New research has investigated the ability of the bacteria Escherichia coli, also known as E. coli, to rapidly reproduce using host nutrients during urinary tract infections (UTIs), despite the typically sterile environment of fresh urine. This is especially relevant for women, as almost half of them experience a UTI at some point in their lives. Scientists have spent years researching how bacteria are able to infect healthy individuals, examining factors such as their movement and ability to adhere to surfaces inside the body.The research published in the PNAS investigates how the bacteria Escherichia coli, or E. coli, which is responsible for most UTIs, can reproduce rapidly during infection despite the sterile environment of fresh urine. Dr. Harry Mobley and his team at the University of Michigan Medical School started by studying mutant strains that were not as effective at replicating in mouse models to identify bacterial genes that could be crucial for establishing infection. They studied various aspects of the bacteria’s behavior, from its ability to adhere to the bladder to its method of deploying toxins to cause uncomfortable and painful symptoms.The researchers at the University of Michigan discovered a set of genes that are essential in controlling transport systems that allow bacteria to obtain the nutrients they need to grow. According to Dr. Mobley, a professor of Microbiology and Immunology, bacteria can acquire the necessary nutrients for growth in two ways: by producing it themselves, or by stealing it from their host using transport systems. Their previous research showed that about 25% of bacterial genes are involved in replication strategies, such as the transport systems that are used by E. coli to bring in various amino acids.Mobley stated that the bacteria can release hundreds of molecules per second. The first author of the study, Allyson Shea, Ph.D., who used to work in Mobley’s lab and is now an assistant professor of Microbiology and Immunology at the University of South Alabama, compared a library of transport proteins from E. coli with other species of UTI pathogens to identify important proteins for infection. She found that ABC (ATP-binding cassette) transporters were crucial for the process. Using organ agar made from the mouse urinary tract, she confirmed that ABC transporters were indeed essential for infection.Bacterial strains that do not have these nutrient import systems struggled to grow on bladder and kidney organ agar. According to Shea, it seems that bacteria invest in these ATP transport systems in order to have a greater attraction to the energy sources they need. These systems are highly efficient at bringing nutrients into the cell. The discovery of these findings could lead to the creation of new treatments, which is crucial in a time when antibiotic resistance is on the rise. Inhibiting these transport systems may be a way to slow down the rapid growth of these bacteria.”Doing so won’t be easy,” notes Shea, as bacteria have evolved multiple backup systems for this important class of transporters. According to Shea, all members of the ATP-binding family have an ATP binding subunit that provides the energy needed to transport nutrients across the cell membrane. Targeting this subunit could potentially render the entire family of transporters dysfunctional. While this wouldn’t necessarily replace antibiotics, Shea says it could slow down growth, allowing antibiotics and the host immune system to be more effective.Preventing the bugs.
