gerdes et al., 1997). Type II TA loci encode a protein antitoxin that combines with and neutralizes a toxin by direct protein-protein contact.

Fig.2 shows the components and interactions of the best-studied TA locus, relBE of E. coli that encodes RelE toxin and RelB antitoxin.

RelB and RelE combine very efficiently and form a non-toxic RelB2E complex. Thus, the cells can grow rapidly even though they contain the RelB2E complex. Two RelB dimers bind non-cooperatively to DNA in the relBE promoter region and represses transcription (Overgaard et al., 2008). However, the RelB2E complex binds cooperatively and stronger to the promoter region and represses transcription more efficiently than RelB2. Thus, during rapid growth (when [RelE] [RelB2] (such as e.g. during amino starvation), an extra RelE molecule enters the RelB2E complex to form a RelB2E2 complex that does not bind to the promoter region (Overgaard et al., 2008). In this way, excess RelE greatly increases the transcription-rate of the strong relBE promoter.

RelE is a messenger RNA interferase that cleaves mRNA positioned at the ribosomal A-site (Christensen and Gerdes, 2003; Pedersen et al., 2003). This observation explains why ectopic overproduction of RelE leads to rapid and efficient inhibition of translation (Gotfredsen and Gerdes, 1998; Pedersen et al., 2002). RelE cleaves enzymatically between the 2nd and 3rd nucleotide of the A-site codon and thereby block further translation by the ribosomes that becomes stalled at the damaged, non-stop mRNA. Consistently, tmRNA mitigates the toxic effect of RelE overproduction by rescuing such stalled ribosomes (Christensen and Gerdes, 2003). Recently, the structure of the Ribosome – RelE complex was solved in a colla-borative effort between the labs of Ditlev Brodersen (Aarhus Univer-sity, DK), Venki Ramakrishnan (LMB-MRC, Cambridge, UK) and ourselves, see Fig.3 (Neubauer et al., 2009).

Fig.3 Structure of the ribosome in complex with RelE, mRNA P-site and E-site tRNA

The pre- and post-cleavage structures obtained confirm that RelE cleaves between the 2nd and 3rd nucleotide of the A-site codon and also explain why RelE needs the ribosome to become active. RelE has an incomplete RNase fold that lacks canonical amino acid residues important for catalysis. Interactions between RelE and the ribosomal A-site compensate for the missing catalytic residues in RelE. Interestingly, RelE homologs that have these residues are catalytically active in vitro without the presence of ribosomes but still cleave mRNA at the ribosomal A-site in vivo.
Before we can understand the biological function of TAs, it is crucial to understand how the systems are activated. RelB is degraded constitutively by Lon protease. Amino acid starvation reduces the synthesis-rates of RelB and RelE and thereby confers an increase in the RelE/RelB ratio. Therefore, degradation of RelB leads to activation of RelE and to a strongly increased transcription-rate of the relBE operon (Christensen et al., 2001; Christensen and Gerdes, 2004; Overgaard et al., 2008). In turn, activation of RelE leads to a reduced level of global cellular translation. Thus, during nutrient limitations, RelE reduces translation. It has many times been stated in the literature by other scientists that RelE blocks translation and thereby induces cell stasis. Indeed, ectopic production of RelE blocks translation and induces cell stasis. However this is a highly artificial condition and in wild type cells, in which RelE is expressed simultaneously with RelB, RelE does not halt translation but rather, reduces it. Thus, at the level of the cell population, RelE activation appears to reduce translation rather than halting it. This is an important distinction. We do not exclude that RelE in some cells leads to a complete shut down of translation and dormancy. However this has still to be shown. What might be the function of reduced translation during starvation? One plausible (and testable) possibility is that the reduction of translation leads to a reduced level of translational errors and therefore to a more efficient utilization of the resources available. We are now obtaining more and more evidence for this hypothesis.

In a tenacious analysis of the completed genomes of 196 bacteria and 22 archaea, we identified and annotated 1240 toxin - antitoxin loci (Pandey and Gerdes, 2005; Jorgensen et al., 2009). The genomic patterns revealed that almost all free-living bacteria and all archaea have many toxin–antitoxin genes. The organisms investigated include major pathogens such as Mycobacterium tuberculosis, Staphylococcus aureus and Pseudomonas aeruginosa. The genome of M. tuberculosis encodes 90 different TA loci some of which are annotated in the Fig4.

