管理活性氧的能力会影响大肠埃希菌在营养物质转换后对氨苄西林的耐受性。

IF 5 2区 生物学 Q1 MICROBIOLOGY mSystems Pub Date : 2024-10-29 DOI:10.1128/msystems.01295-24
Ruixue Zhang, Christopher Hartline, Fuzhong Zhang
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引用次数: 0

摘要

细菌的持久性对生物膜、感染和抗生素的有效性有着深远的影响。自然环境中普遍存在的营养物质转移会极大地促进宿主的形成。然而,人们对促进宿主形成的机制仍然知之甚少。在这里,我们研究了大肠埃希菌从各种碳源转为脂肪酸后的存活频率,观察到了截然不同的存活率。甘油转化为油酸(GLY → OA + AMP)后,超过 99.9% 的细胞在 24 小时的氨苄西林(AMP)处理中死亡,而葡萄糖转化为油酸(GLU → OOA + AMP)后,竟然有 56% 的细胞在相同的抗生素处理中存活下来。利用单细胞成像和延时显微镜相结合的方法,我们发现 AMP 诱导高水平的活性氧(ROS)是细胞从葡萄糖碳酸转化为 OA + AMP 后被杀死的主要机制。此外,ROS爆发的时间(R2 = 0.91)与所有糖原碳化物的时间杀伤曲线中快速杀伤阶段的开始时间高度相关。然而,在 GLU → OA + AMP 转移之后,ROS 并没有积累到致死水平。我们还发现,氧化应激调节剂和 ROS 解毒酶的过度表达会强烈影响营养转换后的 ROS 数量和持续频率。这些发现阐明了各种营养物质转变所导致的不同持续频率,并强调了 ROS 的关键作用。我们的研究深入揭示了细菌持续存在的机制,为有效对抗细菌耐药性的靶向治疗干预带来了希望:本研究深入探讨了细菌持久性这一引人入胜的领域及其对生物膜、感染和抗生素疗效的深远影响。研究的重点是大肠杆菌,以及从不同碳源到脂肪酸的转换如何影响耐抗生素的持久性细菌细胞的形成。研究结果显示了存活率的惊人变化,从葡萄糖过渡到油酸后,大量细胞在氨苄青霉素处理中存活下来。关键的启示是活性氧(ROS)在细胞杀伤中的作用,特别是从葡萄糖碳转换后。ROS 爆发的时间与快速杀灭阶段一致,突出了氧化应激调节对持续频率的关键影响。这项研究为了解细菌的持续存在机制提供了宝贵的见解,为有针对性地采取治疗干预措施以有效对抗细菌耐药性提供了潜在的途径。
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The ability in managing reactive oxygen species affects Escherichia coli persistence to ampicillin after nutrient shifts.

Bacterial persistence profoundly impacts biofilms, infections, and antibiotic effectiveness. Persister formation can be substantially promoted by nutrient shift, which commonly exists in natural environments. However, mechanisms that promote persister formation remain poorly understood. Here, we investigated the persistence frequency of Escherichia coli after switching from various carbon sources to fatty acid and observed drastically different survival rates. While more than 99.9% of cells died during a 24-hour ampicillin (AMP) treatment after the glycerol to oleic acid (GLY → OA + AMP) shift, a surprising 56% of cells survived the same antibiotic treatment after the glucose to oleic acid (GLU → OOA + AMP) shift. Using a combination of single-cell imaging and time-lapse microscopy, we discovered that the induction of high levels of reactive oxygen species (ROS) by AMP is the primary mechanism of cell killing after switching from gluconeogenic carbons to OA + AMP. Moreover, the timing of the ROS burst is highly correlated (R2 = 0.91) with the start of the rapid killing phase in the time-kill curves for all gluconeogenic carbons. However, ROS did not accumulate to lethal levels after the GLU → OA + AMP shift. We also found that the overexpression of the oxidative stress regulator and ROS detoxification enzymes strongly affects the amounts of ROS and the persistence frequency following the nutritional shift. These findings elucidate the different persister frequencies resulting from various nutrient shifts and underscore the pivotal role of ROS. Our study provides insights into bacterial persistence mechanisms, holding promise for targeted therapeutic interventions combating bacterial resistance effectively.

Importance: This research delves into the intriguing realm of bacterial persistence and its profound implications for biofilms, infections, and antibiotic efficacy. The study focuses on Escherichia coli and how the switch from different carbon sources to fatty acids influences the formation of persister-resilient bacterial cells resistant to antibiotics. The findings reveal a striking variation in survival rates, with a significant number of cells surviving ampicillin treatment after transitioning from glucose to oleic acid. The key revelation is the role of reactive oxygen species (ROS) in cell killing, particularly after switching from gluconeogenic carbons. The timing of ROS bursts aligns with the rapid killing phase, highlighting the critical impact of oxidative stress regulation on persistence frequency. This research provides valuable insights into bacterial persistence mechanisms, offering potential avenues for targeted therapeutic interventions to combat bacterial resistance effectively.

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来源期刊
mSystems
mSystems Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
10.50
自引率
3.10%
发文量
308
审稿时长
13 weeks
期刊介绍: mSystems™ will publish preeminent work that stems from applying technologies for high-throughput analyses to achieve insights into the metabolic and regulatory systems at the scale of both the single cell and microbial communities. The scope of mSystems™ encompasses all important biological and biochemical findings drawn from analyses of large data sets, as well as new computational approaches for deriving these insights. mSystems™ will welcome submissions from researchers who focus on the microbiome, genomics, metagenomics, transcriptomics, metabolomics, proteomics, glycomics, bioinformatics, and computational microbiology. mSystems™ will provide streamlined decisions, while carrying on ASM''s tradition of rigorous peer review.
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