Annelie Brauner Project
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.
Milan Chromek currently a practicing pediatrician at Huddinge
PhD Olof Herting