Fig.4: Distribution of 60 toxin-antitoxin loci in the M.tuberculosis H37Rv chromosome.

The majority of TA loci encode translational inhibitors, such as RelE described above. Thus, activation of a toxin in a TA complex may lead to reduced cell growth and eventually dormancy (persistence) of the bacterium. It is thus possible that TA loci contribute to the persistence state of pathogenic bacteria such as M. tuberculosis, an interesting aspect that may have practical impact for the understanding of mechanisms of long-term and/or recurrent infections (Ramage et al., 2009).

2 Cell division

Bacterial cells have traditionally been viewed upon as lacking conspicuous intracellular structures. However, employment of new microscopic and protein labeling techniques have uncovered that bacteria are highly organized with multiple intracellular systems that generate localized structures at the sub-cellular level.

2a FtsZ ring dynamics

FtsZ, the essential regulator of bacterial cell division, is a dynamic cytoskeletal protein that forms helices that condense into the Z ring prior to division. The mechanisms that regulate FtsZ helix condensation and Z ring contraction are not yet understood.

We study two coiled-coil proteins of E. coli, ZapA and ZapB that are both recruited early to the Z ring (Goehring et al., 2005; Ebersbach et al., 2008). ZapA interacts directly with FtsZ whereas ZapB is recruited to the Z ring via ZapA (Galli and Gerdes, in press).

Fig.5: ZapA co-localizes with FtsZ, but ZapB does not co-localize with FtsZ/ZapA.

Using high-resolution 3D reconstruction microscopy, we find that ZapA co-localizes with FtsZ, as expected. However, as seen in the Fig.5, surprisingly, ZapB does not co-localize with FtsZ/ZapA. Rather, ZapB seems to form a ring inside the Z ring. We are now trying to understand the molecular basis of this apparent physical separation of FtsZ/ZapA on the one side and ZapB on the other. Importantly, these observations show that Z ring formation and contraction are complicated processes that are regulated by factors external to the ring itself.

2b Plasmid segregation mechanisms

Chromosome segregation in eukaryotic cells is a well understood process. However it has been more difficult to understand how prokaryotic cells segregate their chromosomes, mainly due to a considerably smaller cell size. To study DNA segregation, we use bacterial plasmids as model systems (Gerdes et al., 2004). Three different types of segregation systems, also called partitioning (par) loci, have been identified in prokaryotes. Thus, the common Type I par loci that encode ATPases related to the oscillating MinD protein of E. coli, are found on many plasmids and most chromosomes (Gerdes et al., 2000). Besides ParA, par loci encode a DNA binding protein (ParB) and a DNA centromere site (parC). ParA interacts with ParB bound to parC. Remarkably, plasmid-encoded ParAs form oscillating, spiral-shaped structures that move and position plasmids within the bacterial cell while simultaneously tethering the plasmids to the nucleoid (bacterial chromosome) (Ebersbach and Gerdes, 2001; Ebersbach et al., 2006).

Fig.6: Plasmid-encoded ParAs form oscillating, spiral-shaped structures that move and position plasmids within the bacterial cell, while simultaneously tethering the plasmids to the nucleoid (bacterial chromosome); 1 minute time-frames.

We are currently trying to understand how ParA does this, using both cytology of living cells and in vitro approaches. In living cells, we simultaneously labeled ParA and plasmid with fluorescent proteins, as shown in the left panel of Fig.6 (1 minute between each time-frame) (Ringgaard et al., 2009). ParA-GFP is seen as green spiral-like structures that we assume are cytoskeletal filaments that move the plasmid (red focus) by a pulling mechanism. The cell shown in the left panel contains one plasmid focus that moves back and forth, apparently due to the pulling force generated by disassembling ParA filaments. On time-average this movement leads to positioning of the plasmid focus at mid-cell.

Our results suggest that ParA filament assembly is regulated by ParB bound to parC encoded by the plasmid. This is because ParB/parC stimulates the ATPase activity of ParA. Since ParA-ATP but not ParA-ADP binds to nucleoid DNA, ParB stimulated ATPase activity of ParA is predicted to release ParA from the nucleoid (Ringgaard et al., 2009).

In cases where a cell contains two or more plasmids, ParA mediates regular distribution of the plasmids over the nucleoid (see the right panel of the Figure). The molecular basis behind this regular distribution is not yet understood. However, mathematical modeling of the process showed that the three components ParA, ParB and parC encoded by the plasmid may be sufficient to generate regular plasmid distribution within the cell (Ringgaard et al., 2009). The regular distribution of the plasmids and their stable association with the nucleoid in a simple way explains how Type I par loci mediate efficient plasmid segregation before cell division.

