{"title":"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。","authors":"Ruixue Zhang, Christopher Hartline, Fuzhong Zhang","doi":"10.1128/msystems.01295-24","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>Escherichia coli</i> 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 (<i>R</i><sup>2</sup> = 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.</p><p><strong>Importance: </strong>This research delves into the intriguing realm of bacterial persistence and its profound implications for biofilms, infections, and antibiotic efficacy. The study focuses on <i>Escherichia coli</i> 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.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The ability in managing reactive oxygen species affects <i>Escherichia coli</i> persistence to ampicillin after nutrient shifts.\",\"authors\":\"Ruixue Zhang, Christopher Hartline, Fuzhong Zhang\",\"doi\":\"10.1128/msystems.01295-24\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>Escherichia coli</i> 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 (<i>R</i><sup>2</sup> = 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.</p><p><strong>Importance: </strong>This research delves into the intriguing realm of bacterial persistence and its profound implications for biofilms, infections, and antibiotic efficacy. The study focuses on <i>Escherichia coli</i> 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.</p>\",\"PeriodicalId\":18819,\"journal\":{\"name\":\"mSystems\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2024-10-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"mSystems\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1128/msystems.01295-24\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"mSystems","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1128/msystems.01295-24","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
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.
mSystemsBiochemistry, 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.