Evolving together, evolving apart: probing the genomic basis of a facultative host-microbe mutualism

The Burghardt lab at Penn State University studies the evolution of host-microbe mutualisms. Unlike obligate pathogens, mechanisms and rules governing facultative, mutualistic symbiosis remain largely unexplored. These relationships are characterized by the ability of each partner to survive independently, live in close physical proximity, and provide benefits to the other. Increasingly, mutualisms are recognized as crucial in protecting and maintaining host health. However, we still have limited knowledge of host genes that influence microbial adaptation, the impact of microbial generations outside hosts, and how mutualisms persist in nature. My lab creates new insights into the genomics of microbe-host interactions by utilizing whole- genome sequencing methods, innovative bioinformatics tools, and field and lab experiments. To achieve this goal, we harness the mutually beneficial symbiotic relationship between leguminous plants and rhizobial bacteria. This symbiosis is established when soil-dwelling bacteria invade root hairs and trigger the development of specialized structures called nodules, which can contain hundreds of millions of bacteria. Inside nodules, the bacteria convert atmospheric nitrogen into a form that plants can utilize, while the plants supply the bacteria with abundant sugars produced during photosynthesis. Most of the bacterial population at any given time lives in the soil and the symbiosis is established anew for each plant generation. Thus, these bacteria are exposed to soil selection and multiple hosts, allowing us to study the effects of host and soil variation on mutualism evolution. Our model system is Medicago truncatula and Sinorhizobium meliloti, which have a long history of functional genetic advancements. My lab is uniquely suited to pursue the work as it houses significant collections of sequenced isolates and host accessions. This rich toolkit allows the examination of plant and bacterial genes simultaneously, providing a clear path for the validation of bacterial genes underlying host fitness and vice versa. Another key feature is that the hosts specifically enrich a single species of bacteria enabling cost-effective whole-genome sequencing to monitor strain competitive fitness in laboratory experiments and changes in allele frequency in the field. Over the next five years, I will lead projects on three themes: 1) characterizing the function of and inferring selection on genes underlying bacterial fitness within hosts; 2) examining the interplay between adaptation to host and non-host environments; and 3) identifying the mechanisms behind the evolution of mutualism. Results from this research program will provide insights into the genetic mechanisms of beneficial host-microbe interactions, offering clues for understanding gene function in less tractable systems. In addition, results will establish a framework for predicting if evolution outside of a host will undermine or facilitate host adaptation and uncover the selectivity and reward mechanisms underlying mutualism persistence. Ultimately, this research advances our ability to deploy beneficial microbes to enhance overall host health across systems. Project Number: 1R35GM162124-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Liana Burghardt | Institution: PENNSYLVANIA STATE UNIVERSITY, THE, UNIVERSITY PARK, PA | Award Amount: $393,250 | Activity Code: R35 | Study Section: Maximizing Investigators' Research Award A Study Section[MRAA] View on NIH RePORTER: https://reporter.nih.gov/project-details/11270190