2c Regulators of autolysins

Bacteria are surrounded by a strong external shield, the cell wall that consists of layers of peptidoglycan that is chemically and functionally related to the exoskeletons of some animals. Peptidoglycan is a giant molecule that consists of parallel strands of sugar residues cross-linked by short peptides. This giant, elastic and strong molecule is continuously remodeled (synthesized and degraded) during cell growth and division. Bacterial autolysins are enzymes that can break the covalent bonds in peptidoglycan. E. coli has seven known autolysins that are located outside the cell membrane. Uncontrolled activity of any such autolysin leads to cell lysis and death. Therefore, the activity of these enzymes must be tightly regulated. We are presently attempting to identifying activators and inhibitors of autolysins.

2d Bacterial dynamin like proteins (BDLPs)

BLDPs are large multi-domain proteins that exhibit sequence similarity with eukaryotic dynamins. Dynamins function in fission of cellular membranes. Almost all known bacterial genomes encode at least one BDLP. The biological function of BDLPs is not yet known. We are presently trying to identify the biological function of this large prokaryotic gene family using E. coli as the model organism.

References

Gerdes K, Howard M and Szardenings. Pushing and Pulling in Prokaryotic DNA Segregation, Cell, 2010, in press.

Galli E and Gerdes K. Spatial resolution of two bacterial cell division proteins: ZapA recruits ZapB to the inner face of the Z-ring. Mol Microbiol. 2010 May 11. [Epub ahead of print]

Neubauer C, Gao YG, Andersen KR, Dunham CM, Kelley AC, Hentschel J, Gerdes K, Ramakrishnan V, Brodersen DE. The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE. Cell. 2009 Dec 11;139(6):1084-95. PubMed PMID: 20005802; PubMed Central PMCID: PMC2807027.

Christensen-Dalsgaard M, Jørgensen MG, Gerdes K. Three new RelE-homologous mRNA interferases of Escherichia coli differentially induced by environmental stresses. Mol Microbiol. 2010 Jan;75(2):333-48. Epub 2009 Nov 25. PubMed PMID:
19943910; PubMed Central PMCID: PMC2814082.

Ringgaard S, van Zon J, Howard M, Gerdes K. Movement and equipositioning of plasmids by ParA filament disassembly. Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19369-74. Epub 2009 Nov 11. PubMed PMID: 19906997; PubMed Central
PMCID: PMC2775997.

Christensen,S.K. and Gerdes,K. (2003). RelE toxins from bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA. Mol Microbiol. 48, 1389-1400.

Christensen,S.K. and Gerdes,K. (2004). Delayed-relaxed response explained by hyperactivation of RelE. Mol. Microbiol. 53, 587-597.

Christensen,S.K., Mikkelsen,M., Pedersen,K., and Gerdes,K. (2001). RelE, a global inhibitor of translation, is activated during nutritional stress. Proc. Natl. Acad. Sci. U. S. A 98, 14328-14333.

Ebersbach,G., Galli,E., Moller-Jensen,J., Lowe,J., and Gerdes,K. (2008). Novel coiled-coil cell division factor ZapB stimulates Z ring assembly and cell division. Mol. Microbiol. 68, 720-735.

Ebersbach,G. and Gerdes,K. (2001). The double par locus of virulence factor pB171: DNA segregation is correlated with oscillation of ParA. Proc. Natl. Acad. Sci. U. S. A 98, 15078-15083.

Ebersbach,G., Ringgaard,S., Moller-Jensen,J., Wang,Q., Sherratt,D.J., and Gerdes,K. (2006). Regular cellular distribution of plasmids by oscillating and filament-forming ParA ATPase of plasmid pB171. Mol. Microbiol. 61, 1428-1442.

Gerdes,K. (2000). Toxin-antitoxin modules may regulate synthesis of macromolecules during nutritional stress. Journal of Bacteriology 182, 561-572.

Gerdes,K., Bech,F.W., Jorgensen,S.T., Lobnerolesen,A., Rasmussen,P.B., Atlung,T., Boe,L., Karlstrom,O., Molin,S., and Vonmeyenburg,K. (1986a). Mechanism of Postsegregational Killing by the Hok Gene-Product of the Parb System of Plasmid R1 and Its Homology with the Relf Gene-Product of the Escherichia-Coli Relb Operon. Embo Journal 5, 2023-2029.

