Outsmarting bacteria with fake sugars
Non-antibiotic treatments for bladder infection are on the horizon
Urinary tract infections (UTIs) are among the most frequent bacterial infections in women, accounting for nearly 25% of all infections. Despite effective treatment with antibiotics, almost half of all patients experience recurrent infection.
Recurrent infections are mainly caused by reinfection by the same pathogen. Normally, the urinary tract is considered sterile, but uropathogenic Escherichia coli (UPEC) strain can find shelter in reservoirs in the gut. From there, once they get excreted via the faeces, they can shed off at the perianal region close to the vagina and bladder and ascend upwards.
One out of three women will have to get antibiotic treatment by the age of 24, making UTI a prime example of antibiotic resistance crisis, a public health issue beyond the great discomfort and potential complications for the individual patients.
To add insult to injury, because of general antibiotics overuse, there is a growing prevalence of UPEC infections which are resistant to last-line antibiotic treatments, leaving patients and doctors increasingly helpless.
To change the state of the game, researchers from the Washington University in St. Louis, Missouri together with colleagues from Belgium and Massachusetts published a study in the journal Nature to remedy our dependence on antibiotics to treat UTIs.
They investigated a type of hair-like structure called pilus, consisting of specialized proteins that allow bacteria to bind to surfaces. One of these specialized proteins is called FimH, an adhesin that binds to the sugar mannose which covers the bladder surface, allowing the bacteria to “hook” itself to the bladder and not being washed out during urination.
Imagine UPAC bacteria like climbers on a windy cliff and mannose as the pitons where they anchor their carabiners to. Now anytime the wind blows, even if they lose grip, they will still be anchored on the cliff and don’t fall to death.
Death in that scenario is the equivalent of the bacteria being washed out by urination, the bodies natural reaction to a bladder infection. That is why we have to pee so often. Our body does not want these bacteria on that cliff (our bladder), and it certainly does not want them to reach the peak and cause a kidney infection. Sometimes the body wins on his own, but sometimes those damn bacteria are just too well equipped and have millions climbers waiting for their chance.
In the latter scenario, Spaulding C. et al. came up with a novel strategy to turn the odds to our bodies favor again. After establishing how important FimH binding to mannose is in the development of UTIs, and discovering that the same pili-structures also help the bacteria form reservoirs in the gut, they decided to go on offense. Since UPEC binding to mannose is critical for their way up our urinary tract, the researchers wondered if they could fool the bacteria with what is essentially fake-mannose, a chemical compound named M4284 which closely resembles real mannose, optimized to bind even better than original mannose to FimH.
The strategy behind this deception being that if bacteria would bind all the fake-mannose, giving them a false sense of security and grip, they can be easily washed out.
Surprisingly, treatment with M4284 did not only significantly reduce UPEC bacterial numbers in the bladder, but also in the hard-to-tackle reservoirs in the intestine, reducing the probability of recurrent infections. Even if this strategy is unlikely to completely eradicate all UPEC bacteria, it might be sufficient to turn the odds heavily in our bodies favor and prevent infection. In their study with mice, the authors could show that all mice were cured from their UTIs using this novel approach.
In contrast to antibiotics, which are weapons of mass destruction against all bacteria, the good ones and the bad ones, real and fake mannose are just sugars, our body’s microbiota could not care less.
We concluded that M4284 treatment has activity against different UPEC strains in different host genetic backgrounds and gut microbial community contexts.
[…] an increasing number of studies are finding that disruption of the gut microbiota by orally administered antibiotics, especially during childhood, may affect its functional properties in ways that are deleterious to the host […] Therefore, developing therapeutic agents, such as mannosides, that specifically target a pathogen without disrupting the remainder of a microbial community has important ramifications not only for UPEC but also potentially for other infections, including those caused by enteropathogens. -Spaulding C. et al. Nature, 2017
Additionally, more as a little side note, M4284 and real mannose are sugars that cannot even be utilized by our body, meaning that we do not have to worry about calories or gaining weight or even more unpleasant side effects.
We just pee them out, and harmful bacteria with it.
Maybe in the future, more medicines will work like that. Thanks to science, we are closer to that goal than ever before.
Source: Spaulding C. et al. Nature, 2017
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