Dissecting the stealthy gut colonization of the human pathogen Klebsiella pneumoniae.

Your gut houses a bustling community of trillions of microbes, mostly bacteria, containing more genes than the human genome. These microbes are involved in functions crucial to your health. These bacteria help to digest the food you eat, and they help with absorbing and synthesizing nutrients too. Gut microbes are involved in many other important processes including your body weight, your defense against infections, as well as your brain functions and they may even alleviate your anxiety. Not surprisingly, there is intensive research to find ways to improve our health by controlling and manipulating the resident microbes of the gut. Unfortunately, recent research has shown that our gut may also house other microbes, hidden, that cause infections when disseminate from the gut to other tissues. In fact, a number of studies interrogating patients admitted to the hospital that later develop infections in the blood have clearly established that the patients were the carriers in their guts in an asymptomatic way of the microbe causing the infection. Klebsiella pneumoniae is one of these microbes with the ability to co-exist peacefully in our gut but with also the ability to become a deadly microbe if reaching our tissues such as the lung or the blood. Klebsiella has been singled out as an urgent threat to human health by the UK Government, the U.S. Centers for Disease Control and Prevention, and the World Health Organization due to extremely antibiotic resistant strains. The increasing isolation of strains resistant to "last resort" antibiotics has significantly narrowed, or in some settings completely removed, the therapeutic options. This is particularly alarming in low and middle countries. This research is designed to unveil the incognito lifestyle of Klebsiella in our gut and to establish how Klebsiella can cross the gut to reach other tissues. We will characterize the gut environment promoting Klebsiella colonization and which one is hostile. Particularly, we will identify which of the microbes of our gut are able to out-compete Klebsiella and which ones favour Klebsiella colonization. Lastly, we will define which of the small genetic variations that difference each of us render our gut permissive for Klebsiella colonization, and which ones are restrictive. The findings of this research shall be the foundation of innovative therapeutics to prevent the gut colonization of Klebsiella. These new therapies may involve boosting our gut defenses to generate a harsh environment for Klebsiella, the use of rational design probiotics that include gut microbes efficient eliminating Klebsiella, and antibodies-based treatments or vaccines targeting Klebsiella.