Gerdes,K., Gultyaev,A.P., Franch,T., Pedersen,K., and Mikkelsen,N.D. (1997). Antisense RNA-regulated programmed cell death. Annu. Rev. Genet. 31, 1-31.

Gerdes,K., Moller-Jensen,J., and Bugge,J.R. (2000). Plasmid and chromosome partitioning: surprises from phylogeny. Mol. Microbiol. 37, 455-466.

Gerdes,K., Moller-Jensen,J., Ebersbach,G., Kruse,T., and Nordstrom,K. (2004). Bacterial mitotic machineries. Cell 116, 359-366.

Gerdes,K., Rasmussen,P.B., and Molin,S. (1986b). Unique Type of Plasmid Maintenance Function - Postsegregational Killing of Plasmid-Free Cells. Proceedings of the National Academy of Sciences of the United States of America 83, 3116-3120.

Goehring,N.W., Gueiros-Filho,F., and Beckwith,J. (2005). Premature targeting of a cell division protein to midcell allows dissection of divisome assembly in Escherichia coli. Genes Dev. 19, 127-137.

Gotfredsen,M. and Gerdes,K. (1998). The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family. Mol. Microbiol. 29, 1065-1076.

Jorgensen,M.G., Pandey,D.P., Jaskolska,M., and Gerdes,K. (2009). HicA of Escherichia coli defines a novel family of translation-independent mRNA interferases in bacteria and archaea. J. Bacteriol. 191, 1191-1199.

Neubauer,C., Gao,Y.G., Andersen,K.R., Dunham,C.M., Kelley,A.C., Hentschel,J., Gerdes,K., Ramakrishnan,V., and Brodersen,D.E. (2009). The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE. Cell 139, 1084-1095.

Overgaard,M., Borch,J., Jorgensen,M.G., and Gerdes,K. (2008). Messenger RNA interferase RelE controls relBE transcription by conditional cooperativity. Mol. Microbiol. 69, 841-857.

Pandey,D.P. and Gerdes,K. (2005). Toxin - antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes . Nucleic Acids Res. 33, 966-976.

Pedersen,K., Christensen,S.K., and Gerdes,K. (2002). Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol. Microbiol. 45, 501-510.

Pedersen,K., Zavialov,A.V., Pavlov,M.Y., Elf,J., Gerdes,K., and Ehrenberg,M. (2003). The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site. Cell 112, 131-140.

Ramage,H.R., Connolly,L.E., and Cox,J.S. (2009). Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS. Genet. 5, e1000767.

Ringgaard,S., van,Z.J., Howard,M., and Gerdes,K. (2009). Movement and equipositioning of plasmids by ParA filament disassembly. Proc. Natl. Acad. Sci. U. S. A 106, 19369-19374.

PRESENT CO-WORKERS

David Guymer, PhD 

Etienne Maissoneuve, PhD

Andrew Fenton, PhD

Patrick Scheu, PhD

Elisa Galli, M. Sc. 

Kristoffer S. Winther, M. Sc.

Mikkel Christensen-Dalsgaard, M. Sc.

Florian Zardenings, Bach. Sc.

Milena Jaskolska, Bach. Sc.

Lana Shakespeare, Bach. Sc.

Research Roles

At the moment, the Gerdes group consists of 4 post docs and 6 graduate students

Postgraduate Supervision

• Bacterial persistence, Toxin - antitoxins and translation
• Bacterial Cell Division, DNA segregation and related topics

Funding

Current
2010-2013: Wellcome Trust funded project on DNA Segregation Mechanisms in Prokaryotes. £198,000

2009-2013: EC funded grant, partner in the Consortium DIVINOCELL:
Exploiting Gram-negative cell division targets in the test tube to
obtain anti-microbial compounds; €351,000

2008-2011: BBSRC funded grant on the project Bacterial actin MreB in cell morphogenesis £432,556

2008-2011: Wellcome Trust funded grant on the project Nonsense-mediated mRNA decay in prokaryotes - £228,743.

Completed
2005 - 2010: a grant from the The Danish Basic Research Foundation of Dkr 2,400,000,- (ca. £220,000).

2005 - 2007: a grant from the Danish Natural Research Council has established The Centre for Bacterial Genetics. The grant was Dkr 6,800,000,- (ca. £620,000) divided equally on three research groups over three years.

