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Advancing Clinical & Public Health Using Teams and Tech

In the last few years, the (re)emergence of several pathogens has kept clinical and public health microbiologists on their toes, balancing the development of rapid diagnostics, therapeutics and vaccines with planning for long-term infection prevention efforts. To solve current and future health-related challenges, professionals are calling for team-based science and an interdisciplinary research approach.

Interdisciplinary investigations produce robust research that benefits patients and their environments—leading to new drugs, devices and preventive medical interventions that directly improve the health and well-being of society. “Our mission as clinical microbiologists and as public health microbiologists is to have an impact on patients and the population. This grounds us in guiding the work that we do and the innovations we try to create,” said . “That can come across as new or better diagnostic testing or as better characterizing the infection to enable improved management of the infection.”

Why Team Science?

Team science and leverages the diverse strengths and expertise of scientists who may typically pursue scientific endeavors separately. In clinical and public health spheres, this might involve collaboration between clinicians, practicing physicians, medical microbiologists and pharmacists who work jointly on a research initiative and discuss subsequent implementation and best practices in health care spaces. Examples of effective partnerships of this nature might consist of scientists working on basic translational studies or microbiologists trying to understand how the microbiome relates to diagnostic and prognostic implications in clinical studies. “All of these teams include people who understand and generate the data in the lab, as well as people who see patients,” said A. Krishna Rao, M.D., M.S., Associate Professor of Infectious Diseases and Internal Medicine at the University of Michigan and track lead for Clinical Infections and Vaccines (CIV) at ��������appMicrobe 2023. Team science was the focus of the ��������appMicrobe 2023 session, “."

 Krishna Rao, M.D., M.S., investigated why some patients colonized with K. pneumoniae develop an infection, while other patients remain asymptomatically colonized by K. pneumoniae.
Source: Wikimedia CommonsRao experienced the benefits of team science firsthand through his research on Klebsiella pneumoniae, a bacterium that is often the causative agent of health care-associated infections (HAIs). At the University of Michigan, Rao worked alongside , a trained microbiologist and pathologist, who has a particular interest in the genomics and virulence determinants of K. pneumoniae. Prior to teaming up with Rao, Bachman was investigating a hypothesis about the relationship between K. pneumoniae genetics and the outcomes of infection. “He wanted to test this [hypothesis] in patient samples, but he didn’t have the necessary clinical expertise,” Rao explained. “So, he partnered with me, a clinician who has training in biostatistics and clinical research, and someone who knows how to design an observational research study.” Together, the research pair pursued multiple inquiries and published several papers.

"My overall strategy for success is to get people who don't have the same expertise but have a shared goal [or] interest—get them talking early, keep the lines of communication open and make it so everyone feels like they have a piece of the project," he said.

One paper resulting from the collaboration between Rao and Bachman , while other patients remain asymptomatically colonized by K. pneumoniae. The team hypothesized that the genetics of the infecting K. pneumoniae strain played a role in this outcome—some strains harbored genes that increased virulence. With this in mind, Rao and Bachman proposed a case-control study, isolating K. pneumoniae from rectal swabs collected from patients. “[For the case-control study], we matched cases to controls, and adjusted for a whole bunch of clinical factors (e.g., hemoglobin level, white blood cell count) that could explain the differences between cases and controls,” Rao said. “When we found the [bacterial] genes that were enriched, we could have some increased confidence that these genes were actually independently associated with the risk of infection—not just confounded by the clinical factors.”

Further investigation included locating 5 of these “gene hits,” or bacterial loci, in K. pneumoniae and conducting phylogenetic analysis to determine that the hits were not just but did, in fact, serve as predictors for clinical infection. The research team also knocked out K. pneumoniae genes of interest and, subsequently, used a mouse model of pneumonia to determine how the loss of those genes impacted the pathogen’s ability to cause infection. “In the case of one [of the animal models], the severity of the infection was reduced," Rao explained. “Then, [Bachman] did a complementation assay and put the gene back in [K. pneumoniae] and reinfected the mouse.” Sure enough, this restored the ability of the bacterium to cause disease. In clinical practice, this knowledge can help providers identify patients who are at a higher risk of K. pneumoniae infections. Essentially, medical microbiologists could use diagnostic assays to screen for the identified genes and, ultimately, predict which patients are most at risk for developing infection. Identifying high-risk patients would ensure that preventive interventions or rapid treatments get administered.

“What’s cool about this paper is [that] not one of the authors can explain the entirety of the manuscript alone,” Rao said. “It's not like I understand the nuances of the phylogenetic tree and the genomics; that's not my training and background. And it's not like Michael can explain how and why we did the matching and the additional logistic regression that we did for the case control study and analysis. But it's a classic case of the whole being greater than the sum of the parts.”

Barriers to Collaboration

Still, even with its numerous benefits, team science isn’t always instinctual. Rao noted that when scientists embark upon their next clinical or public health investigation, structural barriers may hinder collaborative efforts in STEM fields. For example, promotion committees often prioritize first-author publications and last-author publications for senior and junior researchers, respectively, with authorship coming from researchers within a single institution. “There are still many institutions and many scientists who have that traditional view that the research that comes out of their lab is their lab’s research. Their idea of collaboration might be, ‘Hey, I'll let you use this instrument,' or 'I'll send you a strain,’” Rao said. But Rao noted some publishers, , are starting to include co-first and co-senior authors from different institutions or departments.

