Annelie Brauner Group

Innate immunity and E. coli in the urinary tract

We investigate the interaction between the patient and bacteria in the urinary tract. We specially focus on early defense mechanisms which protect the body from invading bacteria; and how we can use these natural strategies for therapeutic purposes.

Urinary tract infections (UTI) belong to the most common infections worldwide and are primarily caused by E. coli. To be able to infect the urinary tract, uropathogenic E. coli are equipped with a number of virulence factors, which allow the colonization of the tissue despite the defense mechanisms of the host. We are investigating this battle between host and pathogen, considering both aspects of the host and E. coli. Since we address clinical questions, most of our studies are based on clinical material; we apply cell culture systems and use molecular techniques to reveal underlying mechanisms.

We have analyzed extracellular matrix components involved in bacterial biofilm formation for their interaction with the host. Surprisingly, bacterial biofilm factors provide opposing effects in the pathogenesis of infection; while curli fimbrie promote adhesion and invasion of host cells, they also cause a stronger immune response. Other factors such as cellulose do protect the bacterium from immune recognition, but at the same time reduce the infectiveness of the strain. We have also discovered that adhesive curli fimbriae on one hand protect from, but at the same time are a target for the antimicrobial peptide LL-37, which plays an important role in the defense against UTI.

The instant response to bacterial infection is located at the epithelial cells lining the urinary tract, as these cells are the first in contact with the bacteria. This defense barrier is influenced by hormones such as vitamin D and estrogen. We have shown that exogenous supplementation with these hormones promote the antimicrobial properties of the urothelium, thus providing a prophylactic potential against UTI. Correspondingly, bacterial populations originating from patient groups with different hormonal background, i.e. pregnant or postmenopausal women, carry distinct repertoires of virulence factors.

The vagina is considered one major reservoir of E. coli infecting the urinary tract. Therefore, a disturbed vaginal microflora may have an impact on the susceptibility of the patient to UTI. Apart from bacteria, fungi such as Candida contribute to this microbial community. While Candida belongs to the commensal flora of the vaginal mucosa, it can also cause infections known as vaginal candidiasis. For reasons not well understood, these infections tend to recur in young, otherwise healthy women. Based on a unique collection of clinical material, we are investigating the mechanisms which may be responsible for this severe disease condition. In the light of increased antimicrobial resistance against conventional antibiotics, novel approaches to prevent and treat infections are highly needed. In ongoing studies we aim to further elucidate the above mentioned and additional endogenous defense mechanisms to develop alternative prevention and treatment strategies for potential clinical use.



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

Alterations of c-di-GMP turnover proteins modulate semi-constitutive rdar biofilm formation in commensal and uropathogenic Escherichia coli.
Cimdins A, Simm R, Li F, Lüthje P, Thorell K, Sjöling , et al
Microbiologyopen 2017 Oct;6(5):

Vitamin D-deficient mice have more invasive urinary tract infection.
Hertting O, Lüthje P, Sullivan D, Aspenström P, Brauner A
PLoS ONE 2017 ;12(7):e0180810

Stand-Alone EAL Domain Proteins Form a Distinct Subclass of EAL Proteins Involved in Regulation of Cell Motility and Biofilm Formation in Enterobacteria.
El Mouali Y, Kim H, Ahmad I, Brauner A, Liu Y, Skurnik M, et al
J. Bacteriol. 2017 Sep;199(18):

"It's a gut feeling" - Escherichia coli biofilm formation in the gastrointestinal tract environment.
Rossi E, Cimdins A, Lüthje P, Brauner A, Sjöling , Landini P, et al
Crit. Rev. Microbiol. 2018 Feb;44(1):1-30

Elevated nitric oxide in recurrent vulvovaginal candidiasis - association with clinical findings.
Alvendal C, Ehrström S, Brauner A, Lundberg J, Bohm-Starke N
Acta Obstet Gynecol Scand 2017 Mar;96(3):295-301

Extract of Clinopodium bolivianum protects against E. coli invasion of uroepithelial cells.
Mohanty S, Kamolvit W, Zambrana S, Sandström C, Gonzales E, Östenson C, et al
J Ethnopharmacol 2017 Feb;198():214-220

Draft Genome Sequences of Semiconstitutive Red, Dry, and Rough Biofilm-Forming Commensal and Uropathogenic Escherichia coli Isolates.
Cimdins A, Lüthje P, Li F, Ahmad I, Brauner A, Römling U
Genome Announc 2017 Jan;5(4):

Elevated nitric oxide in recurrent vulvovaginal candidiasis - association with clinical findings.
Alvendal C, Ehrström S, Brauner A, Lundberg J, Bohm-Starke N
Acta Obstet Gynecol Scand 2017 Mar;96(3):295-301

