Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading threat to public health as it is resistant to most currently available antibiotics. Prodigiosin is a secondary metabolite of microorganisms with broad-spectrum antibacterial activity. This study identified a significant antibacterial ef...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-01-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1333526/full |
| _version_ | 1797349401802309632 |
|---|---|
| author | Xiaoxia Liu Zonglin Wang Zonglin Wang Zhongyu You Wei Wang Yujie Wang Wenjing Wu Yongjia Peng Suping Zhang Yinan Yun Jin Zhang |
| author_facet | Xiaoxia Liu Zonglin Wang Zonglin Wang Zhongyu You Wei Wang Yujie Wang Wenjing Wu Yongjia Peng Suping Zhang Yinan Yun Jin Zhang |
| author_sort | Xiaoxia Liu |
| collection | DOAJ |
| description | Methicillin-resistant Staphylococcus aureus (MRSA) is a leading threat to public health as it is resistant to most currently available antibiotics. Prodigiosin is a secondary metabolite of microorganisms with broad-spectrum antibacterial activity. This study identified a significant antibacterial effect of prodigiosin against MRSA with a minimum inhibitory concentration as low as 2.5 mg/L. The results of scanning electron microscopy, crystal violet staining, and confocal laser scanning microscopy indicated that prodigiosin inhibited biofilm formation in S. aureus USA300, while also destroying the structure of the cell wall and cell membrane, which was confirmed by transmission electron microscopy. At a prodigiosin concentration of 1.25 mg/L, biofilm formation was inhibited by 76.24%, while 2.5 mg/L prodigiosin significantly reduced the vitality of MRSA cells in the biofilm. Furthermore, the transcriptomic results obtained at 1/8 MIC of prodigiosin indicated that 235and 387 genes of S. aureus USA300 were significantly up- and downregulated, respectively. The downregulated genes were related to two-component systems, including the transcriptional regulator LytS, quorum sensing histidine kinases SrrB, NreA and NreB, peptidoglycan biosynthesis enzymes (MurQ and GlmU), iron-sulfur cluster repair protein ScdA, microbial surface components recognizing adaptive matrix molecules, as well as the key arginine synthesis enzymes ArcC and ArgF. The upregulated genes were mainly related to cell wall biosynthesis, as well as two-component systems including vancomycin resistance-associated regulator, lipoteichoic acid biosynthesis related proteins DltD and DltB, as well as the 9 capsular polysaccharide biosynthesis proteins. This study elucidated the molecular mechanisms through which prodigiosin affects the cell envelope of MRSA from the perspectives of cell wall synthesis, cell membrane and biofilm formation, providing new potential targets for the development of antimicrobials for the treatment of MRSA. |
| first_indexed | 2024-03-08T12:29:23Z |
| format | Article |
| id | doaj.art-8dea091a195c4aa5bbc3847ac1124dab |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-08T12:29:23Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-8dea091a195c4aa5bbc3847ac1124dab2024-01-22T04:46:32ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-01-011510.3389/fmicb.2024.13335261333526Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureusXiaoxia Liu0Zonglin Wang1Zonglin Wang2Zhongyu You3Wei Wang4Yujie Wang5Wenjing Wu6Yongjia Peng7Suping Zhang8Yinan Yun9Jin Zhang10College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, ChinaCollege of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, ChinaCollege of Geography and Environmental Sciences, Zhejiang Normal University, Jinhua, ChinaCollege of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, ChinaClinical Laboratory of First Hospital of Jiaxing, Jiaxing, ChinaCollege of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, ChinaCollege of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, ChinaCollege of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, ChinaCollege of Advanced Materials Engineering, Jiaxing Nanhu University, Jiaxing, ChinaCollege of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, ChinaCollege of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, ChinaMethicillin-resistant Staphylococcus aureus (MRSA) is a leading threat to public health as it is resistant to most currently available