频率依赖的生态相互作用增加了先前存在的药物耐药性的流行率,并塑造了分布
Jeff Maltas1,2, Dagim Shiferaw Tadele1,3, Arda Durmaz1
1Cleveland Clinic, Translational Hematology Oncology Research, Cleveland, Ohio 44195, USA.
以前存在的耐药性,在疟疾和癌症等疾病中很常见,由于频率依赖的生态相互作用而持续存在. 这些相互作用,其中耐药突变体从祖先的存在中受益,解释了耐药性如何演变和持续存在.
科学领域:
- 进化生物学 进化生物学
- 医学科学 医学科学 医学科学
- 数学生物学 数学生物学
背景情况:
- 耐药性是治疗传染病和癌症的一个主要挑战.
- 赋予耐药性的突变通常会产生适应性成本,但经常观察到先前存在的耐药性.
- 这种悖论的现有解释包括空间救援和突变供应,但并不完全考虑观测.
研究的目的:
- 调查频率依赖的生态相互作用在先前存在的药物耐药性的流行中的作用.
- 开发一个数学框架来分析这些相互作用对电阻演变的影响.
- 测试生态相互作用是先前存在的耐药性的主要驱动因素的假设.
主要方法:
- 数字模拟和分析近似被用来建模进化动态.
- 分析了耐药突变体和祖先细胞之间的频率依赖的生态相互作用.
- 非小细胞肺癌 (NSCLC) 的临床耐药机制经过基因工程,并对生态相互作用进行了测试.
主要成果:
- 生态相互作用显著扩大了预期存在耐药性的条件.
- 积极的生态相互作用,即使是弱的,也会大大增加耐药克隆的灭绝时间.
- 在NSCLC中设计的抵抗机制与祖先细胞呈现出积极的生态相互作用.
结论:
- 频率依赖的生态相互作用对于塑造先前存在的耐药性的进化动态至关重要.
- 这些相互作用可以改善抵抗的健身成本,促进其持久性.
- 了解这些生态动态对于开发针对抗药性疾病的有效治疗策略至关重要.
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