Mayo Clinic scientists are building an expansive library of DNA blueprints of disease-causing bacterial species. The unique collection of genomic sequences is serving as a reference database to help doctors provide rapid and precise diagnoses and pinpoint targeted treatments to potentially improve patient outcomes.
The vast data set is also being studied by researchers in an effort to develop new individualized treatments to combat bacteria-related diseases.
Bacterial infections were linked to more than 7 million global deaths in 2019. Of those, nearly 1.3 million were the direct result of drug-resistant bacteria, according to the National Institutes of Health.
"We are developing the Bacterial Whole Genome Sequencing Database because our laboratory regularly encounters unidentifiable bacterial isolates in clinical practice, with the challenge fueled by the evolving antimicrobial resistance crisis," says Robin Patel, M.D., director of Mayo Clinic's Infectious Diseases Research Laboratory. "Not knowing a bacterial sequence creates a dilemma for us when we're trying to determine what's happening with a patient."
The bacterial database, supported in part by the Mayo Clinic Center for Individualized Medicine, contains more than 1,200 DNA sequences of bacterial species recovered from infection sites such as the lungs, urine, joints and blood. Dr. Patel says many of these bacterial species had never been sequenced before.
"Not only had many not been sequenced, but some had not been named," Dr. Patel says.
Dr. Patel and her team are part of a collaborative effort, in association with the Centers for Disease Control and Prevention’s Pathogen Genomics Centers of Excellence, to provide new descriptions of novel bacterial species. The Minnesota Department of Health has joined forces with Mayo Clinic as a key partner in this effort and one of five state health departments participating nationwide.
Scientists have named and described approximately 10,000 bacterial species, but that likely only represents a fraction of the total bacterial diversity. That's because bacteria are found in every habitat on Earth. The minuscule microbes are about a tenth of the diameter of a human hair, with a thick protective outer wall to enable survival in harsh environments, including the human gut and bloodstream. Many bacterial cells are beneficial to the human body, but some cause diseases. All bacteria can divide and multiply exponentially, with mutations occurring throughout the process.
Sequencing bacterial DNA provides a detailed map of the arrangement of the four letters that represent the building blocks of genetic information within the microbe — the As, Cs, Gs and Ts. Dr. Patel says knowing the genomic makeup of each bacterial strain opens the door to a world of discoveries, such as possibly understanding its structure and function and what promotes the emergence of a drug-resistant strain.
"Bacterial genomes can be difficult to sequence and reconstruct because pieces of DNA in bacteria can move around and duplicate each other," Dr. Patel explains. "So, putting it all together is a complicated proposition, especially when you have a novel species where you don't exactly know what it is you're looking for, and you're trying to piece it together."
Leveraging advanced sequencing technologies, Dr. Patel and her team also decode and map bacterial DNA directly from a patient's specimen. This enables precise identification of a patient's unique infecting bacterium and helps guide individualized treatment plans.
Dr. Patel says conventional methods involve days of growing and culturing bacteria in a petri dish and then identifying them. In the meantime, patients may be given one or more antibiotics in hopes of eradicating the harmful bacteria, although their health care team may not know exactly what those bacteria are or whether they are even there.
Dr. Patel says her team is increasingly encountering drug-resistant bacterial species — and not just the so-called "frequent flyers," which include Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and Pseudomonas aeruginosa.
"Bacteria have the ability to mutate on their own or they can acquire resistance genes from other bacteria," Dr. Patel explains. "There are hundreds of different species of bacteria that can infect patients and it's important to have the data to care for all of our patients, even if they are infected by unusual bacteria or have complicated types of infection."
Dr. Patel says her team plans to continue its sequencing efforts.
"Having the diagnostics and therapeutics to deal with a world of increasing numbers of antimicrobial-resistant bacteria will require a lot more sequencing and knowledge,” she says.