A ten-year retrospective case series of glucocorticoid treatment of bacterial meningitis in children.
Ygberg S, Brauner A, Chambers B, Wiklund C, Nilsson A
Acta Paediatr. 2016 Aug;105(8):979-82

Retuning of Mouse NK Cells after Interference with MHC Class I Sensing Adjusts Self-Tolerance but Preserves Anticancer Response.
Wagner A, Wickström S, Tallerico R, Salam S, Lakshmikanth T, Brauner H, et al
Cancer Immunol Res 2016 Feb;4(2):113-23

Depletion of IL-2 receptor β-positive cells protects from diabetes in non-obese diabetic mice.
Brauner H, Hall H, Flodström-Tullberg M, Kärre K, Höglund P, Johansson S
Immunol. Cell Biol. 2016 Feb;94(2):177-84

Improved cell surface display of Salmonella enterica serovar Enteritidis antigens in Escherichia coli.
Gustavsson M, Do T, Lüthje P, Tran N, Brauner A, Samuelson P, et al
Microb. Cell Fact. 2015 Apr;14():47

Bacterial nanoscale cultures for phenotypic multiplexed antibiotic susceptibility testing.
Weibull E, Antypas H, Kjäll P, Brauner A, Andersson-Svahn H, Richter-Dahlfors A
J. Clin. Microbiol. 2014 Sep;52(9):3310-7

Markers of innate immune activity in patients with type 1 and type 2 diabetes mellitus and the effect of the anti-oxidant coenzyme Q10 on inflammatory activity.
Brauner H, Lüthje P, Grünler J, Ekberg N, Dallner G, Brismar K, et al
Clin. Exp. Immunol. 2014 Aug;177(2):478-82

Estrogenic action on innate defense mechanisms in the urinary tract.
Lüthje P, Hirschberg A, Brauner A
Maturitas 2014 Jan;77(1):32-6

Decoctions from Citrus reticulata Blanco seeds protect the uroepithelium against Escherichia coli invasion.
Vollmerhausen T, Ramos N, Dzung D, Brauner A
J Ethnopharmacol 2013 Nov;150(2):770-4

Red meat allergy in Sweden: association with tick sensitization and B-negative blood groups.
Hamsten C, Tran T, Starkhammar M, Brauner A, Commins S, Platts-Mills T, et al
J. Allergy Clin. Immunol. 2013 Dec;132(6):1431-1434

Estrogen supports urothelial defense mechanisms.
Lüthje P, Brauner H, Ramos N, Ovregaard A, Gläser R, Hirschberg A, et al
Sci Transl Med 2013 Jun;5(190):190ra80

Clean intermittent catheterization and urinary tract infection: review and guide for future research.
Wyndaele J, Brauner A, Geerlings S, Bela K, Peter T, Bjerklund-Johanson T
BJU Int. 2012 Dec;110(11 Pt C):E910-7

Uropathogenic Escherichia coli isolates from pregnant women in different countries.
Ramos N, Sekikubo M, Dzung D, Kosnopfel C, Kironde F, Mirembe F, et al
J. Clin. Microbiol. 2012 Nov;50(11):3569-74

Septicaemia caused by Arcanobacterium haemolyticum smooth type in an immunocompetent patient.
Hedman K, Brauner A
J. Med. Microbiol. 2012 Sep;61(Pt 9):1328-9

Do Escherichia coli strains causing acute cystitis have a distinct virulence repertoire?
Norinder B, Köves B, Yadav M, Brauner A, Svanborg C
Microb. Pathog. 2012 Jan;52(1):10-6

Cellulose and PapG are important for Escherichia coli causing recurrent urinary tract infection in women.
Norinder B, Lüthje P, Yadav M, Kadas L, Fang H, Nord C, et al
Infection 2011 Dec;39(6):571-4

Labisia pumila var. alata reduces bacterial load by inducing uroepithelial cell apoptosis.
Fazliana M, Ramos N, Lüthje P, Sekikubo M, Holm A, Wan Nazaimoon W, et al
J Ethnopharmacol 2011 Jun;136(1):111-6

Characterisation of uropathogenic Escherichia coli from children with urinary tract infection in different countries.
Ramos N, Dzung D, Stopsack K, Jankó V, Pourshafie M, Katouli M, et al
Eur. J. Clin. Microbiol. Infect. Dis. 2011 Dec;30(12):1587-93

Lactuca indica extract interferes with uroepithelial infection by Escherichia coli.
Lüthje P, Dzung D, Brauner A
J Ethnopharmacol 2011 Jun;135(3):672-7

