Birgitta Henriques-Normark Group

 

Birgitta Henriques-Normark is Professor in medical microbial pathogenesis at MTC as well as a Medical Doctor (MD) with speciality in clinical bacteriology.

The main research interest is host-bacterial interactions. This spans many projects, ranging from bacterial regulatory systems to the immune response of the host. Much work is done together with other groups in a larger constellation of researchers to facilitate introduction of new techniques and ideas.

Project Groups Within The Birgitta Henriques-Normark Group

Edmund Loh

Katrin Pütsep

 

Host-pathogen interactions in health and disease

Our research focuses mainly on host-bacterial interactions, with projects ranging from bacterial regulatory systems to innate immune responses in the host. The main research program includes studies on the molecular epidemiology and pathogenesis of pneumococcal infections, from the clinical side to more basic approaches looking at host-pathogen interactions. Also, antibiotic resistance development is targeted.

Streptococcus pneumoniae is a common cause of morbidity and mortality worldwide, killing 1 to 2 million people every year. Despite being devastating pathogens they are also frequent colonizers of the upper respiratory tract of healthy children attending day-care centers. We have studied the molecular epidemiology of invasive pneumococcal disease and found that certain serotypes and clones are more prone to give raise to invasive disease, such as clones of type 1 and 7F. These types are more commonly found among previously healthy individuals. We have also identified novel virulence factors such as a pilus like structure important for adherence, colonization, and virulence, as well as for the inflammatory response. Furthermore we have shown that pneumococci are trapped but not killed by so called neutrophil extracellular traps (NETs). However, the bacteria may free themselves from NETs by using an endonuclease, thereby promoting spread to the lungs and the bloodstream. Recently we have found that of the Toll-like receptors (TLR) 1,2,4,6 and 9, only TLR 9 plays a non-redundant role in pneumococcal infections. Other research includes studies of inhibitors of the type III secretion system in Chlamydia trachomatis, an enzymatic ruler that modulates Lewis antigen glycosylation of Helicobacter pylori lipopolysaccharide during persistent infection, antimicrobial peptides, and invasive Group A streptococcal infections. We will also continue our work on the recently described pilus-like structure and other potential vaccine candidates, as well as on type III secretion inhibitors for drug development.

The work can tentatively be divided into the following areas:


1. The innate immune defense and bacterial infections.
The interaction between the innate immune system and microbial pathogens including for example Toll like receptors, NODs, scavenger receptors and antimicrobial peptides.

2. Streptococcus pneumoniae (pneumococci).
Involves many aspects of this pathogen, ranging from its epidemiology and antibiotic resistance to virulence and pathogenesis aspects and the interaction with the innate immune system.

3. Helicobacter
To understand the interactions with the host and why some strains are more virulent than others.

4. Regulation of virulence genes.
Escherichia coli and Salmonella are the main models to look at gene regulatory mechanisms involved in virulence and adaptation to new environments.

5. Bacterial adhesion organelles.
Studying the biogenesis of adhesion organelles, such as pili and curli. But also their role in disease.

6. Cell wall synthesis.
Includes projects from reageneration of cell wall components and programmed cell death in bacteria to the function and regulation of beta-lactamases.

7. Chlamydia species.
Specifically we are studying inhibitors of the type III secretion system.
To find out more details please have a look at our recent publications.

Research Constellation Host-microbe interactions Publications

Research Constellation Host-microbe interactions Publications (pdf file)

 

Publications - Birgitta Henriques-Normark

Streptococcus pneumoniae senses a human-like sialic acid profile via the response regulator CiaR
Karina Hentrich, Jonas Lofling, Anuj Pathak, Victor Nizet, Ajit Varki, Birgitta Henriques-Normark
Cell Host & Microbe, online 1 September 2016, DOI: http://dx.doi.org/10.1016/j.chom.2016.07.019

Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity.
Xie S, Spelmink L, Codemo M, Subramanian K, Pütsep K, Henriques-Normark B, et al
PLoS ONE 2016 ;11(8):e0160734

Unaltered pneumococcal carriage prevalence due to expansion of non-vaccine types of low invasive potential 8years after vaccine introduction in Stockholm, Sweden.
Lindstrand A, Galanis I, Darenberg J, Morfeldt E, Naucler P, Blennow M, et al
Vaccine 2016 Aug;34(38):4565-71

Pneumococcal meningitis is promoted by single cocci expressing pilus adhesin RrgA.
Iovino F, Hammarlöf D, Garriss G, Brovall S, Nannapaneni P, Henriques-Normark B
J. Clin. Invest. 2016 Aug;126(8):2821-6