From 1990 to 2000, the group received solid financial support from the Danish Governmental Biotechnology Programmes I,II and III.

From 2000 - 2003, grant from the Danish Biotechnology Instrument Center (DABIC) (Dkr 1,500,000,- ≈ £136,000)

From 1998 to 2001 and from 2002 to 2005, grants from the EC Framework Programmes 4 and 5 (ca. £120,000 and £160,000).

Patents

Gerdes, K. and Molin, S. Stabilized Plasmids.
PCT application no: WO84/01172, Issued 1988. Number in US Patent database: 4760022

Gerdes, K., Molin, S., Rasmussen, PB., and Andersson, P. Stabilization of unstably inherited replicons. Issued 1996. Number in US Patent database: 5545541.

Molin, S., Andersson, P., Gerdes, K., and Klemm, P. Biological Containment. Issued 1997. Number in US Patent database: 5702916 and 5670370

Gerdes, K., Gotfredsen, M., and Grønlund. 1998. Cytotoxin based biological containment. Patent application DK0627/98.

Undergraduate Teaching

Leader of MRes module Molecular Microbiology (MMB8016)

• Winther KS, Gerdes K. Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA. Proceedings of the National Academy of Sciences 2011, 108(8), 7403-7407.
• Howard M, Gerdes K. What is the mechanism of ParA-mediated DNA movement?. Molecular Microbiology 2010, 78(1), 9-12.
• Christensen-Dalsgaard M, Jorgensen MG, Gerdes K. Three new RelE-homologous mRNA interferases of Escherichia coli differentially induced by environmental stresses. Molecular Microbiology 2010, 75(2), 333-348.
• Winther KS, Gerdes K. Ectopic Production of VapCs from Enterobacteria inhibits translation and trans-activates YoeB mRNA Interferase.. Molecular Microbiology 2009, 72(4), 918-930.
• Jørgensen MG, Pandey DP, Jaskolska M, Gerdes K. HicA of Escherichia coli defines a novel family of translation-independent mRNA interferases in bacteria and archaea. Journal of Bacteriology 2009,191 4 1191-1199.
• Ringgaard S, van Zon J, Howard M, Gerdes K. Movement and equipositioning of plasmids by ParA filament disassembly. Proceedings of the National Academy of Sciences of the United States of America 2009, 106(46), 19369-19374.
• Overgaard M, Borch J, Gerdes K. ReIB and ReIE of Escherichia coli form a tight complex that represses transcription via the Ribbon-Helix-Helix Motif in ReIB. Journal of Molecular Biology 2009, 394(2), 1883-196.
• Gerdes K. RodZ, a new player in bacterial cell morphogenesis. EMBO Journal 2009, 28(3), 171-172.
• Neubauer C, Gao YG, Andersen KR, Dunham CM, Kelley AC, Hentschel J, Gerdes K, Ramakrishnan V, Brodersen DE. The Structural Basis for mRNA Recognition and Cleavage by the Ribosome-Dependent Endonuclease RelE. Cell 2009, 139(6), 1084-1095.
• Garcia-Pino A, Christensen-Dalsgaard M, Wyns L, Yarmolinsky M, Magnuson RD, Gerdes K, Loris R. Doc of prophage P1 is inhibited by its antitoxin partner Phd through fold complementation. Journal of Biological Chemistry 2008, 283(45), 30821-30827.
• Overgaard M, Borch J, Jorgensen MG, Gerdes K. Messenger RNA interferase RelE controls relBE transcription by conditional cooperativity. Molecular Microbiology 2008, 69(4), 841-857.
• Ebersbach G, Galli E, Moller-Jensen J, Lowe J, Gerdes K. Novel coiled-coil cell division factor ZapB stimulates Z ring assembly and cell division. Molecular Microbiology 2008, 68(3), 720-735.
• Christensen-Dalsgaard M, Overgaard M, Winther KS, Gerdes K. RNA decay by messenger RNA interferases. Methods in Enzymology 2008,447 521-35.
• Christensen-Dalsgaard M, Gerdes K. Translation affects YoeB and MazF messenger RNA interferase activities by different mechanisms. Nucleic Acids Research 2008, 36(20), 6472-6481.
