Novel Insight into the Effects of CpxR on <i>Salmonella enteritidis</i> Cells during the Chlorhexidine Treatment and Non-Stressful Growing Conditions
The development and spread of antibiotics and biocides resistance is a significant global challenge. To find a solution for this emerging problem, the discovery of novel bacterial cellular targets and the critical pathways associated with antimicrobial resistance is needed. In the present study, we...
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8938 |
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| author | Xiaoying Liu Misara Omar Kakambi V. Nagaraja Sagar M. Goyal Sinisa Vidovic |
| author_facet | Xiaoying Liu Misara Omar Kakambi V. Nagaraja Sagar M. Goyal Sinisa Vidovic |
| author_sort | Xiaoying Liu |
| collection | DOAJ |
| description | The development and spread of antibiotics and biocides resistance is a significant global challenge. To find a solution for this emerging problem, the discovery of novel bacterial cellular targets and the critical pathways associated with antimicrobial resistance is needed. In the present study, we investigated the role of the two most critical envelope stress response regulators, RpoE and CpxR, on the physiology and susceptibility of growing <i>Salmonella</i> <i>enterica</i> serovar <i>enteritidis</i> cells using the polycationic antimicrobial agent, chlorhexidine (CHX). It was shown that deletion of the <i>cpxR</i> gene significantly increased the susceptibility of this organism, whereas deletion of the <i>rpoE</i> gene had no effect on the pathogen’s susceptibility to this antiseptic. It has been shown that a lack of the CpxR regulator induces multifaceted stress responses not only in the envelope but also in the cytosol, further affecting the key biomolecules, including DNA, RNA, and proteins. We showed that alterations in cellular trafficking and most of the stress responses are associated with a dysfunctional CpxR regulator during exponential growth phase, indicating that these physiological changes are intrinsically associated with the lack of the CpxR regulator. In contrast, induction of type II toxin-antitoxin systems and decrease of abundances of enzymes and proteins associated with the recycling of muropeptides and resistance to polymixin and cationic antimicrobial peptides were specific responses of the ∆<i>cpxR</i> mutant to the CHX treatment. Overall, our study provides insight into the effects of CpxR on the physiology of <i>S</i>. Enteritidis cells during the exponential growth phase and CHX treatment, which may point to potential cellular targets for the development of an effective antimicrobial agent. |
| first_indexed | 2024-03-10T08:44:18Z |
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| language | English |
| last_indexed | 2024-03-10T08:44:18Z |
| publishDate | 2021-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c7a74f8103184336a20085636a80f1082023-11-22T08:02:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216893810.3390/ijms22168938Novel Insight into the Effects of CpxR on <i>Salmonella enteritidis</i> Cells during the Chlorhexidine Treatment and Non-Stressful Growing ConditionsXiaoying Liu0Misara Omar1Kakambi V. Nagaraja2Sagar M. Goyal3Sinisa Vidovic4Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55108, USADepartment of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55108, USADepartment of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55108, USAVeterinary Diagnostic Laboratory, Department of Veterinary Population Medicine, University of Minnesota, Saint Paul, MN 55108, USAFood Safety and Preservation Team, The New Zealand Institute for Plant and Food Research Limited, Auckland 1025, New ZealandThe development and spread of antibiotics and biocides resistance is a significant global challenge. To find a solution for this emerging problem, the discovery of novel bacterial cellular targets and the critical pathways associated with antimicrobial resistance is needed. In the present study, we investigated the role of the two most critical envelope stress response regulators, RpoE and CpxR, on the physiology and susceptibility of growing <i>Salmonella</i> <i>enterica</i> serovar <i>enteritidis</i> cells using the polycationic antimicrobial agent, chlorhexidine (CHX). It was shown that deletion of the <i>cpxR</i> gene significantly increased the susceptibility of this organism, whereas deletion of the <i>rpoE</i> gene had no effect on the pathogen’s susceptibility to this antiseptic. It has been shown that a lack of the CpxR regulator induces multifaceted stress responses not only in the envelope but also in the cytosol, further affecting the key biomolecules, including DNA, RNA, and proteins. We showed that alterations in cellular trafficking and most of the stress responses are associated with a dysfunctional CpxR regulator during exponential growth phase, indicating that these physiological changes are intrinsically associated with the lack of the CpxR regulator. In contrast, induction of type II toxin-antitoxin systems and decrease of abundances of enzymes and proteins associated with the recycling of muropeptides and resistance to polymixin and cationic antimicrobial peptides were specific responses of the ∆<i>cpxR</i> mutant to the CHX treatment. Overall, our study provides insight into the effects of CpxR on the physiology of <i>S</i>. Enteritidis cells during the exponential growth phase and CHX treatment, which may point to potential cellular targets for the development of an effective antimicrobial agent.https://www.mdpi.com/1422-0067/22/16/8938<i>Salmonella</i>CpxR regulatorchlorhexidineantimicrobial resistanceproteomics |
| spellingShingle | Xiaoying Liu Misara Omar Kakambi V. Nagaraja Sagar M. Goyal Sinisa Vidovic Novel Insight into the Effects of CpxR on <i>Salmonella enteritidis</i> Cells during the Chlorhexidine Treatment and Non-Stressful Growing Conditions International Journal of Molecular Sciences <i>Salmonella</i> CpxR regulator chlorhexidine antimicrobial resistance proteomics |
| title | Novel Insight into the Effects of CpxR on <i>Salmonella enteritidis</i> Cells during the Chlorhexidine Treatment and Non-Stressful Growing Conditions |
| title_full | Novel Insight into the Effects of CpxR on <i>Salmonella enteritidis</i> Cells during the Chlorhexidine Treatment and Non-Stressful Growing Conditions |
| title_fullStr | Novel Insight into the Effects of CpxR on <i>Salmonella enteritidis</i> Cells during the Chlorhexidine Treatment and Non-Stressful Growing Conditions |
| title_full_unstemmed | Novel Insight into the Effects of CpxR on <i>Salmonella enteritidis</i> Cells during the Chlorhexidine Treatment and Non-Stressful Growing Conditions |
| title_short | Novel Insight into the Effects of CpxR on <i>Salmonella enteritidis</i> Cells during the Chlorhexidine Treatment and Non-Stressful Growing Conditions |
| title_sort | novel insight into the effects of cpxr on i salmonella enteritidis i cells during the chlorhexidine treatment and non stressful growing conditions |
| topic | <i>Salmonella</i> CpxR regulator chlorhexidine antimicrobial resistance proteomics |
| url | https://www.mdpi.com/1422-0067/22/16/8938 |
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