The crystal structure of the major pneumococcal autolysin LytA in complex with a large peptidoglycan fragment reveals the pivotal role of glycans for lytic activity.
Sandalova T, Lee M, Henriques-Normark B, Hesek D, Mobashery S, Mellroth P, et al
Mol. Microbiol. 2016 Sep;101(6):954-67

lytA-based identification methods can misidentify Streptococcus pneumoniae.
Simões A, Tavares D, Rolo D, Ardanuy C, Goossens H, Henriques-Normark B, et al
Diagn. Microbiol. Infect. Dis. 2016 Jun;85(2):141-8

Toll-Like Receptor 3/TRIF-Dependent IL-12p70 Secretion Mediated by Streptococcus pneumoniae RNA and Its Priming by Influenza A Virus Coinfection in Human Dendritic Cells.
Spelmink L, Sender V, Hentrich K, Kuri T, Plant L, Henriques-Normark B
MBio 2016 ;7(2):e00168-16

How Does Streptococcus pneumoniae Invade the Brain?
Iovino F, Seinen J, Henriques-Normark B, van Dijl J
Trends Microbiol. 2016 Apr;24(4):307-15

Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm, Sweden.
Galanis I, Lindstrand A, Darenberg J, Browall S, Nannapaneni P, Sjöström K, et al
Eur. Respir. J. 2016 Apr;47(4):1208-18

Variation in Inflammatory Response during Pneumococcal Infection Is Influenced by Host-Pathogen Interactions but Associated with Animal Survival.
Jonczyk M, Escudero L, Sylvius N, Norman M, Henriques-Normark B, Andrew P
Infect. Immun. 2016 Apr;84(4):894-905

Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection.
Dudek M, Puttur F, Arnold-Schrauf C, Kühl A, Holzmann B, Henriques-Normark B, et al
Mucosal Immunol 2016 Sep;9(5):1288-302

Streptococcal M1 Strikes by Neutralizing Cathelicidins.
Henriques-Normark B, Normark S
Cell Host Microbe 2015 Oct;18(4):390-1

BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAMlow CD11bhigh Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming.
Bollampalli V, Harumi Yamashiro L, Feng X, Bierschenk D, Gao Y, Blom H, et al
PLoS Pathog. 2015 Oct;11(10):e1005206

Respiratory viruses associated with community-acquired pneumonia in children: matched case-control study.
Rhedin S, Lindstrand A, Hjelmgren A, Ryd-Rinder M, Öhrmalm L, Tolfvenstam T, et al
Thorax 2015 Sep;70(9):847-53

Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types.
Browall S, Backhaus E, Naucler P, Galanis I, Sjöström K, Karlsson D, et al
Eur. Respir. J. 2014 Dec;44(6):1646-57

Secretion of a pneumococcal type II secretion system pilus correlates with DNA uptake during transformation.
Balaban M, Bättig P, Muschiol S, Tirier S, Wartha F, Normark S, et al
Proc. Natl. Acad. Sci. U.S.A. 2014 Feb;111(7):E758-65

Sinusitis and pneumonia hospitalization after introduction of pneumococcal conjugate vaccine.
Lindstrand A, Bennet R, Galanis I, Blennow M, Ask L, Dennison S, et al
Pediatrics 2014 Dec;134(6):e1528-36

Clinical efficacy of polyspecific intravenous immunoglobulin therapy in patients with streptococcal toxic shock syndrome: a comparative observational study.
Linnér A, Darenberg J, Sjölin J, Henriques-Normark B, Norrby-Teglund A
Clin. Infect. Dis. 2014 Sep;59(6):851-7

Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences.
Nasser W, Beres S, Olsen R, Dean M, Rice K, Long S, et al
Proc. Natl. Acad. Sci. U.S.A. 2014 Apr;111(17):E1768-76

Emergence of hypervirulent mutants resistant to early clearance during systemic serotype 1 pneumococcal infection in mice and humans.
Syk A, Norman M, Fernebro J, Gallotta M, Farmand S, Sandgren A, et al
J. Infect. Dis. 2014 Jul;210(1):4-13

Prevalence of community-acquired bacteraemia in Guinea-Bissau: an observational study.
Isendahl J, Manjuba C, Rodrigues A, Xu W, Henriques-Normark B, Giske C, et al
BMC Infect. Dis. 2014 ;14():3859

Improvement of CRB-65 as a prognostic tool in adult patients with community-acquired pneumonia.
Dwyer R, Hedlund J, Henriques-Normark B, Kalin M
BMJ Open Respir Res 2014 ;1(1):e000038