antibiotics. Prodigiosin is a secondary metabolite of microorganisms with broad-spectrum antibacterial activity. This study identified a significant antibacterial effect of prodigiosin against MRSA with a minimum inhibitory concentration as low as 2.5 mg/L. The results of scanning electron microscopy, crystal violet staining, and confocal laser scanning microscopy indicated that prodigiosin inhibited biofilm formation in S. aureus USA300, while also destroying the structure of the cell wall and cell membrane, which was confirmed by transmission electron microscopy. At a prodigiosin concentration of 1.25 mg/L, biofilm formation was inhibited by 76.24%, while 2.5 mg/L prodigiosin significantly reduced the vitality of MRSA cells in the biofilm. Furthermore, the transcriptomic results obtained at 1/8 MIC of prodigiosin indicated that 235and 387 genes of S. aureus USA300 were significantly up- and downregulated, respectively. The downregulated genes were related to two-component systems, including the transcriptional regulator LytS, quorum sensing histidine kinases SrrB, NreA and NreB, peptidoglycan biosynthesis enzymes (MurQ and GlmU), iron-sulfur cluster repair protein ScdA, microbial surface components recognizing adaptive matrix molecules, as well as the key arginine synthesis enzymes ArcC and ArgF. The upregulated genes were mainly related to cell wall biosynthesis, as well as two-component systems including vancomycin resistance-associated regulator, lipoteichoic acid biosynthesis related proteins DltD and DltB, as well as the 9 capsular polysaccharide biosynthesis proteins. This study elucidated the molecular mechanisms through which prodigiosin affects the cell envelope of MRSA from the perspectives of cell wall synthesis, cell membrane and biofilm formation, providing new potential targets for the development of antimicrobials for the treatment of MRSA.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1333526/fullprodigiosinmethicillin-resistant Staphylococcus aureusbiofilmtranscriptomic analysismolecular mechanism |
| spellingShingle | Xiaoxia Liu Zonglin Wang Zonglin Wang Zhongyu You Wei Wang Yujie Wang Wenjing Wu Yongjia Peng Suping Zhang Yinan Yun Jin Zhang Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus Frontiers in Microbiology prodigiosin methicillin-resistant Staphylococcus aureus biofilm transcriptomic analysis molecular mechanism |
| title | Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus |
| title_full | Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus |
| title_fullStr | Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus |
| title_full_unstemmed | Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus |
| title_short | Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus |
| title_sort | transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin resistant staphylococcus aureus |
| topic | prodigiosin methicillin-resistant Staphylococcus aureus biofilm transcriptomic analysis molecular mechanism |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1333526/full |
| work_keys_str_mv | AT xiaoxialiu transcriptomicanalysisofcellenvelopeinhibitionbyprodigiosininmethicillinresistantstaphylococcusaureus AT zonglinwang transcriptomicanalysisofcellenvelopeinhibitionbyprodigiosininmethicillinresistantstaphylococcusaureus AT zonglinwang transcriptomicanalysisofcellenvelopeinhibitionbyprodigiosininmethicillinresistantstaphylococcusaureus AT zhongyuyou transcriptomicanalysisofcellenvelopeinhibitionbyprodigiosininmethicillinresistantstaphylococcusaureus AT weiwang transcriptomicanalysisofcellenvelopeinhibitionbyprodigiosininmethicillinresistantstaphylococcusaureus AT yujiewang transcriptomicanalysisofcellenvelopeinhibitionbyprodigiosininmethicillinresistantstaphylococcusaureus AT wenjingwu transcriptomicanalysisofcellenvelopeinhibitionbyprodigiosininmethicillinresistantstaphylococcusaureus AT yongjiapeng transcriptomicanalysisofcellenvelopeinhibitionbyprodigiosininmethicillinresistantstaphylococcusaureus AT supingzhang transcriptomicanalysisofcellenvelopeinhibitionbyprodigiosininmethicillinresistantstaphylococcusaureus AT yinanyun transcriptomicanalysisofcellenvelopeinhibitionbyprodigiosininmethicillinresistantstaphylococcusaureus AT jinzhang transcriptomicanalysisofcellenvelopeinhibitionbyprodigiosininmethicillinresistantstaphylococcusaureus |