Annelie Brauner Project
The host – microbe interaction is of prime importance to understand why some people get recurrent or complicated infections, while others do not. Our primary focus is infections in the urinary tract, and the skin. We specifically investigate the early defence mechanisms which protect the body from invading bacteria, and how we can exploit these natural strategies for possible therapeutic purposes.
Innate immunity during UTI and skin infection
Why are some patients more susceptible to infections?
Urinary tract infections (UTIs) belong to the most common bacterial infections worldwide and are primarily caused by uropathogenic Escherichia coli. To infect and remain in the urinary tract, E. coli are equipped with a variety of virulence factors, which allow colonisation of the tissue and evade the innate immune defence mechanisms of the host. We investigate this struggle of host and pathogen from both sides. As our research focuses on clinical issues, most of our studies are based on clinical material. Using established cell culture systems, molecular techniques, and mouse models in combination with clinical samples, we can reveal why some patient groups are more susceptible to UTIs.
Repurposing common drugs to increase the innate immune response
Infections, including UTIs, are common in patients with diabetes. However, treatment with antibiotics is becoming a major problem due to increasing resistance. In this line, we are continuing to focus on how diabetes affects the production of antimicrobial peptides and innate immunity. In addition to analysing the effect of diabetes on host defence, we investigate how repurposing of certain drugs, such as hypoxia-inducible factor 1 activators, and the antidiabetic drug metformin, can strengthen uroepithelial immunity by stimulating resident uroepithelial cells to produce the antimicrobial peptides LL-37 and RNase 7, in addition to triggering expression of pro-inflammatory cytokines.
Novel gels an alternative to treat skin infections
Skin infections are common amongst all age groups, but are more prevalent and dangerous amongst patients with long term systemic disease. Recently, we showed that a novel cationic hydrogel based on amino-functional hyperbranched dendritic-linear-dendritic copolymers exhibit striking antimicrobial activity towards clinical skin pathogens (including drug-resistant strains). In addition to the direct antibacterial activity, we observed that the hydrogels could induce the expression of important antimicrobial peptides in human skin, including RNase 7 and psoriasin. This dual-sided activity of the compound are promising for designing compounds, such as nanomaterials or novel synthetic AMPs, for combating infection and strengthening innate defence mechanisms, which is one of the research lines that we follow now.
HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients.
Mohanty S, Kamolvit W, Zambrana S, Gonzales E, Tovi J, Brismar K, Östenson CG, Brauner A
J Mol Med (Berl) 2021 Oct;():
Dendritic Hydrogels Induce Immune Modulation in Human Keratinocytes and Effectively Eradicate Bacterial Pathogens.
Fan Y*, Mohanty S*, Zhang Y, Lüchow M, Qin L, Fortuin L, Brauner A#, Malkoch M#
J Am Chem Soc 2021 Oct;143(41):17180-17190
* Shared first authors
# Shared last and corresponding authors
Metformin strengthens uroepithelial immunity against E. coli infection.
Majhi RK, Mohanty S, Kamolvit W, White JK, Scheffschick A, Brauner H, Brauner A
Sci Rep 2021 09;11(1):19263
Ag@ZnO Nanoparticles Induce Antimicrobial Peptides and Promote Migration and Antibacterial Activity of Keratinocytes.
Majhi RK, Mohanty S, Khan MI, Mishra A, Brauner A
ACS Infect Dis 2021 08;7(8):2068-2072
Vitamin D strengthens the bladder epithelial barrier by inducing tight junction proteins during E. coli urinary tract infection.
Mohanty S, Kamolvit W, Hertting O, Brauner A
Cell Tissue Res 2020 Jun;380(3):669-673
Statins influence epithelial expression of the anti-microbial peptide LL-37/hCAP-18 independently of the mevalonate pathway.
Lüthje P, Walker S, Kamolvit W, Mohanty S, Pütsep K, Brauner A
Clin Exp Immunol 2019 02;195(2):265-276
Antibiotic Overconsumption in Pregnant Women With Urinary Tract Symptoms in Uganda.
Sekikubo M, Hedman K, Mirembe F, Brauner A
Clin Infect Dis 2017 Aug;65(4):544-550
The impact of vitamin D on the innate immune response to uropathogenic Escherichia coli during pregnancy.
Ramos NL, Sekikubo M, Kironde F, Mirembe F, Sääf M, Brauner A
Clin Microbiol Infect 2015 May;21(5):482.e1-7
Estrogen supports urothelial defense mechanisms.
Lüthje P, Brauner H, Ramos NL, Ovregaard A, Gläser R, Hirschberg AL, Aspenström P, Brauner A
Sci Transl Med 2013 Jun;5(190):190ra80
The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection.
Chromek M, Slamová Z, Bergman P, Kovács L, Podracká L, Ehrén I, Hökfelt T, Gudmundsson GH, Gallo RL, Agerberth B, Brauner A
Nat Med 2006 Jun;12(6):636-41
- Annelie Brauner, professor and research group leader
- Soumitra Mohanty post doc
- Rakesh Kumar Majhi, Ph.D
- Witchuda Kamolvit, M.D, Ph.D.
- Musa Sekikubo, M.D, Ph.D.
- Cathrin Alvendal, M.D, Ph.D.
- Petra Lüthje, DVMS, Ph.D
- Nubia Ramos, Ph,D
- Milan Chromek, M.D., Ph.D.
- Olof Hertting, M.D., Ph.D.