Biofilms and the bacterial subversion of the immune system

I was just talking about how our mucosal surfaces have anti-microbial peptides to keep bacteria at bay. I also mentioned how whatever defenses we have, pathogens find a way to get around them. Case in point:

Our results suggest that curli and cellulose exhibit differential and complementary functions. Both of these biofilm components were expressed by a high proportion of clinical E. coli isolates. Curli promoted adherence to epithelial cells and resistance against the human antimicrobial peptide LL-37, but also increased the induction of the proinflammatory cytokine IL-8. Cellulose production, on the other hand, reduced immune induction and hence delayed bacterial elimination from the kidneys.

Uropathogenic E. coli (UPEC) cause most urinary tract infections, and they form specialized structures called biofilms. As a group of these bacteria divide, they secrete a matrix of proteins and other components that allow them to aggregate and adhere to their environment. And bacteria in biofilms are often behave differently from their free-living counterparts. In fact, it’s been shown that Vibrio cholerae (which causes cholera), is only pathogenic in its bio-film form.

This paper is showing that the biofilm made by uropathogenic E. coli has components called “curli fimbriae” that inhibit the anti-microbial peptide LL-37. They took bacteria samples from patients with UTIs and cultured them, checking for the expression of biofilm components. By far the most infectious strains expressed curli, and if the curli were removed, these trains were no longer infectious. Interestingly, in a classic example of Red Queen evolution (I hope to write more on that later), the immune system has learned to recognize curli fimbriae as signs of infection and mount stronger immune responses. Of course, the bacteria are smarter than we are, and have a counter-counter-measure, cellulose, which prevents the immune system from detecting the curli. Almost all of the strains these guys cultured made cellulose, and when they removed the ability to make cellulose, the UPEC induced a strong immune response and were unable to establish persistant infections.

It would be great to have a way to simply disrupt these biofilms as a treatment for UTIs, since using non-specific antibiotics can have all kinds of other side-effects. This research is probably a long way off, but it’s an important first step.

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