The Birgitta Henriques-Normark Laboratory

Our research

Our main research areas are within infection biology, respiratory tract and invasive infections, host-bacterial interactions, pathogenesis, infection epidemiology, antimicrobial resistance, new antimicrobials, vaccines, and nanoparticle science. The projects range from basic microbiology and bacterial regulatory systems, and immune response of the host, to epidemiological and clinical studies.

The innate immune defense and bacterial infections

The interaction between the innate immune system and microbial pathogens including for example different immune cells (macrophages, dendritic cells, neutrophils, and T cells), Toll like receptors, NODs, scavenger receptors and antimicrobial peptides are being studied.

Edmund Loh publication in Journal of Bacteriology May 2015 in depth

Pathogenic Neisseria express type four pili (Tfp) which are important for adhesion, aggregation and transformation. Some strains of N. meningitidis are able to vary the sequence of the major subunit (PilE) of the Tfp. The mechanisms underlying this variation are not fully defined but the process requires several non-coding elements that are found adjacent to the pilE gene. In this work, Edmund and colleagues have identified a cis-encoded RNA antisense to pilE in N. meningitidis. Using Northern blot and RT-PCR analysis, they have found that the RNA is expressed in stationary phase or following salt stress. This work also indicates that this RNA does not significantly affect pilE or pilin expression levels but instead appears to modulate pilin variation.

Edmund Loh article in Nature Research Microbiology Community, published June 26, 2020.

Edmund Loh article in SCELSE, published 25 May, 2020.

Selected Publications

RNA Thermometers in Bacterial Pathogens.
Loh E, Righetti F, Eichner H, Twittenhoff C, Narberhaus F
Microbiol Spectr 2018 04;6(2):

Thermoregulation of Meningococcal fHbp, an Important Virulence Factor and Vaccine Antigen, Is Mediated by Anti-ribosomal Binding Site Sequences in the Open Reading Frame.
Loh E, Lavender H, Tan F, Tracy A, Tang CM
PLoS Pathog. 2016 08;12(8):e1005794

Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis.
Barnwal RP, Loh E, Godin KS, Yip J, Lavender H, Tang CM, et al
Nucleic Acids Res. 2016 Nov;44(19):9426-9437

Characterization of a novel antisense RNA in the major pilin locus of Neisseria meningitidis influencing antigenic variation.
Tan FY, Wörmann ME, Loh E, Tang CM, Exley RM
J. Bacteriol. 2015 May;197(10):1757-68

Contact

Our mission is to develop materials, devices, tools and methods for medicine using engineering sciences. Our key focus is on flame aerosol engineering of smart nanoscale materials and devices investigating the parameters that influence their performance in theranostics. Our approach is highly multidisciplinary combining expertise from material engineering, bioengineering and health sciences. This allows for the design of bionanomaterials that exhibit the desired functionality in applications ranging from biosensing to therapeutic interventions.

Visit Georgios Sotiriou Laboratory

Salmonella enterica as a model for intracellular parasitism- the research of Mikael Rhen group.

Salmonella enterica as a model for intracellular parasitism

The bacterial species Salmonella enterica includes more than 2000 so-called serovars, many of which infect man and animals, possibly even plants. In man, S. enterica mainly causes two types of diseases; a rather common variant in the form of an inflammatory gastroenteritis, and a severe form termed typhoid or paratyphoid fever affecting annually no less than 20 million individuals. On top of this burden, S. enterica is increasingly becoming resistant to antibiotics.

S. enterica is a bacterium closely related to Escherichia coli and easily accessible in terms of biochemical and genetic probing. A very hallmark of salmonellosis is the tight interplay between the pathogen and host cells. Thus, S. enterica has served as a classical model organism not only for dissecting basic cellular biochemical and genetic principles, but also for dissecting aspects of bacterial intracellular parasitism. This prospect of combining basic biochemistry and bacterial genetics with microbial pathogenesis provides the basis of our very research interests.

We have previously demonstrated that S. enterica experience dramatic differential in environment as it transits form an external milieu into the intravacuolar compartment of mammalian cells. In part, this environmental shift is primed by innate host defence measures, such as the production of reactive oxygen (ROS) and nitrogen species. This had leaded us to probe for the involvement of various oxidoprotective mechanisms in the virulence of the bacteria. Our results indicate that S. enterica possesses several overlapping measures for protection in the form of enzymes degrading ROS and repairing ROS-mediated protein damage. In addition, some of the enzymes involved, such as the thioredoxin 1 and the ScsABCD oxidoreductases, are also engaged in regulating virulence.

Apart from damaging protein and lipids, ROS-species also affect nucleic acids. In E. coli and man RNA damaged by oxidation is degraded by an exoribonuclease termed polybucleotide phosphorylase (PNPase). In S. enterica the gene for PNPase (pnp) is tightly linked to a gene coding for a lipoprotein NlpI and an RNA helicase DeaD. Mutational inactivation of either PNPase or NlpI results in redox-associated phenotypes regarding bacterial virulence. Thus, a further ambition is to probe to what extent RNA degradation in S. enterica is affected by oxidative stress, and to what extent PNPase, NlpI and DeaD contribute to the regulation of virulence gene expression, notably under oxidative stress.

In all, we wish to detail the interplay between bacterial 'house-keeping' functions, such redox management, and the very ability of bacteria to cause disease and colonization. Furthermore, as the antibacterial activities of selected antibiotics are connected to induction of endogenous redox stress, our findings may also aid the development of future regimens for antibacterial treatment.

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