Doxycycline induces Hok toxin killing in host E. coli.
The antibacterial efficacy of the tetracycline antibiotics has been greatly reduced by the development of resistance, hence a decline in their clinical use. The hok/sok locus is a type I toxin/antitoxin plasmid stability element, often associated with multi-drug resistance plasmids, especially ESBL-...
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0235633&type=printable |
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| author | Chinwe Uzoma Chukwudi Liam Good |
| author_facet | Chinwe Uzoma Chukwudi Liam Good |
| author_sort | Chinwe Uzoma Chukwudi |
| collection | DOAJ |
| description | The antibacterial efficacy of the tetracycline antibiotics has been greatly reduced by the development of resistance, hence a decline in their clinical use. The hok/sok locus is a type I toxin/antitoxin plasmid stability element, often associated with multi-drug resistance plasmids, especially ESBL-encoding plasmids. It enhances host cell survivability and pathogenicity in stressful growth conditions, and increases bacterial tolerance to β-lactam antibiotics. The hok/sok locus forms dsRNA by RNA:RNA interactions between the toxin encoding mRNA and antitoxin non-coding RNA, and doxycycline has been reported to bind dsRNA structures and inhibit their cleavage/processing by the dsRNase, RNase III. This study investigated the antibacterial activities of doxycycline in hok/sok host bacteria cells, the effects on hok/sok-induced changes in growth and the mechanism(s) involved. Diverse strains of E. coli were transformed with hok/sok plasmids and assessed for doxycycline susceptibility and growth changes. The results show that the hok/sok locus increases bacterial susceptibility to doxycycline, which is more apparent in strains with more pronounced hok/sok-induced growth effects. The increased doxycycline susceptibility occurs despite β-lactam resistance imparted by hok/sok. Doxycycline was found to induce bacterial death in a manner phenotypically characteristic of Hok toxin expression, suggesting that it inhibits the toxin/antitoxin dsRNA degradation, leading to Hok toxin expression and cell death. In this way, doxycycline could counteract the multi-drug resistance plasmid maintenance/propagation, persistence and pathogenicity mechanisms associated with the hok/sok locus, which could potentially help in efforts to mitigate the rise of antimicrobial resistance. |
| format | Article |
| id | doaj-art-1cebc798f6414a03bdb88de13fa0f581 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-1cebc798f6414a03bdb88de13fa0f5812025-08-20T02:17:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01157e023563310.1371/journal.pone.0235633Doxycycline induces Hok toxin killing in host E. coli.Chinwe Uzoma ChukwudiLiam GoodThe antibacterial efficacy of the tetracycline antibiotics has been greatly reduced by the development of resistance, hence a decline in their clinical use. The hok/sok locus is a type I toxin/antitoxin plasmid stability element, often associated with multi-drug resistance plasmids, especially ESBL-encoding plasmids. It enhances host cell survivability and pathogenicity in stressful growth conditions, and increases bacterial tolerance to β-lactam antibiotics. The hok/sok locus forms dsRNA by RNA:RNA interactions between the toxin encoding mRNA and antitoxin non-coding RNA, and doxycycline has been reported to bind dsRNA structures and inhibit their cleavage/processing by the dsRNase, RNase III. This study investigated the antibacterial activities of doxycycline in hok/sok host bacteria cells, the effects on hok/sok-induced changes in growth and the mechanism(s) involved. Diverse strains of E. coli were transformed with hok/sok plasmids and assessed for doxycycline susceptibility and growth changes. The results show that the hok/sok locus increases bacterial susceptibility to doxycycline, which is more apparent in strains with more pronounced hok/sok-induced growth effects. The increased doxycycline susceptibility occurs despite β-lactam resistance imparted by hok/sok. Doxycycline was found to induce bacterial death in a manner phenotypically characteristic of Hok toxin expression, suggesting that it inhibits the toxin/antitoxin dsRNA degradation, leading to Hok toxin expression and cell death. In this way, doxycycline could counteract the multi-drug resistance plasmid maintenance/propagation, persistence and pathogenicity mechanisms associated with the hok/sok locus, which could potentially help in efforts to mitigate the rise of antimicrobial resistance.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0235633&type=printable |
| spellingShingle | Chinwe Uzoma Chukwudi Liam Good Doxycycline induces Hok toxin killing in host E. coli. PLoS ONE |
| title | Doxycycline induces Hok toxin killing in host E. coli. |
| title_full | Doxycycline induces Hok toxin killing in host E. coli. |
| title_fullStr | Doxycycline induces Hok toxin killing in host E. coli. |
| title_full_unstemmed | Doxycycline induces Hok toxin killing in host E. coli. |
| title_short | Doxycycline induces Hok toxin killing in host E. coli. |
| title_sort | doxycycline induces hok toxin killing in host e coli |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0235633&type=printable |
| work_keys_str_mv | AT chinweuzomachukwudi doxycyclineinduceshoktoxinkillinginhostecoli AT liamgood doxycyclineinduceshoktoxinkillinginhostecoli |