Ute Römling Group


Multicellular behavior in Enterobacteriaceae

Multicellular behavior (biofilm formation) is found in almost all prokaryotes. It is generally considered as a survival mechanism, which is induced upon nutrient starvation. In the clinical setting, bacteria, which build up biofilms, cause persistent infections and colonize indwelling devices. Members of the Enterobacteriaceae, among them Salmonella typhimurium, Escherichia coli and others, cause a high percentage of nosocomial and community acquired infections whereby some are biofilm-related infections. In addition, transmission, colonization and persistence of the organisms include a biofilm component

Our model system is the rdar morphotype, bacterial cells, which express curli fimbriae and cellulose. This morphotype is commonly expressed by S. typhimurium and Salmonella enteritidis as well as commensal E. coli and certain E. coli pathovars.

Our special interest is to study the regulatory network leading to rdar morphotype expression in Enterobacteriaceae. Our research focuses on cyclic di-GMP, a novel secondary messenger in Bacteria, which is regulating rdar morphotype expression on several levels.

In addition, we investigate the role of extracellular matrix components in bacteria-host interactions.

Pseudomonas aeruginosa infections in cystic fibrosis

Cystic fibrosis (CF) is the most common autosomal recessive disorder of Caucasians, which is caused by the impaired function of the cystic fibrosis transmembrane conductance regulator (CFTR). P. aeruginosa plays a predominant role with up to 90% of colonized individuals in certain patient populations. Antibiotic therapy is CF patients is not effective, since the bacteria grow in antibiotic resistant biofilms.

We have identified a P. aeruginosa clone present in CF patients world-wide as well as in the aquatic habitat.

We are interested in the mechanisms of adaptation of this and other P. aeruginosa clones to the CF lung habitat. Our research includes the study of genetic variations in CF isolates, comparative protein expression studies of isolates, development of a model for biofilm formation in the CF lung and study of the mechanisms of environmental survival and persistence.

We can offer Master thesis work to highly interested and qualified applicants. Please ask for possibilities for a project for post-graduate and post-doctoral studies.


Vetenskapsrådet - Natural Sciences
Carl Trygger Foundation
Petrus and Augusta Hedlund Foundation
Karolinska Institutet


Multicellular morphotype and biofilm behavior in Salmonella typhimurium

Multicellular behavior in bacteria has impact for the survival of cells in the natural environments, but is also causing disease in medical settings. A multicellular morphotype which displays also biofilm behavior is widely expressed among natural isolates of Escherichia coli and Salmonella spp.

We are studying the occurrence of multicellular behavior in natural isolates of E. coli and Salmonella spp., its regulation and its role in the environment and in bacterial-host interactions.

Extracellular matrix components

The multicellular morphotype in Salmonella typhimurium is characterized by the expression of an extracellular matrix composed of among other components, thin aggregative fimbriae and the exopolysaccharide cellulose. Cellulose expression is activated by the novel secondary messenger cyclic di-GMP.

Regulation of the rdar morphotype

The multicellular morphotype is controlled by the expression of the transcriptional regulator CsgD a major regulator of multicellular behavior in S. Typhimurium. CsgD expression is highly regulated by a variety of environmental conditions and global regulatory proteins.

Most importantly, the novel secondary messenger cyclic di-GMP is affecting CsgD expression. At least 6 di-guanylate cyclases and phosphodiesterases are regulating CsgD expression. In addition, CsgD regulates the di-guanylate cyclase AdrA which is required for the activation of cellulose biosynthesis.

Currently, we are investigating the molecular mechanisms leading to CsgD expression by c-di-GMP signaling.

As conclusion the expression of the multicellular morphotype consists of a complex regulatory network that is only partially explored.

Cyclic di-GMP signaling

Cyclic di-GMP is a novel secondary signaling molecule in Bacteria. It was originally discovered by the group around Moshe Benziman as an allosteric activator of cellulose synthase in Gluconacetobacter xylinus 20 years ago.

