Biology subjects

Othmer, H. G.

Publications and source records attributed to Othmer, H. G..

3 recordsLinked to original sources

bioRxiv2023

Emergent Antibiotic Persistence in Cross-Feeding Bacteria in Structured Habitats

Antibiotic persistence allows a sub-population of bacteria to survive antibiotic-induced killing and contributes to the evolution of antibiotic resistance. Although bacteria typically live in microbial communities with complex ecological interactions, little is known about how microbial ecology affects antibiotic persistence. Here, we demonstrated that the combination of cross-feeding and community spatial structure can emergently cause high antibiotic persistence in bacteria by increasing the cell-cell heterogeneity in the metabolic state both during growth and antibiotic killing. We tracked the ampicillin-induced death on agar surfaces in a model obligate mutualism of Escherichia coli and Salmonella enterica. We found that E. coli formed [~]100-fold more antibiotic persisters in the cross-feeding coculture than in monoculture. This high persistence could not be explained solely by the presence of S. enterica, the presence of cross-feeding, or the growth rate differences between the mono- and co-cultures. Time-series fluorescent microscopy revealed increased cell-cell variation in E. coli lag time in the mutualistic co-culture. Furthermore, we discovered that an E. coli cell can survive antibiotic killing if the nearby S. enterica cells on which it relies die first--a mechanism we termed "dynamical loss of access to nutrient." In conclusion, we showed that the high antibiotic persistence phenotype can be an emergent phenomenon caused by a combination of cross-feeding and spatial structure. Our work highlights the importance of considering spatially-structured interactions during antibiotic treatment and to understand microbial community resilience more broadly.

microbiology↗

bioRxiv2019

Head Mesoderm Tissue Growth, Dynamics and Neural Crest Cell Migration

Vertebrate head morphogenesis involves orchestrated cell growth and tissue movements of the mesoderm and neural crest to form the distinct craniofacial pattern. To better understand structural birth defects, it is important that we learn how these processes are controlled. Here, we examine this question during chick head morphogenesis using time-lapse imaging, computational modeling, and experiment. We find that head mesodermal cells are inherently dynamic in culture and alter cell behaviors in the presence of either ectoderm or neural crest cells. Mesodermal cells in vivo display large-scale whirling motions that rapidly transition to lateral, directed movements after neural crest cells emerge. Computer model simulations predict distinct changes in neural crest migration as the spatio-temporal growth profile of the mesoderm is varied. BrdU-labeling and photoconversion combined with cell density measurements then reveal non-uniform mesoderm growth in space and time. Chemical inhibition of head mesoderm proliferation or ablation of premigratory neural crest alters mesoderm growth and neural crest migration, implying a dynamic feedback between tissue growth and neural crest cell signaling to confer robustness to the system.\n\nSummary StatementDynamic feedback between tissue growth and neural crest cell migration ensures robust neural crest stream formation and head morphogenesis shown by time-lapse microscopy, mathematical modeling and embryo perturbations.

developmental biology↗

bioRxiv2017

A model for autonomous and non-autonomous effects of the Hippo pathway in Drosophila

While significant progress has been made toward understanding morphogen-mediated patterning in development from both the experimental and the theoretical side, the control of size and shape of tissues and organs is poorly understood. Both involve adjustment of the scale of gene expression to the size of the system, but how growth and patterning are coupled to produce scale invariance and how molecular-level information is translated into organ- and organism-level functioning is one of the most difficult problems in biology. The Hippo pathway, which controls cell proliferation and apoptosis in Drosophila and mammalian cells, contains a core kinase mechanism that affects control of the cell cycle and growth. Studies involving over- and under-expression of components in the morphogen and Hippo pathways in Drosophila reveal conditions that lead to over- or undergrowth. Herein we develop a mathematical model that incorporates the current understanding of the Hippo signal transduction network and which can explain qualitatively both the observations on whole-disc manipulations and the results arising from mutant clones. We find that a number of non-intuitive experimental results can be explained by subtle changes in the balances between inputs to the Hippo pathway. Since signal transduction and growth control pathways are highly conserved across species, much of what is learned about Drosophila applies in higher organisms, and may have direct relevance to tumor dynamics in mammalian systems.

biophysics↗