Health

Next Generation Sequencing: Can It Solve The UTI Puzzle

Urinary tract infections (UTI) are the second most common infection people get in the U.S. They are the reason eight million people see a healthcare provider each year. They are also more common in women.

According to the Office on Women’s Health, UTIs affect women up to 30 times more frequently than males. Furthermore, four out of every ten women who acquire a UTI will get at least one more within six months. It is possible that next generation sequencing (NGS) can play a significant role in diagnosing and treating chronic UTIs.

What Is Next Generation Sequencing?

Next-generation sequencing, or high-throughput sequencing, is the umbrella name for a variety of current sequencing methods. These methods enable significantly faster and cheaper DNA and RNA sequencing than the previously employed Sanger sequencing and have revolutionized the study of genetics and molecular biology.

DNA sequencing is revolutionizing our understanding of genetics and disease. It utilizes a process that is similar to natural DNA replication. When a cell repeats its DNA, it uses a polymerase, which is a specialized enzyme.

The cell starts by unraveling its DNA into two separate single strands. The polymerase then binds to a single strand of DNA and fills up the gaps one nucleotide at a time. The nucleotides (A, T, G, or C) then fill up the gaps in the single-stranded DNA to make a full piece of double-stranded DNA. As a result, creating a duplicate.

NGS follows this same process but can sequence millions of fragments simultaneously. Other forms of sequencing, like Sanger, work on one strand at a time.

NGS and UTIs

NGS is a tool able to provide a comprehensive evaluation of the urinary microbiome. This is important for someone with chronic UTIs and bladder diseases such as chronic interstitial cystitis.

Current Diagnostics Tools

Urine culture is the gold-standard diagnostic method for UTIs. In other words, the diagnosis depends on the capacity of the same microorganisms causing the infection to grow under artificial circumstances. The issue with a culture is that many organisms that cause symptomatic urinary tract infections do not grow on normal culture media or develop as “mixed urogenital flora,” making identifying a causal pathogen difficult or impossible.

How NGS Can Provide Advanced Microbial Analysis

There are two options for advanced microbial analysis: NGS or polymerase chain reaction or PCR. PCR includes amplifying DNA and matching that DNA to a small number of known species.

If the patient has one of the 40 or fewer species in the test panel, PCR testing has a significantly greater probability of producing a positive result than culture. PCR on its own, however, is not conclusive because of its limitations. Next generation sequencing (NGS) examines all microbial DNA inside a sample instead of the 40 species detected by PCR.

A PCR test will tell you that the infection does not involve one of 40 microorganisms. NGS expands that reach to include all potentially invading organisms.

The downside to NGS is cost. The fact is a PCR test will catch the most common pathogens. It may only be necessary to have that extra expense in some cases. A more affordable NGS may become the standard diagnostic tool for UTIs as the technology improves, though.

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