Søren Molin

Technical University of Denmark

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Helle Krogh Johansen

Rigshospitalet

114

Michael Givskov

University of Copenhagen

Niels Høiby

Copenhagen University Hospital

Rasmus L. Marvig

Rigshospitalet

Janus A. J. Haagensen

Technical University of Denmark

Claus Sternberg

Technical University of Denmark

Lea M. Sommer

Klinik und Poliklinik für Psychiatrie und Psychotherapie

Tim Tolker‐Nielsen

University of Copenhagen

Leo Eberl

University of Zurich

Lars Jelsbak

Technical University of Denmark

Cooperative Institutions

Technical University of Denmark

265

University of Copenhagen

179

Rigshospitalet

103

Copenhagen University Hospital

Novo Nordisk Foundation

Consejo Superior de Investigaciones Científicas

Centre National de la Recherche Scientifique

Aarhus University

Ørsted (Denmark)

Czech Academy of Sciences, Institute of Microbiology

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N -Acyl-l-Homoserine Lactone Autoinducers Control Production of an Extracellular Lipopeptide Biosurfactant Required for Swarming Motility of Serratia liquefaciens MG1

Journal of Bacteriology (1998)

Peter W. Lindum Uffer Anthoni Camilla Christophersen Leo Eberl Søren Molin

A nonswarming Serratia liquefaciens mutant deficient in serrawettin W2 production was constructed by transposon mutagenesis. Sequence homology indicated that insertion had occurred in geneswrA, which encodes a putative peptide synthetase. Expression of swrA is controlled by quorum sensing.

Lipopeptide

Autoinducer

Swarming motility

Serratia

Swarming (honey bee)

Homoserine

10.1128/.180.23.6384-6388.1998

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Citations (13)

Development of antibiotic resistance reveals diverse evolutionary pathways to face the complex and dynamic environment of a long-term treated patient

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Claudia A. Colque Pablo E. Tomatis Andrea G. Albarracín Orio Gina Dotta Diego M. Moreno

ABSTRACT Antibiotic resistance development has been studied using approaches that range from laboratory experimental evolution, surveillance and epidemiology, to clinical isolate sequencing. However, evolutionary trajectories depend on the environment in which selection takes place, compelling to address evolutionary analyses in antibiotic-treated patients, to embrace the whole inherent environmental complexities as well as their dynamics over time. Herein, we address the complexity of the bacterial adaptive response to changing antibiotic selective pressures by studying the long-term in-patient evolution of a broad diversity of β-lactam resistant Pseudomonas aeruginosa clones. By using mutational and ultra-deep amplicon sequencing, we analyzed multiple generations of a P. aeruginosa hypermutator strain persisting for more than 26 years of chronic infection in the airways of a cystic fibrosis (CF) patient. We identified the accumulation of multiple alterations targeting the chromosomally encoded class C β-lactamase ( bla PDC ), providing structural and functional protein changes that resulted in a continuous enhancement of its catalytic efficiency and high level of cephalosporin resistance. This evolution was linked to the persistent treatment with ceftazidime, which we demonstrate selected for variants with robust catalytic activity against this expanded-spectrum cephalosporin. Surprisingly, “a gain of function” of collateral resistance towards ceftolozane, a more recently introduced cephalosporin that was not prescribed to this patient, was also observed and the biochemical basis of this cross-resistance phenomenon was elucidated. This work unveils the diversity of evolutionary trajectories driven by bacteria in the natural CF environmental setting, towards a multidrug resistant phenotype after years of antibiotic treatment against a formidable pathogen.

Evolutionary Dynamics

10.1101/2021.05.14.444257

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Conditional-Suicide Containment System for Bacteria Which Mineralize Aromatics

Applied and Environmental Microbiology (1991)

Asunción Contreras Søren Molin Juan L. Ramos

A model conditional-suicide system to control genetically engineered microorganisms able to degrade substituted benzoates is reported. The system is based on two elements. One element consists of a fusion between the promoter of the Pseudomonas putida TOL plasmid-encoded meta -cleavage pathway operon (P m ) and the lacI gene encoding Lac repressor plus xylS , coding for the positive regulator of P m . The other element carries a fusion between the P tac promoter and the gef gene, which encodes a killing function. In the presence of XylS effectors, LacI protein is synthesized, preventing the expression of the killing function. In the absence of effectors, expression of the P tac :: gef cassette is no longer prevented and a high rate of cell killing is observed. The substitution of XylS for XylSthr45, a mutant regulator with altered effector specificity and increased affinity for benzoates, allows the control of populations able to degrade a wider range of benzoates at micromolar substrate concentrations. Given the wide effector specificity of the key regulators, the wild-type and mutant XylS proteins, the system should allow the control of populations able to metabolize benzoate; methyl-, dimethyl-, chloro-, dichloro-, ethyl-, and methoxybenzoates; salicylate; and methyl- and chlorosalicylates. A small population of genetically engineered microorganisms became Gef resistant; however, the mechanism of such survival remains unknown.

