Xianyi Xiong is a Post-Master’s Researcher and Lab Manager advised by Professor Will Harcombe at the University of Minnesota (USA), where he earned his bachelor’s and master’s degrees. He is an incoming PhD student at MIT. His research lies in the intersection among bacterial systems biology, microbial ecology, and stress biology. His goal is to continue strengthening the link among these fields by (1) using systems biology approaches to predict ecological dynamics of microbial communities under perturbations, and (2) using community ecology theory and experiments to investigate how emergent patterns arise in microbial communities facing perturbations. His research strategy is to develop high-throughput data analysis methods and large-scale mathematical models to gain mechanistic insights on emergent patterns in microbial communities. So far, his research has been published in journals like ISME Journal, Soil Biology and Biochemistry, and Frontiers in Microbiology.
Abstract
How life responds to and persists through perturbations in the environment is a central question in biology. In microbiology, it is a pressing task to understand the strategy of bacteria to persist through the antibiotic perturbation, which in turn can help humanity tackle the global public health crisis of antibiotic resistance. It became recognized over the past decades that bacteria in nature tend to engage in complex ecological interactions, and that microbial ecology can influence responses to the antibiotic drugs. However, little attention has been dedicated to the cross-feeding ecological interaction, where bacteria secrete nutrient for each other to grow.
In this talk, I will discuss recent progress developing simple yet high-throughput, systems biology methods and mathematical models to study the stress biology of cross-feeding bacteria. We focused on a synthetic cross-feeding community between Escherichia coli and Salmonella enterica that exchange an amino acid and carbon. First, we demonstrated that the combination of cross-feeding and the community spatial structure can emergently cause high antibiotic persistence, which allows a subpopulation of bacteria to survive antibiotic-induced killing. Using fluorescent microscopy to track single-cell death on a surface, we found that an E. coli cell can survive the ampicillin-induced killing if the nearby S. enterica cells on which it relies die first. This work reveals an ecological mechanism regulating antibiotic persistence and argues for the importance to consider spatially structured interactions in studying stress biology.
Finally, we showed in a separate research that cross-feeding frequently favors less synergistic interactions in many pairwise antibiotic stressors against the growing E. coli. When two or more antibiotics are used simultaneously to treat bacterial infections, the antibiotics can interact synergistically (antagonistically) to produce a combined effect that is better (worse) than expected from each single drug. By combining high-throughput growth assays, HPLC assays, and genome-scale metabolic models, we found that the sulfamethoxazole-trimethoprim combination can cause E. coli to oversecrete carbon to promote community growth, change species ratios, and reduce synergistic interactions between antibiotics. Together, both research projects investigated how the interactions between ecological factors or between antibiotic stressors can produce emergent properties in microbial communities facing perturbation.