In 2004, our group and, independently, the group of Urs Jenal and Andrew Camilli, demonstrated that cyclic di-GMP is a novel secondary messenger in Bacteria. Since then, phenotypes mostly related to biofilm formation, but also other phenotypes such as virulence are discovered to be cyclic di-GMP dependent in many bacteria.

Currently, we are studying the role of c-di-GMP signaling in the disease process in S. Typhimurium

Role of biofilm formation in bacterial-host interaction

The rdar morphotype is expressed not only by pathogenic S. Typhimurium isolates, but also by commensal E. coli isolates.

Recently, we investigated to role of the extracellular matrix components in bacterial-host interaction. Expression of curli fimbriae stimulated adhesion, invasion and IL-8 production, whereas co-expression of cellulose inhibited adhesion, invasion and IL-8 production.


The Endurance of Microbiology: An Interview with Mike Jetten, Mark Martin, Ute Römling, and Victor Torres.
Jetten M, Martin M, Römling U, Torres V
Trends Microbiol. 2016 May;24(5):319-23

Amyloid formation: functional friend or fearful foe?
Bergman P, Roan N, Römling U, Bevins C, Münch J
J. Intern. Med. 2016 Aug;280(2):139-52

Protein homeostasis-more than resisting a hot bath.
Lee C, Wigren E, Lünsdorf H, Römling U
Curr. Opin. Microbiol. 2016 Apr;30():147-54

Escherichia coli: an old friend with new tidings.
Vila J, Sáez-López E, Johnson J, Römling U, Dobrindt U, Cantón R, et al
FEMS Microbiol. Rev. 2016 Mar;():

Bacterial cellulose biosynthesis: diversity of operons, subunits, products, and functions.
Römling U, Galperin M
Trends Microbiol. 2015 Sep;23(9):545-57

Small molecules with big effects: Cyclic di-GMP-mediated stimulation of cellulose production by the amino acid ʟ-arginine.
Römling U
Sci Signal 2015 Jun;8(380):fs12

A novel protein quality control mechanism contributes to heat shock resistance of worldwide-distributed Pseudomonas aeruginosa clone C strains.
Lee C, Wigren E, Trček J, Peters V, Kim J, Hasni M, et al
Environ. Microbiol. 2015 Nov;17(11):4511-26

Dissecting the cyclic di-guanylate monophosphate signalling network regulating motility in Salmonella enterica serovar Typhimurium.
Le Guyon S, Simm R, Rehn M, Römling U
Environ. Microbiol. 2015 Apr;17(4):1310-20

Biofilm formation by enteric pathogens and its role in plant colonization and persistence.
Yaron S, Römling U
Microb Biotechnol 2014 Nov;7(6):496-516

Modulation of biofilm-formation in Salmonella enterica serovar Typhimurium by the periplasmic DsbA/DsbB oxidoreductase system requires the GGDEF-EAL domain protein STM3615.
Anwar N, Rouf S, Römling U, Rhen M
PLoS ONE 2014 ;9(8):e106095

GIL, a new c-di-GMP-binding protein domain involved in regulation of cellulose synthesis in enterobacteria.
Fang X, Ahmad I, Blanka A, Schottkowski M, Cimdins A, Galperin M, et al
Mol. Microbiol. 2014 Aug;93(3):439-52

Dissecting the cyclic di-guanylate monophosphate signalling network regulating motility in Salmonella enterica serovar Typhimurium.
Le Guyon S, Simm R, Rehn M, Römling U
Environ. Microbiol. 2015 Apr;17(4):1310-20

Microbial biofilm formation: a need to act.
Römling U, Kjelleberg S, Normark S, Nyman L, Uhlin B, Åkerlund B
J. Intern. Med. 2014 Aug;276(2):98-110

