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
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.
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
Publications - Birgitta Henriques-Normark
Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study.
Lancet Respir Med 2017 Aug;5(8):648-656
Analysis of IAV Replication and Co-infection Dynamics by a Versatile RNA Viral Genome Labeling Method.
Cell Rep 2017 Jul;20(1):251-263
Structure of the competence pilus major pilin ComGC in Streptococcus pneumoniae.
J. Biol. Chem. 2017 Jun;():
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.
ACS Nano 2017 Apr;11(4):3438-3445
The Pneumocell-study: Vaccination of IgG1- and IgG2-deficient patients with Prevnar13.
Vaccine 2017 May;35(20):2654-2660
Vitamin D Promotes Pneumococcal Killing and Modulates Inflammatory Responses in Primary Human Neutrophils.
J Innate Immun 2017 ;9(4):375-386
Coeliac disease and invasive pneumococcal disease: a population-based cohort study.
Epidemiol. Infect. 2017 Apr;145(6):1203-1209
N-acetylglucosamine-Mediated Expression of nagA and nagB in Streptococcus pneumoniae.
Front Cell Infect Microbiol 2016 ;6():158
Pneumococcal Carriage in Children under Five Years in Uganda-Will Present Pneumococcal Conjugate Vaccines Be Appropriate?
PLoS ONE 2016 ;11(11):e0166018
Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation.
Infect. Immun. 2016 Dec;84(12):3445-3457
Streptococcus pneumoniae Senses a Human-like Sialic Acid Profile via the Response Regulator CiaR.
Cell Host Microbe 2016 Sep;20(3):307-317
Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity.
PLoS ONE 2016 ;11(8):e0160734
Pneumococcal meningitis is promoted by single cocci expressing pilus adhesin RrgA.
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.
Mol. Microbiol. 2016 Sep;101(6):954-67
lytA-based identification methods can misidentify Streptococcus pneumoniae.
Diagn. Microbiol. Infect. Dis. 2016 Jun;85(2):141-8
How Does Streptococcus pneumoniae Invade the Brain?
Trends Microbiol. 2016 Apr;24(4):307-15
Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm, Sweden.
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.
Infect. Immun. 2016 Apr;84(4):894-905
Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection.
Mucosal Immunol 2016 Sep;9(5):1288-302
Streptococcal M1 Strikes by Neutralizing Cathelicidins.
Cell Host Microbe 2015 Oct;18(4):390-1
Respiratory viruses associated with community-acquired pneumonia in children: matched case-control study.
Thorax 2015 Sep;70(9):847-53
Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types.
Eur. Respir. J. 2014 Dec;44(6):1646-57
Secretion of a pneumococcal type II secretion system pilus correlates with DNA uptake during transformation.
Proc. Natl. Acad. Sci. U.S.A. 2014 Feb;111(7):E758-65
Sinusitis and pneumonia hospitalization after introduction of pneumococcal conjugate vaccine.
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.
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.
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.
J. Infect. Dis. 2014 Jul;210(1):4-13
Prevalence of community-acquired bacteraemia in Guinea-Bissau: an observational study.
BMC Infect. Dis. 2014 Dec;14():3859
Improvement of CRB-65 as a prognostic tool in adult patients with community-acquired pneumonia.
BMJ Open Respir Res 2014 ;1(1):e000038
UlaR activates expression of the ula operon in Streptococcus pneumoniae in the presence of ascorbic acid.
Microbiology (Reading, Engl.) 2015 Jan;161(Pt 1):41-9
A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development.
J. Infect. Dis. 2014 Oct;210(8):1325-38
Structural and functional insights into peptidoglycan access for the lytic amidase LytA of Streptococcus pneumoniae.
MBio 2014 Feb;5(1):e01120-13
Clinical utility of PCR for common viruses in acute respiratory illness.
Pediatrics 2014 Mar;133(3):e538-45
Focal targeting by human β-defensin 2 disrupts localized virulence factor assembly sites in Enterococcus faecalis.
Proc. Natl. Acad. Sci. U.S.A. 2013 Dec;110(50):20230-5
Adult zebrafish model for pneumococcal pathogenesis.
Dev. Comp. Immunol. 2014 Feb;42(2):345-53
Intraclonal variations among Streptococcus pneumoniae isolates influence the likelihood of invasive disease in children.
J. Infect. Dis. 2014 Feb;209(3):377-88
Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae.
J. Infect. Dis. 2013 Nov;208(9):1474-81
|Nils Block||Graduate Student|
|Mario Codemo||PhD student, Graduate Student|
|Hannes Eichner||PhD student, Graduate Student|
|Genevieve Garriss||Assistant professor|
|Birgitta Henriques Normark||Professor/senior physician|
|Jens Karlsson||R&D trainee, Graduate Student|
|Edmund Loh||Assistant professor|
|Peter Mellroth||Senior researcher|
|Sandra Muschiol||Senior lab manager|
|Staffan Normark||Professor, senior|
|Vitor Oliveira||PhD student, Graduate Student|
|Katrin Pütsep||Senior Lecturer, Senior researcher|
|Elisabeth Reithuber||PhD student, Graduate Student|
|Georgios Sotiriou||Assistant professor|
|Anna Syk||Graduate Student, Research engineer|