• Ringgaard S, Lowe J, Gerdes K. Centromere pairing by a plasmid-encoded type I ParB protein. Journal of Biological Chemistry 2007, 282(38), 28216-28225.
• Moller-Jensen J, Gerdes K. Plasmid segregation: Spatial awareness at the molecular level. Journal of Cell Biology 2007. , 179(5), 813-815.
• Gerdes K, Wagner EG. RNA Antitoxins. Current Opinion in Microbiology 2007, 10(2), 117-124.
• Gerdes K, Wagner EGH. RNA antitoxins. Current Opinion in Microbiology 2007, 10(2), 117-124.
• Moller-Jensen J, Ringgaard S, Mercogliano CP, Gerdes K, Lowe J. Structural analysis of the ParR/parC plasmid partition complex. EMBO Journal 2007, 26(20), 4413-4422.
• Cherny I, Overgaard M, Borch J, Bram Y, Gerdes K, Gazit E. Structural and thermodynamic characterization of the Escherichia coli RelBE toxin-antitoxin system: indication for a functional role of differential stability. Biochemistry 2007, 46(43), 12152-12163.
• Kruse T, Blagoev B, Løbner-Olesen A, Wachi M, Sasaki K, Iwai N, Mann M, Gerdes K. Actin homolog MreB and RNA holymerase interact and are both required for chromosome segregation in Escherichia coli. Genes & Development 2006, 20(1), 113-124.
• Faridani OR, Nikravesh A, Pandey DP, Gerdes K, Good L. Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli. Nucleic Acids Research 2006, 34(20), 5915-5922.
• Ebersbach G, Ringgaard S, Møller-Jensen J, Wang Q, Sherratt DJ, Gerdes K. Regular Cellular Distribution of Plasmids by Oscillating and Filament-forming ParA ATPase of Plasmid pB171. Molecular Microbiology 2006,61 6 1428-1442.
• Nieto C, Pellicer T, Balsa D, Christensen SK, Gerdes K, Espinosa M. The chromosomal relBE2 toxin-antitoxin locus of Streptococcus pneumoniae: characterization and use of a bioluminescence resonance energy transfer assay to detect toxin-antitoxin interaction. Molecular Microbiology 2006,59 4 1280-1296.
• Christensen-Dalsgaard M, Gerdes K. Two higBA loci in the Vibrio cholerae super-integron encode mRNA cleaving enzymes and are transcriptionally activated by amino acid starvation. Molecular Microbiology 2006, 62(2), 397-411.
• Kruse T, Gerdes K. Bacterial DNA segregation by the actin-like MreB protein. Trends in Cell Biology 2005,15 7 343-345.
• Ebersbach G, Sherratt DJ, Gerdes K. Partition-associated incompatibility caused by random assortment of pure plasmid clusters. Molecular Microbiology 2005,56 6 1430-1440.
• Ebersbach G, Gerdes K. Plasmid Segregation Mechanisms. Annual Review of Genetics 2005,39 1 453-480.
• Kruse T, Bork-Jensen J, Gerdes K. The morphogenetic MreBCD proteins of Escherichia coli form an essential membrane-bound complex. Molecular Microbiology 2005,55 1 78-89.
• Pandey DP, Gerdes K. Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Research 2005,33 3 966-976.
• Ebersbach G, Gerdes K. Bacterial mitosis: partitioning protein ParA oscillates in spiral-shaped structures and positions plasmids at mid-cell. Molecular Microbiology 2004,52 2 385-398.
• Gerdes K, Møller-Jensen J, Ebersbach G, Kruse T, Nordström K. Bacterial Mitotic Machineries. Cell 2004,116 3 359-366.
• Hoischen C, Bolshoy A, Gerdes K, Diekmann S. Centromere parC of plasmid R1 is curved. Nucleic Acids Research 2004,32 19 5907-5915.
• Christensen S, Gerdes K. Delayed-relaxed-response explained by hyperactivation of RelE. Molecular Microbiology 2004, 53(2), 587-597.
• Moller-Jensen J, Gerdes K. Dynamic instability of a bacterial engine. Science 2004, 306(5698), 987-989.
• Christensen SK, Maenhaut-Michel G, Mine N, Gottesman S, Gerdes K, Van Melderen L. Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: involvement of the yefM-yoeB toxin-antitoxin system. Molecular Microbiology 2004, 51(6), 1705-1717.
