Clinical microbiology at Mayo Clinic: A look back and ahead
Mayo Clinic’s clinical microbiology laboratories are internationally renowned for offering reference and assay development expertise in all areas of conventional and molecular medical microbiology. Led by faculty specializing in bacteriology, mycobacteriology, virology (including hepatitis viruses and HIV), parasitology, infectious diseases serology, mycology, molecular diagnostics, specimen processing, and media preparation, the laboratories offer a broad selection of tests designed to quickly identify and characterize causative agents of infectious diseases.
The field of clinical microbiology has a long and distinguished history at Mayo Clinic. Since the early 1900s, the clinical microbiology team has played important and leading roles in advancing testing and patient care. Through the years, the group developed and implemented many new groundbreaking culture techniques, immunoassays, and antimicrobial susceptibility testing and molecular methods to detect, identify, and characterize microbial pathogens and provide guidance for their treatment.
Mayo Clinic’s Clinical Microbiology Laboratory was founded in 1911 at Mayo Clinic Hospital, Saint Marys Campus. It initially resided in the Department of Clinical Pathology and consisted of bacteriology, parasitology, and infectious diseases serology testing. At that time, the top five causes of death in the United States were diseases of the heart, tuberculosis, pneumonia (including influenza), nephritis, and stroke.
This was the golden age of clinical microbiology. Robert Koch had just proved the germ theory of disease, and scientists rushed to identify the agents of many common infectious diseases. The Clinical Microbiology Laboratory at Mayo Clinic was able to detect these agents in clinical specimens and provide results to Mayo Clinic physicians to diagnose patients and guide clinical care.
In 1911, Mayo Clinic’s Microbiology Laboratory performed a total of 554 stool examinations, 985 sputum examinations, 200 cultures, 31 blood parasite examinations, 771 Wassermann tests (the first blood test for syphilis), and 29 animal inoculations.
The laboratories continued to grow and moved to the newly constructed Plummer Building in downtown Rochester, Minnesota, in the 1930s. In 1945, microbiology became its own department, comprised of the bacteriology and parasitology laboratories. In the next few years, separate mycology and mycobacteriology laboratories also were established. The Clinical Microbiology Laboratory made many advances in the field during this time, including the development of the Inhibitory Mold Agar by John Ulrich, Ph.D., in 1952, which is still widely used today for growing fungi, and the founding of the Clinical Virology Laboratory in 1961 by Ernest Herrmann, Ph.D. Mayo Clinic’s Clinical Virology Laboratory was the first of its kind in the United States, providing routine, rapid, and specific virology services based on the use of cell cultures for diagnosis of viral infections. This was also around the time that Alfred Karlson, Ph.D., developed an animal model for determining susceptibility of Mycobacterium tuberculosis to commonly used antimycobacterial drugs.
The modern era of clinical microbiology at Mayo Clinic began in 1972 under the leadership of John Washington II, M.D., who introduced scientifically based standards of practice and carried out research and assay development studies that advanced the science. The training of postdoctoral fellows also became an important part of Mayo Clinic’s education shield during this time. Training in the competitive American Board of Medical Microbiology and American Board of Pathology programs continues to be an area of importance for the practice, with many trainees going on to have long and distinguished careers in clinical microbiology at institutions throughout the world.
The division moved to the fourth floor of the newly constructed Hilton Building in 1974, where it continued to expand and innovate. Pathologist C. Terrence Dolan, M.D., completed his training at Mayo Clinic during the 1970s and later became director of Mayo’s Clinical Mycology Laboratory. Among other innovations, he developed a simplified approach for identifying yeasts using cornmeal agar and a combination of biochemical tests. Dr. Dolan’s innovative approaches were soon adopted by other laboratories before commercially available testing methods became available.
Also during the 1970s, Thomas F. Smith, Ph.D., a Mayo Clinic postdoctoral trainee who went on to become chair of the Division of Clinical Microbiology in 1991, expanded the lab’s testing menu to include assays for the laboratory diagnosis of Chlamydia trachomatis in cell cultures. Lyle Weed, M.D., Ph.D., a pathologist and chair of Mayo Clinic’s Division of Clinical Microbiology, worked with Dr. Smith to standardize testing methods for detecting C. trachomatis, establishing the first laboratory test in the United States for the diagnosis of C. trachomatis infection. This bacterial infection is now recognized as the most prevalent sexual transmitted disease in the world.
