2024-11-15 カリフォルニア大学サンディエゴ校(UCSD)
<関連情報>
- https://today.ucsd.edu/story/researchers-uncover-achilles-heel-of-antibiotic-resistant-bacteria
- https://www.science.org/doi/10.1126/sciadv.adq5249
抗生物質耐性の生理的コスト: 細菌におけるリボソームの変異体からの洞察 Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria
Eun Chae Moon, Tushar Modi, Dong-yeon D. Lee, Danis Yangaliev, […], and Gürol M. Süel
Science Advances Published:15 Nov 2024
DOI:https://doi.org/10.1126/sciadv.adq5249
Abstract
Antibiotic-resistant ribosome variants arise spontaneously in bacterial populations; however, their impact on the overall bacterial physiology remains unclear. We studied the naturally arising antibiotic-resistant L22* ribosome variant of Bacillus subtilis and identified a Mg2+-dependent physiological cost. Coculture competition experiments show that Mg2+ limitation hinders the growth of the L22* variant more than the wild type (WT), even under antibiotic pressure. This growth disadvantage of L22* cells is not due to lower ribosome abundance but rather due to reduced intracellular Mg2+ levels. Coarse-grained elastic-network modeling of ribosome conformational dynamics suggests that L22* ribosomes associate more tightly with Mg2+ when compared to WT. We combined the structural modeling and experimental measurements in a steady-state model to predict cellular adenosine 5′-triphosphate (ATP) levels, which also depend on Mg2+. Experiments confirmed a predicted ATP drop in L22* cells under Mg2+ limitation, while WT cells were less affected. Intracellular competition for a finite Mg2+ pool can thus suppress the establishment of an antibiotic-resistant ribosome variant.