Draft Genome Sequence of Pseudomonas aeruginosa SG17M, an Environmental Isolate Belonging to Clone C, Prevalent in Patients and Aquatic Habitats.
Lee C, Peters V, Melefors O, Römling U
Genome Announc 2014 Mar;2(2):

Characterization of biofilm formation and the role of BCR1 in clinical isolates of Candida parapsilosis.
Pannanusorn S, Ramírez-Zavala B, Lünsdorf H, Agerberth B, Morschhäuser J, Römling U
Eukaryotic Cell 2014 Apr;13(4):438-51

Finally! The structural secrets of a HD-GYP phosphodiesterase revealed.
Wigren E, Liang Z, Römling U
Mol. Microbiol. 2014 Jan;91(1):1-5

The EAL-like protein STM1697 regulates virulence phenotypes, motility and biofilm formation in Salmonella typhimurium.
Ahmad I, Wigren E, Le Guyon S, Vekkeli S, Blanka A, El Mouali Y, et al
Mol. Microbiol. 2013 Dec;90(6):1216-32

Control of pathogen growth and biofilm formation using a urinary catheter that releases antimicrobial nitrogen oxides.
Kishikawa H, Ebberyd A, Römling U, Brauner A, Lüthje P, Lundberg J, et al
Free Radic. Biol. Med. 2013 Dec;65():1257-64

Microbiology: bacterial communities as capitalist economies.
Römling U
Nature 2013 May;497(7449):321-2

Prevalence of biofilm formation in clinical isolates of Candida species causing bloodstream infection.
Pannanusorn S, Fernandez V, Römling U
Mycoses 2013 May;56(3):264-72

Cyclic di-GMP: the first 25 years of a universal bacterial second messenger.
Römling U, Galperin M, Gomelsky M
Microbiol. Mol. Biol. Rev. 2013 Mar;77(1):1-52

Biofilm infections, their resilience to therapy and innovative treatment strategies.
Römling U, Balsalobre C
J. Intern. Med. 2012 Dec;272(6):541-61

Cyclic di-GMP, an established secondary messenger still speeding up.
Römling U
Environ. Microbiol. 2012 Aug;14(8):1817-29

Cyclic di-GMP, an established secondary messenger still speeding up.
Römling U
Environ. Microbiol. 2012 Aug;14(8):1817-29

Hfq and Hfq-dependent small RNAs are major contributors to multicellular development in Salmonella enterica serovar Typhimurium.
Monteiro C, Papenfort K, Hentrich K, Ahmad I, Le Guyon S, Reimann R, et al
RNA Biol 2012 Apr;9(4):489-502

Complex c-di-GMP signaling networks mediate transition between virulence properties and biofilm formation in Salmonella enterica serovar Typhimurium.
Ahmad I, Lamprokostopoulou A, Le Guyon S, Streck E, Barthel M, Peters V, et al
PLoS ONE 2011 ;6(12):e28351

Regulation of biofilm components in Salmonella enterica serovar Typhimurium by lytic transglycosylases involved in cell wall turnover.
Monteiro C, Fang X, Ahmad I, Gomelsky M, Römling U
J. Bacteriol. 2011 Dec;193(23):6443-51

Pyrosequencing of a hypervariable region in the internal transcribed spacer 2 to identify clinical yeast isolates.
Pannanusorn S, Elings M, Römling U, Fernandez V
Mycoses 2012 Mar;55(2):172-80

Opposing contributions of polynucleotide phosphorylase and the membrane protein NlpI to biofilm formation by Salmonella enterica serovar Typhimurium.
Rouf S, Ahmad I, Anwar N, Vodnala S, Kader A, Römling U, et al
J. Bacteriol. 2011 Jan;193(2):580-2

Virulence characteristics of translocating Escherichia coli and the interleukin-8 response to infection.
Ramos N, Lamprokostopoulou A, Chapman T, Chin J, Römling U, Brauner A, et al
Microb. Pathog. 2011 Feb;50(2):81-6