Emerging Technologies Fuel Teamwork

New technologies in clinical and public health spaces could also mean faster turnaround times for testing, improved patient care and greater opportunities for experts to collaborate, according to Robert Tibbetts, Ph.D., Associate Director of a clinical microbiology laboratory for Henry Ford Health System and track lead for Clinical and Public Health Microbiology (CPHM) at ��������appMicrobe 2023. In particular, Tibbetts highlighted notable technologies, including new processes for automation, rapid antimicrobial resistance susceptibility testing and next-generation sequencing (NGS), all of which benefit and bring multiple professions—from medical technologists to epidemiologists—together to problem-solve.

"Clinical public health covers everything from veterinary sciences, environmental microbiology, global health and One Health,” Tibbetts said. “Medical technologists, clinicians and physicians encompass infection prevention and public health—it's a collaboration with various vendors and companies that are making these tests, or that are assisting with analytics. It's not just a matter of doing a test and putting out a result; it really does encompass a large group of people working behind the scenes to get these assays developed and useful for the patients.”

An Interdisciplinary Approach to NGS

NGS has grown in popularity in recent years among clinical and public health researchers, due to the technology’s ability to answer questions using genome assembly and metagenomic analysis. “One of the most exciting things right now is the use of next-generation sequencing or whole-genome sequencing. In the clinical lab, it certainly could be a game-changer when it comes to rapid diagnostics,” Tibbetts said. At ��������appMicrobe 2023, the session "” delved into the debate surrounding the inclusion of whole genome sequencing results in patient records and care coordination. 

Jennifer Guthrie, Ph.D., Assistant Professor in the Department of Microbiology & Immunology and Epidemiology and Biostatistics at Western University in Ontario, Canada, utilizes whole-genome sequencing to understand pathogens. By combining genomic information with additional laboratory testing and clinical diagnostic information, Guthrie performs pathogen surveillance and monitoring to ascertain important information about disease transmission and outbreaks. She can even look for antimicrobial resistance genes in bacteria. Her research benefits from an interdisciplinary approach to scientific investigation, with researchers collaborating from a variety of different fields, including epidemiology, public health, bioinformatics and genomics. The mission behind this collaborative work is rooted in providing rapid, evidence-based solutions to protect population health.

When SARS-CoV-2 first emerged and transmission of the virus wasn’t fully understood, Guthrie recalled . Guthrie noted that, oftentimes, in long-term care facilities, bathrooms are shared between residents, and uncertainty regarding fomite transmission left housing setups in question. “We don't always have a lot of spare rooms to move patients into, so we wanted to [investigate risks through] genome sequencing and determine whether there was transmission [of SARS-CoV-2] between shared washroom pairs,” she explained. “We determined that we could leave individuals [sharing a washroom] where they [were], whereas roommates sharing a room were obviously at risk for transmission [because of exposure to respiratory droplets].” Based on these findings, residents of long-term care facilities continued to share bathrooms and maintained separate bedrooms.

Typically, the order of operations for NGS for infectious disease investigation involves an initial request sent to a public health lab, followed by the collection of samples and, finally, performance of the actual genome sequencing. Guthrie pointed to the large number of professionals involved in executing these core steps. At the outset, epidemiologists are tasked with tracking and tracing a particular pathogen and entering all the contact information into a central provisional database, which can then be paired with data collected by experts in genomics. This collaboration helps determine whether transmission of a pathogen occurred in a particular area. It also provides insight into how and where the pathogen spread. Finally, that data gets sent to local public health professionals who rely on the information to develop policies to protect the health of their community.

“We've got quite a system going [across multiple fields] to be able to do this work and manage an assignment and outbreak identification,” Guthrie added. At ��������appMicrobe 2023, teams of scientists working in clinical and public health microbiology examined how commercial sequencing technologies can be leveraged for clinical diagnostics during the session, ""

��������appMicrobe 2023: Fostering Connecting, Collaboration and Better Science

At ��������appMicrobe 2023 in Houston, Texas, scientists at all career stages connected with professionals from multiple fields. As Rao summarized, ��������appMicrobe benefits society by fostering research collaboration. "[It gets] scientists out of their labs and into a conference to talk to each other," he said. "That makes for better science, and it makes for a better research community. Whenever any society invests in science, it reaps the rewards tenfold."

Learn More About ��������appMicrobe 2023

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In This Issue:

• The Power of Microbial Sciences to Change the World
• Climate Change Experts Tap Microbes to Protect the Planet
• Antimicrobial Resistance: Facing Tomorrow's Problems, Today
• Friends and Foes: Microbial Interactions and Infection
• Advancing Clinical & Public Health Using Teams and Tech
• Part of Our World: Microbial Biodiversity Drives Innovation
• Microbiology Professionals Impact All Facets of Society
• What's Hot in the Microbial Sciences