New Insights into E. coli's UTI Survival Strategy

Due to anatomical differences, women are more susceptible to urinary tract infections (UTIs); nearly 50% of women will experience at least one UTI during their lifetime.

For decades, researchers have attempted to understand how bacteria enter otherwise healthy individuals. They have looked at a variety of aspects, including how the bacteria enter the bladder and adhere to its interior as well as how they release toxins that cause unpleasant and frequently excruciating symptoms.

The majority of UTIs are caused by the bacteria Escherichia coli or E. coli. A study that was published in PNAS looks at how E. coli can use host nutrients to multiply incredibly quickly during infection, even in the nearly sterile environment of fresh urine.

To find bacterial genes that might be crucial for establishing infection, researchers in the University of Michigan Medical School's lab of Harry Mobley, Ph.D., started by examining mutant strains that were less successful at replicating in mouse models.

By doing this, they were able to identify a set of genes that regulate transport systems at critical.

When bacteria need something to grow, say an amino acid, they can get it in two ways. They can make it itself, or they can steal it from their host using what we call a transport system.”

Harry Mobley, Frederick G. Novy Distinguished Professor, Department of Microbiology and Immunology, University of Michigan

Their previous gene expression screen revealed that nearly 25% of bacterial genes were dedicated to replication tactics, including transport systems for specific amino acids, which E. coli use to bring in thousands of molecules per second,” said Mobley.

To determine which transport proteins from E. coli were crucial for infection, first author Allyson Shea, Ph.D., an Assistant Professor of Microbiology and Immunology at the University of South Alabama and a former member of Mobley's lab, cross-referenced a library of these proteins against other species of UTI pathogens. Shea found that a particular class of transporters known as ABC (ATP-binding cassette) transporters seemed to be essential.

Then she demonstrated that ABC transporters were necessary for infection using organ agar derived from the mouse urinary tract. Numerous bacterial strains deficient in these nutrient import systems were unable to grow on organ agar containing kidney and bladder tissues.

It appears bacteria make an investment into these energy expensive ATP transport systems in order to have a higher affinity for the energy sources they are interested in. These systems are very, very good at getting nutrients inside the cell.”

Allyson Shea, Ph.D., Assistant Professor and Study First Author, Department of Microbiology and Immunology, University of South Alabama

According to Mobley, the results pave the way for the creation of novel treatments, which is crucial given the current trend of rising antibiotic resistance.

If you inhibit these transport systems, maybe you can inhibit the rapid growth of these bacteria,” Mobley says.

Shea points out that tackling this challenge will not be straightforward, given that bacteria have developed numerous backup systems for this crucial category of transporters.

What’s nice about this ATP-binding family is they all have an ATP binding subunit which gives the transport system the energy it needs to get nutrients across the cell membrane.”

Harry Mobley, Frederick G. Novy Distinguished Professor, Department of Microbiology and Immunology, University of Michigan

The whole transporter family may become dysfunctional if this subunit is targeted.

Shea notes that while this would not necessarily replace antibiotics, it might slow down growth, allowing the host immune system and antibiotics to work together to better stop the bugs.

Source:
Journal reference:

Shea, E., A., et al. (2024) Emerging roles for ABC transporters as virulence factors in uropathogenic Escherichia coli. PNAS. doi.org/10.1073/pnas.2310693121

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