Jan. 3, 2008 A new study presents convincing evidence that intracellular bacterial communities (IBCs) commonly exist in women with bladder infections and may contribute to the recurrence of these infections. In mice it has already been established that Escherichia coli (E coli), a type of bacterium that causes urinary tract infections, can avoid the immune system by invading cells lining the bladder, replicate and ultimately re-infect the urinary tract. The existence of IBCs in this new study suggests that a similar cycle may occur in people and that perhaps longer treatment with antibiotics that kill bacteria inside human cells may be necessary for some patients.
Every year, nearly ten million people in the United States -- mainly women -- consult their doctors because of urinary tract infections, which commonly include cystitis (inflammation of the bladder). To investigate whether IBCs are present in these infections, David Rosen and colleagues at Washington University in St Louis and the University of Washington in Seattle collected urine samples from eighty women with cystitis and from twenty women who a history of cystitis but no longer had any symptoms of it.
Using light microscopy, electron microscopy and a technique called immunofluorescence (the identification of antibodies and antigens with fluorescent dyes), the researchers found IBCs in the urine samples of nearly one in five of the women with cystitis. Nearly half of the women with cystitis -- including all of those who had IBCs -- had filamentous bacteria in their urine. These are bacteria assuming a long, slender shape as part of a mechanism to spread in the urinary tract. Moreover, most of the women with filamentous bacteria -- and all of the women with IBCs -- had infections caused by E coli: the bacteria species that has been shown to persist in and cause the re-infection of the bladders of mice. None of the women without cystitis had IBCs or filamentous bacteria.
The samples were only taken at one point in time, so further studies will be needed to translate these findings into clinical applications. The findings suggest that the IBC cycle occurs in humans and that it is associated with infections caused by E coli. Indeed, as only one sample was collected from each woman, IBCs may be even more common than indicated in the study.
In a related article* Steven Opal reviews the phenomenon of bacteria communicating with each other and coordinating their activities, rather than acting as solitary microorganisms ("lone soldiers"). Such communication was initially observed in a bioluminescent bacterium known as Vibrio fischeri, which forms an unusual symbiotic relationship with the Hawaiian bobtail squid. The bacterium is taken up by light organs along the body of the squid and, when high concentrations of bacteria are attained, the bacterium induces its genes known as luciferase genes to generate visible light.
The bacteria benefit from this relationship, as the squid provides a source of nutrients. The squid benefits from the microbial light source, since it provides a unique form of camouflage for the squid during night time mating rituals. Communication between the bacteria occurs through their production of a soluble “quorum sensing" molecule. Dr Opal links this phenomenon to the bacterial communities in urinary tract infections in women, as described by Rosen and colleagues. He states that Rosen and colleagues' study raises the possibility that detection of intracellular bacterial communities in people "might help identify patients who may benefit from a longer course of antimicrobial agents, or from agents that penetrate the intracellular space."
Citation: Rosen DA, Hooton TM, Stamm WE, Humphrey PA, Hultgren SJ (2007) Detection of intracellular bacterial communities in human urinary tract infection. PLoS Med 4(12): e329. http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040329
*Related PLoS Medicine Research in Translation Article: Opal SM (2007) Communal living by bacteria and the pathogenesis of urinary tract infections. PLoS Med 4(12): e349.
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