The erythropoietin analogue ARA290 modulates the innate immune response and reduces Escherichia coli invasion into urothelial cells.
Polgárová K, Lüthje P, Cerami A, Brauner A
FEMS Immunol. Med. Microbiol. 2011 Jul;62(2):190-6

Vitamin D induction of the human antimicrobial Peptide cathelicidin in the urinary bladder.
Hertting O, Holm , Lüthje P, Brauner H, Dyrdak R, Jonasson A, et al
PLoS ONE 2010 Dec;5(12):e15580

Virulence characteristics of translocating Escherichia coli and the interleukin-8 response to infection.
Ramos N, Lamprokostopoulou A, Chapman T, Chin J, Römling U, Brauner A, et al
Microb. Pathog. 2011 Feb;50(2):81-6

Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37.
Kai-Larsen Y, Lüthje P, Chromek M, Peters V, Wang X, Holm A, et al
PLoS Pathog. 2010 Jul;6(7):e1001010

Is there a risk of cancer development after Campylobacter infection?
Brauner A, Brandt L, Frisan T, Thelestam M, Ekbom A
Scand. J. Gastroenterol. 2010 Aug;45(7-8):893-7

Low immunogenicity allows Staphylococcus epidermidis to cause PD peritonitis.
Jung K, Lüthje P, Lundahl J, Brauner A
Perit Dial Int ;31(6):672-8

Ag43 promotes persistence of uropathogenic Escherichia coli isolates in the urinary tract.
Lüthje P, Brauner A
J. Clin. Microbiol. 2010 Jun;48(6):2316-7

Stereotyping at the undergraduate level revealed during interprofessional learning between future doctors and biomedical scientists.
Lewitt M, Ehrenborg E, Scheja M, Brauner A
J Interprof Care 2010 Jan;24(1):53-62

Genetic relatedness and virulence gene profiles of Escherichia coli strains isolated from septicaemic and uroseptic patients.
Ramos N, Saayman M, Chapman T, Tucker J, Smith H, Faoagali J, et al
Eur. J. Clin. Microbiol. Infect. Dis. 2010 Jan;29(1):15-23

Characteristics of biofilms from urinary tract catheters and presence of biofilm-related components in Escherichia coli.
Wang X, Lünsdorf H, Ehrén I, Brauner A, Römling U
Curr. Microbiol. 2010 Jun;60(6):446-53

Putative link between the virulence-associated fluA gene and fluoroquinolone resistance in uropathogenic Escherichia coli.
Lüthje P, Brauner A
J. Clin. Microbiol. 2010 Feb;48(2):675-6

Host species-specific translocation of Escherichia coli.
Katouli M, Ramos N, Nettelbladt C, Ljungdahl M, Robinson W, Ison H, et al
Eur. J. Clin. Microbiol. Infect. Dis. 2009 Sep;28(9):1095-103

Characterization of cellulose production in Escherichia coli Nissle 1917 and its biological consequences.
Monteiro C, Saxena I, Wang X, Kader A, Bokranz W, Simm R, et al
Environ. Microbiol. 2009 May;11(5):1105-16

Antimicrobial mechanisms of the urinary tract.
Chromek M, Brauner A
J. Mol. Med. 2008 Jan;86(1):37-47

Cytotoxic necrotizing factor 1 (CNF1) induces an inflammatory response in the urinary tract in vitro but not in vivo.
Hertting O, Chromek M, Slamová Z, Kádas L, Söderkvist M, Vainumäe I, et al
Toxicon 2008 Jun;51(8):1544-7

The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection.
Chromek M, Slamová Z, Bergman P, Kovács L, Podracká L, Ehrén I, et al
Nat. Med. 2006 Jun;12(6):636-41

Interleukin-8 response in cells from the human urinary tract induced by lipopolysaccharides of Proteus mirabilis O3 and O18.
Chromek M, Stankowska D, Dadfar E, Kaca W, Rabbani H, Brauner A
J. Urol. 2005 Apr;173(4):1381-4

Interleukin-8 response in cells from the human urinary tract induced by lipopolysaccharides of Proteus mirabilis O3 and O18.
Chromek M, Stankowska D, Dadfar E, Kaca W, Rabbani H, Brauner A
J. Urol. 2005 Apr;173(4):1381-4

Group Members

Professor, senior

Annelie Brauner

Organizational unit: Department of Microbiology, Tumor and Cell Biology (MTC), C1

Annelie BraunerAdjunct professor
Witchuda KamolvitPostdoc
Soumitra MohantyAssociated
Musa SekikuboGraduate Student

Former Members

  Milan Chromek currently a practicing pediatrician at Huddinge

    PhD Olof Herting