Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial Cells
Abstract Antibiotic therapy and host cells frequently fail to eliminate invasive bacterial pathogens due to the emergence of antibiotic resistance, resulting in the relapse and recurrence of infections. Bacteria evolve various strategies to persist and survive in epithelial cells, a front‐line barri...
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Online Access: | https://doi.org/10.1002/advs.201900840 |
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doaj-e7b0a7975f0e4fac915c4748c1af69f12020-11-25T02:35:51ZengWileyAdvanced Science2198-38442020-09-01718n/an/a10.1002/advs.201900840Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial CellsXiaoye Liu0Fei Liu1Shuangyang Ding2Jianzhong Shen3Kui Zhu4Beijing Advanced Innovation Center for Food Nutrition and Human Health College of Veterinary Medicine China Agricultural University No. 2 Yuanmingyuan West Road Beijing 100193 ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health College of Veterinary Medicine China Agricultural University No. 2 Yuanmingyuan West Road Beijing 100193 ChinaNational Center for Veterinary Drug Safety Evaluation College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health College of Veterinary Medicine China Agricultural University No. 2 Yuanmingyuan West Road Beijing 100193 ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health College of Veterinary Medicine China Agricultural University No. 2 Yuanmingyuan West Road Beijing 100193 ChinaAbstract Antibiotic therapy and host cells frequently fail to eliminate invasive bacterial pathogens due to the emergence of antibiotic resistance, resulting in the relapse and recurrence of infections. Bacteria evolve various strategies to persist and survive in epithelial cells, a front‐line barrier of host tissues counteracting invasion; however, it remains unclear how bacteria hijack cellular responses to promote cytoplasmic survival under antibiotic therapy. Here, it is demonstrated that extracellular bacteria show invasive behavior and survive in epithelial cells in both in vivo and in vitro models, to increase antibiotic tolerance. In turn, sublethal levels of antibiotics increase bacterial invasion through promoting the production of bacterial virulence factors. Furthermore, antibiotic treatments interrupt lysosomal acidification in autophagy due to the internalized bacteria, using Bacillus cereus and ciprofloxacin as a model. In addition, it is found that sublethal levels of ciprofloxacin cause mitochondrial dysfunction and reactive oxygen species (ROS) accumulation to impair lysosomal vascular tape ATPase (V‐ATPase) to further promote bacterial persistence. Collectively, these results highlight the potential of host cells mediated antibiotic tolerance, which markedly compromises antibiotic efficacy and worsens the outcomes of infection.https://doi.org/10.1002/advs.201900840antibioticantibiotic toleranceautophagybacteriaepithelial cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaoye Liu Fei Liu Shuangyang Ding Jianzhong Shen Kui Zhu |
spellingShingle |
Xiaoye Liu Fei Liu Shuangyang Ding Jianzhong Shen Kui Zhu Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial Cells Advanced Science antibiotic antibiotic tolerance autophagy bacteria epithelial cells |
author_facet |
Xiaoye Liu Fei Liu Shuangyang Ding Jianzhong Shen Kui Zhu |
author_sort |
Xiaoye Liu |
title |
Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial Cells |
title_short |
Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial Cells |
title_full |
Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial Cells |
title_fullStr |
Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial Cells |
title_full_unstemmed |
Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial Cells |
title_sort |
sublethal levels of antibiotics promote bacterial persistence in epithelial cells |
publisher |
Wiley |
series |
Advanced Science |
issn |
2198-3844 |
publishDate |
2020-09-01 |
description |
Abstract Antibiotic therapy and host cells frequently fail to eliminate invasive bacterial pathogens due to the emergence of antibiotic resistance, resulting in the relapse and recurrence of infections. Bacteria evolve various strategies to persist and survive in epithelial cells, a front‐line barrier of host tissues counteracting invasion; however, it remains unclear how bacteria hijack cellular responses to promote cytoplasmic survival under antibiotic therapy. Here, it is demonstrated that extracellular bacteria show invasive behavior and survive in epithelial cells in both in vivo and in vitro models, to increase antibiotic tolerance. In turn, sublethal levels of antibiotics increase bacterial invasion through promoting the production of bacterial virulence factors. Furthermore, antibiotic treatments interrupt lysosomal acidification in autophagy due to the internalized bacteria, using Bacillus cereus and ciprofloxacin as a model. In addition, it is found that sublethal levels of ciprofloxacin cause mitochondrial dysfunction and reactive oxygen species (ROS) accumulation to impair lysosomal vascular tape ATPase (V‐ATPase) to further promote bacterial persistence. Collectively, these results highlight the potential of host cells mediated antibiotic tolerance, which markedly compromises antibiotic efficacy and worsens the outcomes of infection. |
topic |
antibiotic antibiotic tolerance autophagy bacteria epithelial cells |
url |
https://doi.org/10.1002/advs.201900840 |
work_keys_str_mv |
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