Birgitta Henriques-Normark Group

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.

Picture of Birgitta Henriques- Normark group in front of a building

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

Project Groups 

Jan-Ingmar Flock
Edmund Loh

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.

Awards and Prizes

  • Appointed Wallenberg Clinical Scholars 2017
  • Elected Member of the American Academy of Microbiology 2015
  • Elected Member of the European Academy of Microbiology 2013

Group Members

Associated Members

Katrin Pütsep

Research Constellation Host-microbe interactions Publications

Research Constellation Host-microbe interactions Publications (pdf file)

Publications

The Role of Microglia in Bacterial Meningitis: Inflammatory Response, Experimental Models and New Neuroprotective Therapeutic Strategies.
Thorsdottir S, Henriques-Normark B, Iovino F
Front Microbiol 2019 ;10():576

IVIS Spectrum CT to Image the Progression of Pneumococcal Infections In Vivo.
Sierakowiak A, Henriques-Normark B, Iovino F
Methods Mol Biol 2019 ;1968():195-202

In Vivo Mouse Models to Study Pneumococcal Host Interaction and Invasive Pneumococcal Disease.
Iovino F, Sender V, Henriques-Normark B
Methods Mol Biol 2019 ;1968():173-181

High-Resolution and Super-Resolution Immunofluorescent Microscopy Ex Vivo to Study Pneumococcal Interactions with the Host.
Iovino F, Henriques-Normark B
Methods Mol Biol 2019 ;1968():53-59

Immunofluorescent Staining and High-Resolution Microscopy to Study the Pneumococcal Cell.
Iovino F, Henriques-Normark B
Methods Mol Biol 2019 ;1968():35-39

Luminescent CeO2:Eu3+ nanocrystals for robust in situ H2O2 real-time detection in bacterial cell cultures.
Henning DF, Merkl P, Yun C, Iovino F, Xie L, Mouzourakis E, et al
Biosens Bioelectron 2019 May;132():286-293

Gram-Positive Type IV Pili and Competence.
Muschiol S, Aschtgen MS, Nannapaneni P, Henriques-Normark B
Microbiol Spectr 2019 01;7(1):

Pathogenesis and prevention of risk of cardiovascular events in patients with pneumococcal community-acquired pneumonia.
Feldman C, Normark S, Henriques-Normark B, Anderson R
J Intern Med 2019 06;285(6):635-652

Pneumolysin binds to the mannose receptor C type 1 (MRC-1) leading to anti-inflammatory responses and enhanced pneumococcal survival.
Subramanian K, Neill DR, Malak HA, Spelmink L, Khandaker S, Dalla Libera Marchiori G, et al
Nat Microbiol 2019 01;4(1):62-70

Eosinophilia and reduced STAT3 signaling affect neutrophil cell death in autosomal-dominant Hyper-IgE syndrome.
Farmand S, Kremer B, Häffner M, Pütsep K, Bergman P, Sundin M, et al
Eur J Immunol 2018 12;48(12):1975-1988

Aetiology of lower respiratory tract infection in adults in primary care: a prospective study in 11 European countries.
Ieven M, Coenen S, Loens K, Lammens C, Coenjaerts F, Vanderstraeten A, et al
Clin Microbiol Infect 2018 Nov;24(11):1158-1163

Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification.
Pathak A, Bergstrand J, Sender V, Spelmink L, Aschtgen MS, Muschiol S, et al
Nat Commun 2018 08;9(1):3398

Clinical relevance of bacterial resistance in lower respiratory tract infection in primary care: secondary analysis of a multicentre European trial.
Teepe J, Broekhuizen BD, Goossens H, Hordijk PM, Loens K, Lammens C, et al
Br J Gen Pract 2018 Sep;68(674):e627-e632

Receptor Blockade: A Novel Approach to Protect the Brain From Pneumococcal Invasion.
Iovino F, Thorsdottir S, Henriques-Normark B
J Infect Dis 2018 07;218(3):476-484

Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses.
Codemo M, Muschiol S, Iovino F, Nannapaneni P, Plant L, Wai SN, et al
mBio 2018 04;9(2):

Aetiology of lower respiratory tract infection in adults in primary care: a prospective study in 11 European countries.
Ieven M, Coenen S, Loens K, Lammens C, Coenjaerts F, Vanderstraeten A, et al
Clin Microbiol Infect 2018 Nov;24(11):1158-1163

Detection of human disease conditions by single-cell morpho-rheological phenotyping of blood.
Toepfner N, Herold C, Otto O, Rosendahl P, Jacobi A, Kräter M, et al
Elife 2018 01;7():

Separation of pathogenic bacteria by chain length.
Beech JP, Ho BD, Garriss G, Oliveira V, Henriques-Normark B, Tegenfeldt JO
Anal Chim Acta 2018 Feb;1000():223-231

Comparison of the Impact of Pneumococcal Conjugate Vaccine 10 or Pneumococcal Conjugate Vaccine 13 on Invasive Pneumococcal Disease in Equivalent Populations.
Naucler P, Galanis I, Morfeldt E, Darenberg J, Örtqvist Å, Henriques-Normark B
Clin Infect Dis 2017 11;65(11):1780-1789

Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study.
Savulescu C, Krizova P, Lepoutre A, Mereckiene J, Vestrheim DF, Ciruela P, et al
Lancet Respir Med 2017 08;5(8):648-656

Analysis of IAV Replication and Co-infection Dynamics by a Versatile RNA Viral Genome Labeling Method.
Dou D, Hernández-Neuta I, Wang H, Östbye H, Qian X, Thiele S, et al
Cell Rep 2017 07;20(1):251-263

Structure of the competence pilus major pilin ComGC in Streptococcus pneumoniae.
Muschiol S, Erlendsson S, Aschtgen MS, Oliveira V, Schmieder P, de Lichtenberg C, et al
J Biol Chem 2017 08;292(34):14134-14146

pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion
Federico Iovino, Joo-Yeon Engelen-Lee, Matthijs Brouwer, Diederik van de Beek, Arie van der Ende, Merche Valls Seron, Peter Mellroth, Sandra Muschiol, Jan Bergstrand, Jerker Widengren, View ORCID ProfileBirgitta Henriques-Normark
JEM DOI: 10.1084/jem.20161668 | Published May 17, 2017

Widespread and Indiscriminate Nanosilver Use: Genuine Potential for Microbial Resistance.
Gunawan C, Marquis CP, Amal R, Sotiriou GA, Rice SA, Harry EJ
ACS Nano 2017 04;11(4):3438-3445

The Pneumocell-study: Vaccination of IgG1- and IgG2-deficient patients with Prevnar13.
Zangenah S, Björkhem-Bergman L, Norlin AC, Hansen S, Lindqvist L, Henriques-Normark B, et al
Vaccine 2017 05;35(20):2654-2660

Vitamin D Promotes Pneumococcal Killing and Modulates Inflammatory Responses in Primary Human Neutrophils.
Subramanian K, Bergman P, Henriques-Normark B
J Innate Immun 2017 ;9(4):375-386

Coeliac disease and invasive pneumococcal disease: a population-based cohort study.
Röckert Tjernberg A, Bonnedahl J, Inghammar M, Egesten A, Kahlmeter G, Nauclér P, et al
Epidemiol Infect 2017 04;145(6):1203-1209

N-acetylglucosamine-Mediated Expression of nagA and nagB in Streptococcus pneumoniae.
Afzal M, Shafeeq S, Manzoor I, Henriques-Normark B, Kuipers OP
Front Cell Infect Microbiol 2016 ;6():158

Pneumococcal Carriage in Children under Five Years in Uganda-Will Present Pneumococcal Conjugate Vaccines Be Appropriate?
Lindstrand A, Kalyango J, Alfvén T, Darenberg J, Kadobera D, Bwanga F, et al
PLoS One 2016 ;11(11):e0166018

Impact of AmpC Derepression on Fitness and Virulence: the Mechanism or the Pathway?
Pérez-Gallego M, Torrens G, Castillo-Vera J, Moya B, Zamorano L, Cabot G, et al
mBio 2016 10;7(5):

Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation.
Sharma-Chawla N, Sender V, Kershaw O, Gruber AD, Volckmar J, Henriques-Normark B, et al
Infect Immun 2016 Dec;84(12):3445-3457

Streptococcus pneumoniae Senses a Human-like Sialic Acid Profile via the Response Regulator CiaR.
Hentrich K, Löfling J, Pathak A, Nizet V, Varki A, Henriques-Normark B
Cell Host Microbe 2016 Sep;20(3):307-317

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 08;34(38):4565-4571

Pneumococcal meningitis is promoted by single cocci expressing pilus adhesin RrgA.
Iovino F, Hammarlöf DL, Garriss G, Brovall S, Nannapaneni P, Henriques-Normark B
J Clin Invest 2016 08;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 09;101(6):954-67

lytA-based identification methods can misidentify Streptococcus pneumoniae.
Simões AS, Tavares DA, 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 Mar;7(2):e00168-16

How Does Streptococcus pneumoniae Invade the Brain?
Iovino F, Seinen J, Henriques-Normark B, van Dijl JM
Trends Microbiol 2016 Apr;24(4):307-315

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 MS, Escudero L, Sylvius N, Norman M, Henriques-Normark B, Andrew PW
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 AA, Holzmann B, Henriques-Normark B, et al
Mucosal Immunol 2016 09;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 VP, 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 SM, 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 LS, Dennison SH, 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 SB, Olsen RJ, Dean MA, Rice KA, Long SW, 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 CG, et al
BMC Infect Dis 2014 Dec;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 OP
Microbiology (Reading) 2015 Jan;161(Pt 1):41-49

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 JG, Quinten C, Hruba F, Busana MC, Lopalco PL, 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 DM, Guglielmini J, McMillan DJ, Vu T, Holien JK, 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 Feb;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 Jan;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 MR, 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 TH, Wang CY, 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 NJ, Mitchell AM, Gould KA, 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)