Nisin Z Potential for the Control of Diabetic Foot Infections Promoted by <i>Pseudomonas aeruginosa</i> Persisters
Diabetic foot ulcers (DFU) are a major complication of diabetes mellitus and a public health concern worldwide. The ability of <i>P. aeruginosa</i> to form biofilms is a key factor responsible for the chronicity of diabetic foot infections (DFIs) and frequently associated with the presen...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/12/5/794 |
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| author | Rafaela Zina Eva Cunha Isa Serrano Elisabete Silva Luís Tavares Manuela Oliveira |
| author_facet | Rafaela Zina Eva Cunha Isa Serrano Elisabete Silva Luís Tavares Manuela Oliveira |
| author_sort | Rafaela Zina |
| collection | DOAJ |
| description | Diabetic foot ulcers (DFU) are a major complication of diabetes mellitus and a public health concern worldwide. The ability of <i>P. aeruginosa</i> to form biofilms is a key factor responsible for the chronicity of diabetic foot infections (DFIs) and frequently associated with the presence of persister cells. These are a subpopulation of phenotypic variants highly tolerant to antibiotics for which new therapeutic alternatives are urgently needed, such as those based on antimicrobial peptides. This study aimed to evaluate the inhibitory effect of nisin Z on <i>P. aeruginosa</i> DFI persisters. To induce the development of a persister state in both planktonic suspensions and biofilms, <i>P. aeruginosa</i> DFI isolates were exposed to carbonyl cyanide m-chlorophenylhydrazone (CCCP) and ciprofloxacin, respectively. After RNA extraction from CCCP-induced persisters, transcriptome analysis was performed to evaluate the differential gene expression between the control, persisters, and persister cells exposed to nisin Z. Nisin Z presented a high inhibitory effect against <i>P. aeruginosa</i> persister cells but was unable to eradicate them when present in established biofilms. Transcriptome analysis revealed that persistence was associated with downregulation of genes related to metabolic processes, cell wall synthesis, and dysregulation of stress response and biofilm formation. After nisin Z treatment, some of the transcriptomic changes induced by persistence were reversed. In conclusion, nisin Z could be considered as a potential complementary therapy for treating <i>P. aeruginosa</i> DFI, but it should be applied as an early treatment or after wound debridement. |
| first_indexed | 2024-03-11T04:00:42Z |
| format | Article |
| id | doaj.art-82af718fa88d443985ad086685f963ab |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-11T04:00:42Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-82af718fa88d443985ad086685f963ab2023-11-18T00:11:18ZengMDPI AGAntibiotics2079-63822023-04-0112579410.3390/antibiotics12050794Nisin Z Potential for the Control of Diabetic Foot Infections Promoted by <i>Pseudomonas aeruginosa</i> PersistersRafaela Zina0Eva Cunha1Isa Serrano2Elisabete Silva3Luís Tavares4Manuela Oliveira5CIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, 1300-477 Lisboa, PortugalCIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, 1300-477 Lisboa, PortugalCIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, 1300-477 Lisboa, PortugalCIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, 1300-477 Lisboa, PortugalCIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, 1300-477 Lisboa, PortugalCIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, 1300-477 Lisboa, PortugalDiabetic foot ulcers (DFU) are a major complication of diabetes mellitus and a public health concern worldwide. The ability of <i>P. aeruginosa</i> to form biofilms is a key factor responsible for the chronicity of diabetic foot infections (DFIs) and frequently associated with the presence of persister cells. These are a subpopulation of phenotypic variants highly tolerant to antibiotics for which new therapeutic alternatives are urgently needed, such as those based on antimicrobial peptides. This study aimed to evaluate the inhibitory effect of nisin Z on <i>P. aeruginosa</i> DFI persisters. To induce the development of a persister state in both planktonic suspensions and biofilms, <i>P. aeruginosa</i> DFI isolates were exposed to carbonyl cyanide m-chlorophenylhydrazone (CCCP) and ciprofloxacin, respectively. After RNA extraction from CCCP-induced persisters, transcriptome analysis was performed to evaluate the differential gene expression between the control, persisters, and persister cells exposed to nisin Z. Nisin Z presented a high inhibitory effect against <i>P. aeruginosa</i> persister cells but was unable to eradicate them when present in established biofilms. Transcriptome analysis revealed that persistence was associated with downregulation of genes related to metabolic processes, cell wall synthesis, and dysregulation of stress response and biofilm formation. After nisin Z treatment, some of the transcriptomic changes induced by persistence were reversed. In conclusion, nisin Z could be considered as a potential complementary therapy for treating <i>P. aeruginosa</i> DFI, but it should be applied as an early treatment or after wound debridement.https://www.mdpi.com/2079-6382/12/5/794diabetic foot infectionnisin Zpersister cells<i>Pseudomonas aeruginosa</i>transcriptome |
| spellingShingle | Rafaela Zina Eva Cunha Isa Serrano Elisabete Silva Luís Tavares Manuela Oliveira Nisin Z Potential for the Control of Diabetic Foot Infections Promoted by <i>Pseudomonas aeruginosa</i> Persisters Antibiotics diabetic foot infection nisin Z persister cells <i>Pseudomonas aeruginosa</i> transcriptome |
| title | Nisin Z Potential for the Control of Diabetic Foot Infections Promoted by <i>Pseudomonas aeruginosa</i> Persisters |
| title_full | Nisin Z Potential for the Control of Diabetic Foot Infections Promoted by <i>Pseudomonas aeruginosa</i> Persisters |
| title_fullStr | Nisin Z Potential for the Control of Diabetic Foot Infections Promoted by <i>Pseudomonas aeruginosa</i> Persisters |
| title_full_unstemmed | Nisin Z Potential for the Control of Diabetic Foot Infections Promoted by <i>Pseudomonas aeruginosa</i> Persisters |
| title_short | Nisin Z Potential for the Control of Diabetic Foot Infections Promoted by <i>Pseudomonas aeruginosa</i> Persisters |
| title_sort | nisin z potential for the control of diabetic foot infections promoted by i pseudomonas aeruginosa i persisters |
| topic | diabetic foot infection nisin Z persister cells <i>Pseudomonas aeruginosa</i> transcriptome |
| url | https://www.mdpi.com/2079-6382/12/5/794 |
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