Pseudomonas putida

Lac repressor

TetR

10.1128/aem.57.5.1504-1508.1991

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Citations (94)

Convergent transcription interferes with expression of the copy number control gene, copA , from plasmid R1

The EMBO Journal (1982)

Peter Stougaard Janice Light Søren Molin

Reprint

10.1002/j.1460-2075.1982.tb01168.x

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Citations (38)

Ltx 109 Is a Novel Antimicrobial Agent with Marked Activity against Bacterial Biofilms

Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy (2009)

R. Jensen Anders Folkesson Søren Molin Wenche Stensen John S. Svendsen

Anti-Infective Agents

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We wish more professional debate about the bibliometric research indicators

Ugeskrift for Læger (2010)

Jørgen Søndergaard Poul Erik Mouritzen Søren‐Peter Olesen Søren Molin Hans Fink

Wish

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Biofilm Formation of Legionella pneumophila in Complex Medium under Static and Dynamic Flow Conditions

ASM Press eBooks (2014)

Jörg Mämpel Thomas Spirig Stefan Weber Janus A. J. Haagensen Søren Molin

This chapter analyzes biofilm formation of Legionella pneumophila in rich medium which supports extracellular proliferation of the bacteria. To investigate biofilm formation of Legionella under static conditions, a 1:1 mixture of L. pneumophila labeled with the fluorescent proteins EGFP or DsRed-Express was inoculated in a glass-bottom 35-mm petri dish. Biofilm formation was analyzed with an inverted confocal microscope (Axiovert 200M, 100 X oil objective Plan Neofluar; Zeiss). Biofilm formation of L. pneumophila in rich medium was also quantified by crystal violet staining in upright polystyrene microtiter plates or on polystyrene pins of "inverse" lids under static (no medium exchange) or quasi-static conditions (medium replaced twice a day). The L. pneumophila fliA mutant strain reproducibly accumulated 30% less biomass within 5 days, demonstrating that bacterial factors contribute to biofilm formation. It is noteworthy that mutants lacking rpoS or letA, both of which are required for the expression of transmissive (virulence) traits of L. pneumophila, were not affected in biofilm formation. A continuous-flow chamber system was set up to further test the hypothesis that plank-tonic cells are crucial for biofilm formation on surfaces and to noninvasively monitor in real-time the adherence and biofilm formation of L. pneumophila under dynamic flow conditions.

Legionella

Crystal violet

Petri dish

Polystyrene

10.1128/9781555815660.ch93

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Estimation of Growth Rates of Escherichia coli BJ4 in Streptomycin-Treated and Previously Germfree Mice by In Situ rRNA Hybridization

Clinical and Diagnostic Laboratory Immunology (1999)

Camilla U. Rang Tine Rask Licht Tore Midtvedt Patricia L. Conway Lin Chao

ABSTRACT The growth physiology of Escherichia coli during colonization of the intestinal tract was studied with four animal models: the streptomycin-treated mouse carrying a reduced microflora, the monoassociated mouse with no other microflora than the introduced strain, the conventionalized streptomycin-treated mouse, and the conventionalized monoassociated mouse harboring a full microflora. A 23S rRNA fluorescent oligonucleotide probe was used for hybridization to whole E. coli cells fixed directly after being taken from the animals, and the respective growth rates of E. coli BJ4 in the four animal models were estimated by correlating the cellular concentrations of ribosomes with the growth rate of the strain. The growth rates thus estimated from the ribosomal content of E. coli BJ4 in vivo did not differ in the streptomycin-treated and the monoassociated mice. After conventionalization there was a slight decrease of the bacterial growth rates in both animal models.

Strain (injury)

23S ribosomal RNA

10.1128/cdli.6.3.434-436.1999

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Citations (59)

A dual role of extracellular DNA during biofilm formation of Neisseria meningitidis

Molecular Microbiology (2010)

Martin Lappann Heike Claus Tessa van Alen Morten Harmsen Johannes Elias

Major pathogenic clonal complexes (cc) of Neisseria meningitidis differ substantially in their point prevalence among healthy carriers. We show that frequently carried pathogenic cc (e.g. sequence type ST-41/44 cc and ST-32 cc) depend on extracellular DNA (eDNA) to initiate in vitro biofilm formation, whereas biofilm formation of cc with low point prevalence (ST-8 cc and ST-11 cc) was eDNA-independent. For initial biofilm formation, a ST-32 cc type strain, but not a ST-11 type strain, utilized eDNA. The release of eDNA was mediated by lytic transglycosylase and cytoplasmic N-acetylmuramyl-L-alanine amidase genes. In late biofilms, outer membrane phospholipase A-dependent autolysis, which was observed in most cc, but not in ST-8 and ST-11 strains, was required for shear force resistance of microcolonies. Taken together, N. meningitidis evolved two different biofilm formation strategies, an eDNA-dependent one yielding shear force resistant microcolonies, and an eDNA-independent one. Based on the experimental findings and previous epidemiological observations, we hypothesize that most meningococcal cc display a settler phenotype, which is eDNA-dependent and results in a stable interaction with the host. On the contrary, spreaders (ST-11 and ST-8 cc) are unable to use eDNA for biofilm formation and might compensate for poor colonization properties by high transmission rates.

Strain (injury)

10.1111/j.1365-2958.2010.07054.x

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Citations (142)

Characterization of Acinetobacter sp. C6 and Pseudomonas aeruginosa biofilms degrading toluene derivatives

Isabelle George Janus A. J. Haagensen Søren Molin Vı́ctor de Lorenzo

Pseudomonadales

Neisseriaceae

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