Virulence and Metabolism Crosstalk: Impaired Activity of the Type Three Secretion System (T3SS) in a <i>Pseudomonas aeruginosa</i> Crc-Defective Mutant
<i>Pseudomonas aeruginosa</i> is a ubiquitous nosocomial opportunistic pathogen that harbors many virulence determinants. Part of <i>P. aeruginosa</i> success colonizing a variety of habitats resides in its metabolic robustness and plasticity, which are the basis of its capab...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| author | Teresa Gil-Gil Trinidad Cuesta Sara Hernando-Amado Jose Antonio Reales-Calderón Fernando Corona Juan F. Linares José L. Martínez |
| author_facet | Teresa Gil-Gil Trinidad Cuesta Sara Hernando-Amado Jose Antonio Reales-Calderón Fernando Corona Juan F. Linares José L. Martínez |
| author_sort | Teresa Gil-Gil |
| collection | DOAJ |
| description | <i>Pseudomonas aeruginosa</i> is a ubiquitous nosocomial opportunistic pathogen that harbors many virulence determinants. Part of <i>P. aeruginosa</i> success colonizing a variety of habitats resides in its metabolic robustness and plasticity, which are the basis of its capability of adaptation to different nutrient sources and ecological conditions, including the infected host. Given this situation, it is conceivable that <i>P. aeruginosa</i> virulence might be, at least in part, under metabolic control, in such a way that virulence determinants are produced just when needed. Indeed, it has been shown that the catabolite repression control protein Crc, which together with the RNA chaperon Hfq regulates the <i>P. aeruginosa</i> utilization of carbon sources at the post-transcriptional level, also regulates, directly or indirectly, virulence-related processes in <i>P. aeruginosa</i>. Among them, Crc regulates <i>P. aeruginosa</i> cytotoxicity, likely by modulating the activity of the Type III Secretion System (T3SS), which directly injects toxins into eukaryotic host cells. The present work shows that the lack of Crc produces a Type III Secretion-defective phenotype in <i>P. aeruginosa</i>. The observed impairment is a consequence of a reduced expression of the genes encoding the T3SS, together with an impaired secretion of the proteins involved. Our results support that the impaired T3SS activity of the <i>crc</i> defective mutant is, at least partly, a consequence of a defective protein export, probably due to a reduced proton motive force. This work provides new information about the complex regulation of the expression and the activity of the T3SS in <i>P. aeruginosa</i>. Our results highlight the need of a robust bacterial metabolism, which is defective in the <i>∆crc</i> mutant, to elicit complex and energetically costly virulence strategies, as that provided by the T3SS. |
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| language | English |
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| publishDate | 2023-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a43cd14795fd459fb84ed7e1c5fab9692023-11-18T23:03:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124151230410.3390/ijms241512304Virulence and Metabolism Crosstalk: Impaired Activity of the Type Three Secretion System (T3SS) in a <i>Pseudomonas aeruginosa</i> Crc-Defective MutantTeresa Gil-Gil0Trinidad Cuesta1Sara Hernando-Amado2Jose Antonio Reales-Calderón3Fernando Corona4Juan F. Linares5José L. Martínez6Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, SpainDepartamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, SpainDepartamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, SpainDepartamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, SpainDepartamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, SpainDepartamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, SpainDepartamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain<i>Pseudomonas aeruginosa</i> is a ubiquitous nosocomial opportunistic pathogen that harbors many virulence determinants. Part of <i>P. aeruginosa</i> success colonizing a variety of habitats resides in its metabolic robustness and plasticity, which are the basis of its capability of adaptation to different nutrient sources and ecological conditions, including the infected host. Given this situation, it is conceivable that <i>P. aeruginosa</i> virulence might be, at least in part, under metabolic control, in such a way that virulence determinants are produced just when needed. Indeed, it has been shown that the catabolite repression control protein Crc, which together with the RNA chaperon Hfq regulates the <i>P. aeruginosa</i> utilization of carbon sources at the post-transcriptional level, also regulates, directly or indirectly, virulence-related processes in <i>P. aeruginosa</i>. Among them, Crc regulates <i>P. aeruginosa</i> cytotoxicity, likely by modulating the activity of the Type III Secretion System (T3SS), which directly injects toxins into eukaryotic host cells. The present work shows that the lack of Crc produces a Type III Secretion-defective phenotype in <i>P. aeruginosa</i>. The observed impairment is a consequence of a reduced expression of the genes encoding the T3SS, together with an impaired secretion of the proteins involved. Our results support that the impaired T3SS activity of the <i>crc</i> defective mutant is, at least partly, a consequence of a defective protein export, probably due to a reduced proton motive force. This work provides new information about the complex regulation of the expression and the activity of the T3SS in <i>P. aeruginosa</i>. Our results highlight the need of a robust bacterial metabolism, which is defective in the <i>∆crc</i> mutant, to elicit complex and energetically costly virulence strategies, as that provided by the T3SS.https://www.mdpi.com/1422-0067/24/15/12304type III secretion<i>Pseudomonas aeruginosa</i>Crccatabolic repressionmetabolism-virulence crosstalkproton motive force |
| spellingShingle | Teresa Gil-Gil Trinidad Cuesta Sara Hernando-Amado Jose Antonio Reales-Calderón Fernando Corona Juan F. Linares José L. Martínez Virulence and Metabolism Crosstalk: Impaired Activity of the Type Three Secretion System (T3SS) in a <i>Pseudomonas aeruginosa</i> Crc-Defective Mutant International Journal of Molecular Sciences type III secretion <i>Pseudomonas aeruginosa</i> Crc catabolic repression metabolism-virulence crosstalk proton motive force |
| title | Virulence and Metabolism Crosstalk: Impaired Activity of the Type Three Secretion System (T3SS) in a <i>Pseudomonas aeruginosa</i> Crc-Defective Mutant |
| title_full | Virulence and Metabolism Crosstalk: Impaired Activity of the Type Three Secretion System (T3SS) in a <i>Pseudomonas aeruginosa</i> Crc-Defective Mutant |
| title_fullStr | Virulence and Metabolism Crosstalk: Impaired Activity of the Type Three Secretion System (T3SS) in a <i>Pseudomonas aeruginosa</i> Crc-Defective Mutant |
| title_full_unstemmed | Virulence and Metabolism Crosstalk: Impaired Activity of the Type Three Secretion System (T3SS) in a <i>Pseudomonas aeruginosa</i> Crc-Defective Mutant |
| title_short | Virulence and Metabolism Crosstalk: Impaired Activity of the Type Three Secretion System (T3SS) in a <i>Pseudomonas aeruginosa</i> Crc-Defective Mutant |
| title_sort | virulence and metabolism crosstalk impaired activity of the type three secretion system t3ss in a i pseudomonas aeruginosa i crc defective mutant |
| topic | type III secretion <i>Pseudomonas aeruginosa</i> Crc catabolic repression metabolism-virulence crosstalk proton motive force |
| url | https://www.mdpi.com/1422-0067/24/15/12304 |
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