Benjamin Kaisha N, Goyal Aditi, Nair Ramesh V, Endy Drew
Bioengineering, Stanford University, Stanford, CA, United States.
Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, United States.
Front Microbiol. 2024 Jul 22;15:1408796. doi: 10.3389/fmicb.2024.1408796. eCollection 2024.
Skin serves as both barrier and interface between body and environment. Skin microbes are intermediaries evolved to respond, transduce, or act in response to changing environmental or physiological conditions. We quantified genome-wide changes in gene expression levels for one abundant skin commensal, , in response to an internal physiological signal, glucose levels, and an external environmental signal, temperature. We found 85 of 2,354 genes change up to 34-fold in response to medically relevant changes in glucose concentration (0-17 mM; adj ≤0.05). We observed carbon catabolite repression in response to a range of glucose spikes, as well as upregulation of genes involved in glucose utilization in response to persistent glucose. We observed 366 differentially expressed genes in response to a physiologically relevant change in temperature (37-45°C; adj ≤ 0.05) and an heat-shock response that mostly resembles the heat-shock response of related staphylococcal species. DNA motif analysis revealed CtsR and CIRCE operator sequences arranged in tandem upstream of and operons. We identified and curated 38 glucose-responsive genes as candidate ON or OFF switches for use in controlling synthetic genetic systems. Such systems might be used to instrument the skin microbiome or help control microbes bioengineered to serve as embedded diagnostics, monitoring, or treatment platforms.
皮肤是身体与环境之间的屏障和界面。皮肤微生物是进化而来的媒介,可对不断变化的环境或生理条件做出反应、进行信号转导或采取行动。我们对一种丰富的皮肤共生菌——[具体菌种名称缺失],在响应内部生理信号(葡萄糖水平)和外部环境信号(温度)时,全基因组范围内的基因表达水平变化进行了量化。我们发现,在葡萄糖浓度发生与医学相关的变化(0 - 17 mM;校正P值≤0.05)时,2354个基因中的85个基因变化幅度高达34倍。我们观察到,在一系列葡萄糖峰值刺激下会出现碳代谢物阻遏现象,以及在持续葡萄糖刺激下参与葡萄糖利用的基因上调。我们观察到,在温度发生生理相关变化(37 - 45°C;校正P值≤0.05)时,有366个差异表达基因,以及一种热休克反应,该反应大多类似于相关葡萄球菌属物种的热休克反应。DNA基序分析揭示,在[具体基因名称缺失1]和[具体基因名称缺失2]操纵子上游串联排列着CtsR和CIRCE操纵序列。我们鉴定并整理了38个葡萄糖响应基因,作为用于控制合成遗传系统的候选开启或关闭开关。此类系统可用于检测[具体菌种名称缺失]皮肤微生物群,或有助于控制经生物工程改造以用作嵌入式诊断、监测或治疗平台的微生物。