Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response

Background: Envelope stress responses (ESRs) are critical for adaptive resistance of Gram-negative bacteria to envelope-targeting antimicrobial agents. However, ESRs are poorly defined in a large number of well-known plant and human pathogens. Dickeya oryzae can withstand a high level of self-produ...

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Main Authors: Liang, Zhibin, Lin, Qiqi, Wang, Qingwei, Huang, Luhao, Liu, Huidi, Shi, Zurong, Cui, Zining, Zhou, Xiaofan, Gao, Yong-Gui, Zhou, Jianuan, Zhang, Lian-Hui, Deng, Yizhen
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/169682
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Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-169682
record_format dspace
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Chlorhexidine
Envelope Stress Response
spellingShingle Science::Biological sciences
Chlorhexidine
Envelope Stress Response
Liang, Zhibin
Lin, Qiqi
Wang, Qingwei
Huang, Luhao
Liu, Huidi
Shi, Zurong
Cui, Zining
Zhou, Xiaofan
Gao, Yong-Gui
Zhou, Jianuan
Zhang, Lian-Hui
Deng, Yizhen
Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response
description Background: Envelope stress responses (ESRs) are critical for adaptive resistance of Gram-negative bacteria to envelope-targeting antimicrobial agents. However, ESRs are poorly defined in a large number of well-known plant and human pathogens. Dickeya oryzae can withstand a high level of self-produced envelope-targeting antimicrobial agents zeamines through a zeamine-stimulated RND efflux pump DesABC. Here, we unraveled the mechanism of D. oryzae response to zeamines and determined the distribution and function of this novel ESR in a variety of important plant and human pathogens. Results: In this study, we documented that a two-component system regulator DzrR of D. oryzae EC1 mediates ESR in the presence of envelope-targeting antimicrobial agents. DzrR was found modulating bacterial response and resistance to zeamines through inducing the expression of RND efflux pump DesABC, which is likely independent on DzrR phosphorylation. In addition, DzrR could also mediate bacterial responses to structurally divergent envelope-targeting antimicrobial agents, including chlorhexidine and chlorpromazine. Significantly, the DzrR-mediated response was independent on the five canonical ESRs. We further presented evidence that the DzrR-mediated response is conserved in the bacterial species of Dickeya, Ralstonia, and Burkholderia, showing that a distantly located DzrR homolog is the previously undetermined regulator of RND-8 efflux pump for chlorhexidine resistance in B. cenocepacia. Conclusions: Taken together, the findings from this study depict a new widely distributed Gram-negative ESR mechanism and present a valid target and useful clues to combat antimicrobial resistance.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Liang, Zhibin
Lin, Qiqi
Wang, Qingwei
Huang, Luhao
Liu, Huidi
Shi, Zurong
Cui, Zining
Zhou, Xiaofan
Gao, Yong-Gui
Zhou, Jianuan
Zhang, Lian-Hui
Deng, Yizhen
format Article
author Liang, Zhibin
Lin, Qiqi
Wang, Qingwei
Huang, Luhao
Liu, Huidi
Shi, Zurong
Cui, Zining
Zhou, Xiaofan
Gao, Yong-Gui
Zhou, Jianuan
Zhang, Lian-Hui
Deng, Yizhen
author_sort Liang, Zhibin
title Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response
title_short Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response
title_full Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response
title_fullStr Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response
title_full_unstemmed Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response
title_sort gram-negative bacteria resist antimicrobial agents by a dzrr-mediated envelope stress response
publishDate 2023
url https://hdl.handle.net/10356/169682
_version_ 1773551208656535552
spelling sg-ntu-dr.10356-1696822023-07-31T15:32:14Z Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response Liang, Zhibin Lin, Qiqi Wang, Qingwei Huang, Luhao Liu, Huidi Shi, Zurong Cui, Zining Zhou, Xiaofan Gao, Yong-Gui Zhou, Jianuan Zhang, Lian-Hui Deng, Yizhen School of Biological Sciences NTU Institute of Structural Biology Science::Biological sciences Chlorhexidine Envelope Stress Response Background: Envelope stress responses (ESRs) are critical for adaptive resistance of Gram-negative bacteria to envelope-targeting antimicrobial agents. However, ESRs are poorly defined in a large number of well-known plant and human pathogens. Dickeya oryzae can withstand a high level of self-produced envelope-targeting antimicrobial agents zeamines through a zeamine-stimulated RND efflux pump DesABC. Here, we unraveled the mechanism of D. oryzae response to zeamines and determined the distribution and function of this novel ESR in a variety of important plant and human pathogens. Results: In this study, we documented that a two-component system regulator DzrR of D. oryzae EC1 mediates ESR in the presence of envelope-targeting antimicrobial agents. DzrR was found modulating bacterial response and resistance to zeamines through inducing the expression of RND efflux pump DesABC, which is likely independent on DzrR phosphorylation. In addition, DzrR could also mediate bacterial responses to structurally divergent envelope-targeting antimicrobial agents, including chlorhexidine and chlorpromazine. Significantly, the DzrR-mediated response was independent on the five canonical ESRs. We further presented evidence that the DzrR-mediated response is conserved in the bacterial species of Dickeya, Ralstonia, and Burkholderia, showing that a distantly located DzrR homolog is the previously undetermined regulator of RND-8 efflux pump for chlorhexidine resistance in B. cenocepacia. Conclusions: Taken together, the findings from this study depict a new widely distributed Gram-negative ESR mechanism and present a valid target and useful clues to combat antimicrobial resistance. Published version This study is supported by the National Natural Science Foundation of China (32000085, U22A20480, 32072450, and 31972230), Key Realm R&D Program of Guangdong Province (2018B020205003, 2020B020209001), Guangdong Basic and Applied Basic Research Foundation (2020A1515110465, 2020A1515011534), Guangzhou Science and Technology Plan (201804020066, 202102080488), Guangdong Forestry Science and Technology Innovation Project (2020KJCX009), and Natural Science Foundation of Anhui Province (2108085QC118). 2023-07-31T02:49:58Z 2023-07-31T02:49:58Z 2023 Journal Article Liang, Z., Lin, Q., Wang, Q., Huang, L., Liu, H., Shi, Z., Cui, Z., Zhou, X., Gao, Y., Zhou, J., Zhang, L. & Deng, Y. (2023). Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response. BMC Biology, 21(1), 62-. https://dx.doi.org/10.1186/s12915-023-01565-7 1741-7007 https://hdl.handle.net/10356/169682 10.1186/s12915-023-01565-7 36978084 2-s2.0-85151111941 1 21 62 en BMC Biology © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. application/pdf