• Hunding A, Ebersbach G, Gerdes K. A mechanism for ParB-dependent waves of ParA, a protein related to DNA segregation in prokaryotes. Journal of Molecular Biology 2003, 329(1), 35-43.
• Møller-Jensen J, Borch J, Dam M, Jensen RB, Roepstorff P, Gerdes K. Bacterial Mitosis: ParM of Plasmid R1 Moves Plasmid DNA by an Actin-like Insertional Polymerization Mechanism. Molecular Cell 2003, 12(6), 1477–1487.
• Nordström K, Gerdes K. Clustering versus random segregation of plasmids lacking a partitioning function: a plasmid paradox. Plasmid 2003, 50(2), 95-101.
• Kruse T, Møller-Jensen J, Løbner-Olesen A, Gerdes K. Dysfunctional MreB inhibits chromosome segregation in Escherichia coli. EMBO Journal 2003, 22(19), 5283-5292.
• Christensen S, Gerdes K. RelE proteins from Bacteria and Archaea inhibit protein synthesis by cleavage of translating mRNAs and is counteracted by tmRNA. Molecular Microbiology 2003, 48(5), 1389-1400.
• Pedersen K, Zavialov AV, Pavlov MY, Elf J, Gerdes K, Ehrenberg M. The Bacterial Toxin RelE Displays Codon-Specific Cleavage of mRNAs in the Ribosomal A Site. Cell 2003, 112(1), 131-140.
• Christensen S, Pedersen K, Hansen FG, Gerdes K. Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK toxins cleave translated RNAs and are counteracted by tmRNA. Journal of Molecular Biology 2003, 332(4), 809-819.
• Nagel JH, Gultyaev AP, Oistamo KJ, Gerdes K, Pleij CW. A pH-jump approach for investigating secondary structure refolding kinetics in RNA. Nucleic Acids Research 2002, 30(13), e63.
• Gerdes K, Møller-Jensen J. Antisense RNAs in bacterial programmed cell death. In: Hodgson, D.A., Thomas, C.M, ed. Signals, Switches, Regulons, and Cascades: Control of Bacterial Gene Expression. Cambridge: Cambridge University Press, 2002, pp.183-198.
• Yamamoto T-AM, Gerdes K, Tunnacliffe A. Bacterial Toxin RelE Induces Apoptosis in Human Cells. FEBS Letters 2002, 519(1-3), 191-194.
• van den Ent F, Møller-Jensen J, Amos L, Gerdes K, Löwe J. F-actin-like filaments formed by plasmid segregation protein ParM. EMBO Journal 2002, 21(24), 6935-6943.
• Møller-Jensen J, Jensen RB, Gerdes K. Prokaryotic DNA segregation by an actin-like filament. The EMBO Journal 2002, 21(12), 3119-3127.
• Pedersen K, Christensen S, Gerdes K. Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Molecular Microbiology 2002, 45(2), 501-510.
• Møller T, Franch T, Udesen C, Gerdes K, Valentin-Hansen P. Spot 42 RNA mediates discoordinate expression of the E. coli galactose operon. Genes and Development 2002, 16(13), 1696-1706.
• Greenfield TJ, Franch T, Gerdes K, Weaver K. Antisense RNA regulation of the par post-segregational killing system: structural analysis and mechanism of binding of the antisense RNA, RNAII and its target, RNAI. Molecular Microbiology 2001, 42, 527-537.
• Christensen S, Mikkelsen M, Pedersen K, Gerdes K. RelE, a global inhibitor of translation, is activated by nutritional stress. Proceedings of the National Academy of Sciences USA 2001, 98, 14328-14333.
• Møller-Jensen J, Franch T, Gerdes K. Temporal translational control by a metastable RNA structure. Journal of Biological Chemistry 2001, 276, 35707-35713.
• Ebersbach G, Gerdes K. The double par locus of virulence factor pB171: Plasmid segregation is correlated with oscillation of ParA. Proceedings of the National Academy of Sciences of the USA 2001, 98, 15078-15083.
• Kristoffersen P, Jensen GB, Gerdes K, Piskur J. Bacterial toxin-antitoxin gene system as containment control in yeast cells. Applied and Environmental Microbiology 2000, 66(12), 5524-5526.
• Gultyaev AP, Franch T, Gerdes K. Coupled nucleotide covariations reveal dynamic RNA interaction patterns. RNA 2000, 6(11), 1483-1491.
