Chronic infection is, in a way, the new emerging infectious disease. Many pathogens are relatively tenacious when they infect elderly individuals or individuals who are otherwise not fully immunocompetent, and such individuals are, thanks to modern medical technology and practice, more common in the population. Resistant bacteria can cause chronic infection. It is interesting to see more research oriented specifically towards the problem of chronic infection as a problem in and of itself, and a paper just out by Hannan, Mysorekar, Hung, Isaacson-Schmit and Hultgren, in PLoS Pathogens, is an interesting and important example of one such research project.
The paper is Early Severe Inflammatory Responses to Uropathogenic E. coli Predispose to Chronic and Recurrent Urinary Tract Infection, and, since PLoS is an OpenAccess journal, it is available here.
Urinary tract infections in human females are often chronic, recurring as painful inflammations as well as the regular production of the offending strain of E. coli even between bouts of inflammation. Other times the infections are readily dealt with using antibiotics. Why the difference? The research reported here sought explanations other than infection by resistant strains of bacteria (which is certainly an issue as well). Essentially, the experimenters infected mice that were essentially the same in most but not all respects with the same E. coli, but at varying levels. Some of the mice ended up with chronic infections, and some did not.
Some of the mice possessed normal amounts of run of the mill TLR4 signaling molecules. In other words, the capacity for the immune system of the mice to recognize an infection and start the process of developing a response was intact. Other mice had immune systems that were deficient in this area or otherwise unable to respond vigorously to the infection.
Counter-intuitively, the mice with the very excellent immune systems responded to the infection in such a way that the tissues of their bladders were damaged. This damage facilitated a chronic infection. Those mice with sub-par immune systems did not have this problem and, on average, did not develop chronic infections. (This also depended on the dose of the infection, and I’m oversimplifying a great deal.)
In addition, once a mouse did develop a severe infection, the chance of subsequent chronic infection was greater.
In summary, we have discovered a new basis for understanding UTI [Urinary tract infection] that provides a possible mechanism for both chronic and recurrent infection. We propose that, in females that are genetically predisposed to enhanced mucosal TLR4 signaling, initial episodes of UTI … may be particularly severe … If allowed to progress past the early acute stage before initiation of antibiotic therapy, these individuals could then develop altered bladder mucosal responses to gram-negative uropathogens. Upon repeated exposure to gram-negative uro- pathogens, these individuals would then be at increased risk for developing severe, symptomatic rUTI.
In addition, the scientists looked at physical reservoirs for (small numbers of) pathogenic bacteria that may be the seed for repeated infections in mice, and speculated that such a reservoir may be present in humans.
How will this affect future research and treatment options? As you know, much research is not about solving specific ‘end user’ problems, but rather, about knowing more stuff about stuff. But this research seems closer to practical application than a lot of other research. It would seem that reducing specific immune responses (in a limited way) could be part of treatment. Also, having a genetic factor at the table can help to design better drugs that may assist the antibiotics. There is nothing in this research that should guide actual human females dealing with actual urinary tract infections. But there is progress being made.
Intelligent design indeed.
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Hanan, T.H., Mysorekar, I.U., Hung, C.S., Isaacson-Schmid, J.L., & Hultgren, S.J. (2010). Early Severe Inflammatory Responses to Uropathogenic E. coli Predispose to Chronic and Recurrent Urinary Tract Infection
PLoS Pathogens, 6 (8) : 10.1371/journal.ppat.1001042