UlaR activates expression of the ula operon in Streptococcus pneumoniae in the presence of ascorbic acid.
Afzal M, Shafeeq S, Henriques-Normark B, Kuipers O
Microbiology (Reading, Engl.) 2015 Jan;161(Pt 1):41-9

European enhanced surveillance of invasive pneumococcal disease in 2010: data from 26 European countries in the post-heptavalent conjugate vaccine era.
Navarro Torné A, Dias J, Quinten C, Hruba F, Busana M, Lopalco P, et al
Vaccine 2014 Jun;32(29):3644-50

A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development.
Sanderson-Smith M, De Oliveira D, Guglielmini J, McMillan D, Vu T, Holien J, et al
J. Infect. Dis. 2014 Oct;210(8):1325-38

Structural and functional insights into peptidoglycan access for the lytic amidase LytA of Streptococcus pneumoniae.
Mellroth P, Sandalova T, Kikhney A, Vilaplana F, Hesek D, Lee M, et al
MBio 2014 ;5(1):e01120-13

The basic keratin 10-binding domain of the virulence-associated pneumococcal serine-rich protein PsrP adopts a novel MSCRAMM fold.
Schulte T, Löfling J, Mikaelsson C, Kikhney A, Hentrich K, Diamante A, et al
Open Biol 2014 ;4():130090

Clinical utility of PCR for common viruses in acute respiratory illness.
Rhedin S, Lindstrand A, Rotzén-Östlund M, Tolfvenstam T, Ohrmalm L, Rinder M, et al
Pediatrics 2014 Mar;133(3):e538-45

Focal targeting by human β-defensin 2 disrupts localized virulence factor assembly sites in Enterococcus faecalis.
Kandaswamy K, Liew T, Wang C, Huston-Warren E, Meyer-Hoffert U, Hultenby K, et al
Proc. Natl. Acad. Sci. U.S.A. 2013 Dec;110(50):20230-5

Adult zebrafish model for pneumococcal pathogenesis.
Saralahti A, Piippo H, Parikka M, Henriques-Normark B, Rämet M, Rounioja S
Dev. Comp. Immunol. 2014 Feb;42(2):345-53

Intraclonal variations among Streptococcus pneumoniae isolates influence the likelihood of invasive disease in children.
Browall S, Norman M, Tångrot J, Galanis I, Sjöström K, Dagerhamn J, et al
J. Infect. Dis. 2014 Feb;209(3):377-88

Dominant role of nucleotide substitution in the diversification of serotype 3 pneumococci over decades and during a single infection.
Croucher N, Mitchell A, Gould K, Inverarity D, Barquist L, Feltwell T, et al
PLoS Genet. 2013 ;9(10):e1003868

Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae.
Olliver M, Spelmink L, Hiew J, Meyer-Hoffert U, Henriques-Normark B, Bergman P
J. Infect. Dis. 2013 Nov;208(9):1474-81

 

Older Publications

Publications 2007-2011

Publications 2006-2007 (Pdf file, 41 Kb)

Publications 1987-2005

Publication 1987-2005 (Pdf file, 59 Kb)

Group Members

Professor/senior physician

Birgitta Henriques Normark

Phone: 08-517 712 16
Organizational unit: Birgitta Henriques Normark group
E-mail: Birgitta.Henriques@ki.se

Anna SykGraduate Student, Research engineer
Anuj PathakPostdoc
Birgitta Henriques NormarkProfessor/senior physician
Edmund LohAssistant professor
Elisabeth ReithuberPhD student, Graduate Student
Federico IovinoPostdoc
Genevieve GarrissPostdoctoral researcher, Marie Curie
Georgios SotiriouAssistant professor
Hannes EichnerPhD student, Graduate Student
Jens Karlsson R&D trainee, Graduate Student
John BossLaboratory technician
Karina HentrichPhD student, Graduate Student
Karthik SubramanianPostdoc
Katrin PütsepSenior Lecturer, Senior researcher
Laura SpelminkPhD student, Graduate Student
Maria CarlssonCoordinator
Marie-Stephanie aschtgenAssociated, Postdoc
Mario CodemoPhD student, Graduate Student
Martin NormanPhD student
Nils BlockGraduate Student
Peter MellrothSenior researcher
Priyanka NannapaneniPostdoc
Sandra MuschiolSenior lab manager
Sarah BrovallAssociated
Staffan NormarkProfessor, senior
Stefanie Prast-NielsenAssociated
Stephen PietermanAssociated
Susan FarmandAssociated
Vicky SenderPostdoc
Vitor OliveiraPhD student, Graduate Student

Research assistant

Xinyi Yang

E-mail: xinyi.yang@ki.se