During the 1980s, Dr. Smith, with help from research technologist Curt Gleaves, developed the “shell vial assay,” which combined monoclonal antibodies to detect early antigens of viruses like cytomegalovirus in cell culture. This method revolutionized the field of clinical virology by reducing the diagnostic turnaround time of many viral infections from several days to 18-24 hours, and became standard practice around the world. Advances were also occurring in the mycobacteriology and mycology laboratories under the directorship of Glenn D. Roberts, Ph.D. Notable developments included the creation of the rapid selective urease test for identifying Cryptococcus neoformans and the rapid assimilation of trehalose test for Candida glabrata. Dr. Roberts and Leslie Hall also published the first evaluation of the isolator blood culture system for recovery of fungi in blood, and evaluated the lysis-centrifugation system for recovery of yeasts and filamentous fungi from blood.
In her December 2021 article for Clinical Chemistry, “Advances in Testing for Infectious Diseases —Looking Back and Projecting Forward,” Robin Patel, M.D., co-director of Mayo Clinic’s Bacteriology Laboratory and chair of the Division of Clinical Microbiology from 2010 to 2020, writes that the invention of the polymerase chain reaction (PCR) test in 1983 served to effectively “divide microbial diagnostics into those originating before (e.g., culture, stains, and antigen and antibody detection) and those available after the advent of what is today better referred to as nucleic acid amplification tests (NAATs), of which PCR is one example.” PCR testing was put into clinical practice at Mayo Clinic during the 1990s. Today, PCR assays developed by Mayo Clinic’s Clinical Microbiology team continue to allow innovative diagnoses, oftentimes without a need for the invasive procedures required in the past.
Robin Patel, M.D.
In 2005, “while attempting to develop an assay to detect the then recently emerged Clostridioides difficile strain BI/NAP1/027,” Dr. Patel writes that she and others at Mayo Clinic “were surprised to observe that the generated data showed that the antigen test we had been using to diagnose C. difficile had low sensitivity.” This discovery led Mayo Clinic to implement stool PCR testing for C. difficile in 2007, which has proved to be a fast and accurate testing method. Mayo Clinic was one of the first institutions in the world to adopt stool testing for infectious agents using PCR. Dr. Patel and her team also developed a multiplex stool PCR assay for agents of gastroenteritis, an approach that has now been commercialized by many companies and is broadly used worldwide.
Another important advancement that occurred in the field of clinical microbiology, and one that Dr. Patel says she and other microbiologists “didn’t see coming,” was the use of mass spectrometry to identify bacteria and fungi grown in culture. After seeing the technology in use for the first time during a medical conference in 2009, Dr. Patel brought it to Mayo Clinic in 2010 and helped put it into clinical practice a year later, making Mayo Clinic just the second institution in the U.S. to offer mass spectrometry testing for bacterial identification clinically. “This technology completely changed identification of bacteria and fungi, ridding our clinical laboratory of a number of manual biochemical/conventional identification techniques,” she writes. “This technology is cost-effective, saving money for the laboratory and by inference, our patients.”
The invention and use of next generation sequencing have also brought “welcomed changes” to clinical microbiology, Dr. Patel says. “We have used this technology to identify outbreaks and to show that, in some cases, what appeared to be outbreaks were not,” she writes. “We also showed that the whole-genome sequences of bacterial isolates can be used to predict phenotypic antibiotic susceptibility.”
While these and other advancements that have taken place throughout the history of clinical microbiology have no doubt helped to improve patient care, Dr. Patel says there is still more work to be done.
“Almost every day, in my daily clinical work, I am presented with good quality and clinically significant sequence data representing microorganisms not yet named; this is a challenge from a clinical standpoint as such identifications cannot be properly interpreted and reported. So, we need more basic work in microbial genomics,” she writes.
Dr. Patel also notes that the high cost of sequencing continues to be “a barrier to its widespread adoption, at least in the clinical microbiology field,” and that the turnaround times of many tests are still “less than ideal.”
You can read Dr. Patel’s full article here.
Today, Mayo Clinic’s Division of Clinical Microbiology is comprised of seven laboratories across three locations. The division employs seven consultants/laboratory directors, more than 370 staff, and performed more than 4 million tests during 2021.