• Møller-Jensen J, Jensen RB, Gerdes K. Plasmid and Chromosome Partitioning in Prokaryotes. Trends in Microbiology 2000, 8(7), 313-320.
• Gerdes K, Møller-Jensen J, Jensen RB. Plasmid and chromosome partitioning: surprises from phylogeny. Molecular Microbiology 2000, 37(3), 455-466.
• Greenfield TJ, Ehli E, Kirshenmann T, Franch T, Gerdes K, Weaver KE. The antisense RNA of the par locus of pAD1 regulates the expression of a 33-amino-acid toxic peptide by an unusual mechanism. Molecular Microbiology 2000, 37(3), 652-660.
• Gerdes K. Toxin-Antitoxin Modules May Regulate Synthesis of Macromolecules during Nutritional Stress. Journal of Bacteriology 2000, 182(3), 561-572.
• Franch T, Gerdes K. U-turns and regulatory RNAs. Current Opinion in Microbiology 2000, 3(2), 159-164.
• Franch, T., Michael Petersen, E. Gerhart H. Wagner, Jens Peter Jacobsen, and Gerdes, K. Antisense RNA regulation in prokaryotes: Rapid RNA/RNA interaction facilitated by a general U-turn loop structure.. J. Mol. Biol. 1999, 294, 1115-1125.
• Jensen, R.B., Lurz, R. and Gerdes, K. Mechanism of DNA segregation in prokaryotes: Replicon pairing by parC of plasmid R1.. Proc. Natl. Acad. Sci. USA 1999, 95, 8550-8555.
• Nagel, J. Gultyaev, A.P., Gerdes, K. and Pleij, C.W.A. Metastable structures and refolding kinetics in hok mRNA of plasmid R1. RNA 1999, 5, 1408-1419.
• Pedersen, K. and Gerdes, K. Multiple hok loci in Escherichia coli. Mol. Microbiol. 1999, 1090-1102.
• Franch, T. Thisted, T., and Gerdes, K. 1999. Ribonuclease III Processing of Coaxially Stacked RNA Helices. J. Biol. Chem. 1999, 274, 26572-26578.
• Grønlund, H. and Gerdes, K. Toxin-antitoxin systems homologous to relBE of Escherichia coli plasmid P307 are ubiquitous in prokaryotes. J. Mol. Biol. 1999, 285, 1401-1415.
• Jensen, R.B. and Gerdes, K. Mechanism of DNA segregation in prokaryotes: ParM partitioning protein of plasmid R1 co-localizes with its replicon during the cell cycle.. EMBO J. 1998, 19, 4076-4084.
• Ali, O.M., Franch, T., Gerdes, K., and Pedersen, B.E. Targeting of nucleic acid junctions: addressing an oligodeoxynucleotide with a conjugated intercalator to a branch-point.. Nucl. Acids Res. 1998, 26, 4919-4924.
• Gotfredsen, M and Gerdes, K. The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family. Mol. Microbiol 1998, 29, 1065-1076.
• K. Gerdes,A. P. Gultyaev,T. Franch,K. Pedersen,N. D. Mikkelsen. Antisense RNA-regulated programmed cell death. Annu Rev Genet 1997, 31, 1-31.
• K. Gerdes,J. S. Jacobsen,T. Franch. Plasmid stabilization by post-segregational killing. Genet Eng (N Y) 1997, 19, 49-61.
• T. Thisted,N. S. Sorensen,E. G. Wagner,K. Gerdes. Mechanism of post-segregational killing: Sok antisense RNA interacts with Hok mRNA via its 5'-end single-stranded leader and competes with the 3'-end of Hok mRNA for binding to the mok translational initiation region. EMBO J 1994, 13(8), 1960-8.
• T. Thisted,A. K. Nielsen,K. Gerdes. Mechanism of post-segregational killing: translation of Hok, SrnB and Pnd mRNAs of plasmids R1, F and R483 is activated by 3'-end processing. EMBO J 1994, 13(8), 1950-9.
• K. Gerdes,L. K. Poulsen,T. Thisted,A. K. Nielsen,J. Martinussen,P. H. Andreasen. The hok killer gene family in gram-negative bacteria. New Biol 1990, 2(11), 946-56.
• P. B. Rasmussen,K. Gerdes,S. Molin. Genetic analysis of the parB+ locus of plasmid R1. Mol Gen Genet 1987, 209(1), 122-8.
• K. Gerdes,F. W. Bech,S. T. Jorgensen,A. Lobner-Olesen,P. B. Rasmussen,T. Atlung,L. Boe,O. Karlstrom,S. Molin,K. von Meyenburg. Mechanism of postsegregational killing by the hok gene product of the parB system of plasmid R1 and its homology with the relF gene product of the E. coli relB operon. EMBO J 1986, 5(8), 2023-9.