A 96-well-plate-based optical method for the quantitative and qualitative evaluation of Pseudomonas aeruginosa biofilm formation and its application to susceptibility testing.
Müsken M, Di Fiore S, Römling U, Häussler S
Nat Protoc 2010 Aug;5(8):1460-9

Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37.
Kai-Larsen Y, Lüthje P, Chromek M, Peters V, Wang X, Holm A, et al
PLoS Pathog. 2010 Jul;6(7):e1001010

Unphosphorylated CsgD controls biofilm formation in Salmonella enterica serovar Typhimurium.
Zakikhany K, Harrington C, Nimtz M, Hinton J, Römling U
Mol. Microbiol. 2010 Aug;77(3):771-86

Two antisense RNAs target the transcriptional regulator CsgD to inhibit curli synthesis.
Holmqvist E, Reimegård J, Sterk M, Grantcharova N, Römling U, Wagner E
EMBO J. 2010 Jun;29(11):1840-50

Human cathelicidin peptide LL37 inhibits both attachment capability and biofilm formation of Staphylococcus epidermidis.
Hell E, Giske C, Nelson A, Römling U, Marchini G
Lett. Appl. Microbiol. 2010 Feb;50(2):211-5

Earlier Publications

Publications 2003-2009 (pdf)

Publications 1989-2001 (pdf file) (Pdf file, 78 Kb)


ESCMID (European Society of Clinical Microbiology and Infectious Diseases)

Young Investigator Award for Research in Clinical Microbiology and Infectious Diseases 2000

Sir Hans Krebs-Preis 1997 der Gesellschaft der Freunde der Medizinischen Hochschule e.V.

Review Articles

Review Articles (pdf file) (Pdf file, 43 Kb)

Book Contributions

Book Contributions (pdf file) (Pdf file, 43 Kb)


Ongoing Collaborations
Within the Karolinska Institutet

  • Birgitta Agerberth
  • Annelie Brauner
  • Ylva Lindquist
  • Mikael Rhen

Within Sweden

  • Sun Nyunt Wai, University of Umeå
  • Gerhard Wagner, Uppsala University


  • Gerd Döring, University of Tubingen, Germany
  • Mark Gomelsky, University of Wyoming, USA
  • Susanne Haeussler, Helmholtz Center of Infection Biology, Braunschweig, Germany
  • Wolf-Dieter Hardt, University of Zurich, Switzerland
  • Heinrich Lunsdorf, Helmholtz Center of Infection Biology, Braunschweig, Germany
  • Manfred Nimtz, Helmholtz Center of Infection Biology, Braunschweig, Germany
  • Jörg Vogel, Max Planck Institute for Infection Biology, Berlin, Germany

Group Members


Ute Römling

Phone: 08-524 873 19
Organizational unit: Ute Römling group
E-mail: Ute.Romling@ki.se

Annika CimdinsPostdoc
Changhan LeeAssociated
Fengyang LiGraduate Student
Linnea GustafssonAssociated
Shady KamalPhD student, Graduate Student
Stefanie SperleinAssociated
Sulman ShafeeqPostdoc
Ute RömlingProfessor
Ying LiuResearch assistant


Ute Römling Group alumni


Srisuda Pannanusorn successfully defended her thesis on the 6th of September, 2013.

Srisuda Pannanusorn discusses her thesisSrisuda has worked on the characterization of biofilm formation in Candida spp bloodstream isolates collected during one year in Sweden. In addition, Srisuda has characterized the biofilm formation in clinical isolates of Candida parapsilosis and investigated the role of the biofilm regulator Bcr1 in these isolates. The opponent  was Geraldine Butler from the University College Dublin, Ireland and the examination committee consisted of Jan Sjölin, Uppsala University; Erja Chryssanthou, Karolinska Institutet and Volkan Özenci, Karolinska Institutet.

You can find the thesis of Srisuda Pannanusorn in the Open Archive of the Karolinska Institutet’s library here:

Srisuda Pannanusorn thesis