Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acid
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause recurring bacterial infection in CF patients' lungs. However, the severity of CF lung disease correlates poorly with genotype. Antibiotic treatment helps dramatically prolong patients' life. The lung disease...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2014-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/03683 |
| _version_ | 1811180489648635904 |
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| author | Yajamana Ramu Yanping Xu Hyeon-Gyu Shin Zhe Lu |
| author_facet | Yajamana Ramu Yanping Xu Hyeon-Gyu Shin Zhe Lu |
| author_sort | Yajamana Ramu |
| collection | DOAJ |
| description | Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause recurring bacterial infection in CF patients' lungs. However, the severity of CF lung disease correlates poorly with genotype. Antibiotic treatment helps dramatically prolong patients' life. The lung disease generally determines prognosis and causes most morbidity and mortality; early control of infections is thus critical. Staphylococcus aureus is a main cause of early infection in CF lungs. It secretes sphingomyelinase (SMase) C that can suppress CFTR activity. SMase C also inhibits voltage-gated K+ channels in lymphocytes; inhibition of these channels causes immunosuppression. SMase C's pathogenicity is further illustrated by the demonstration that once Bacillus anthracis is engineered to express high levels of SMase C, the resulting mutant can evade the host immunity elicited by a live vaccine because additional pathogenic mechanisms are created. By screening a chemical library, we find that the natural product tannic acid is an SMase C antidote. |
| first_indexed | 2024-04-11T09:03:59Z |
| format | Article |
| id | doaj.art-9e2369f01f6644cf8de43af53b33d3ca |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:03:59Z |
| publishDate | 2014-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9e2369f01f6644cf8de43af53b33d3ca2022-12-22T04:32:42ZengeLife Sciences Publications LtdeLife2050-084X2014-10-01310.7554/eLife.03683Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acidYajamana Ramu0Yanping Xu1Hyeon-Gyu Shin2Zhe Lu3Department of Physiology, Perelman School of Medicine, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United StatesDepartment of Physiology, Perelman School of Medicine, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United StatesDepartment of Physiology, Perelman School of Medicine, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United StatesDepartment of Physiology, Perelman School of Medicine, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United StatesMutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause recurring bacterial infection in CF patients' lungs. However, the severity of CF lung disease correlates poorly with genotype. Antibiotic treatment helps dramatically prolong patients' life. The lung disease generally determines prognosis and causes most morbidity and mortality; early control of infections is thus critical. Staphylococcus aureus is a main cause of early infection in CF lungs. It secretes sphingomyelinase (SMase) C that can suppress CFTR activity. SMase C also inhibits voltage-gated K+ channels in lymphocytes; inhibition of these channels causes immunosuppression. SMase C's pathogenicity is further illustrated by the demonstration that once Bacillus anthracis is engineered to express high levels of SMase C, the resulting mutant can evade the host immunity elicited by a live vaccine because additional pathogenic mechanisms are created. By screening a chemical library, we find that the natural product tannic acid is an SMase C antidote.https://elifesciences.org/articles/03683potassium channelCFTRphospholipasesphingomyelinasetoxinchannel inhibition |
| spellingShingle | Yajamana Ramu Yanping Xu Hyeon-Gyu Shin Zhe Lu Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acid eLife potassium channel CFTR phospholipase sphingomyelinase toxin channel inhibition |
| title | Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acid |
| title_full | Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acid |
| title_fullStr | Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acid |
| title_full_unstemmed | Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acid |
| title_short | Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acid |
| title_sort | counteracting suppression of cftr and voltage gated k channels by a bacterial pathogenic factor with the natural product tannic acid |
| topic | potassium channel CFTR phospholipase sphingomyelinase toxin channel inhibition |
| url | https://elifesciences.org/articles/03683 |
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