Testing a Human Antimicrobial RNase Chimera Against Bacterial Resistance
The emergence of bacterial resistance to the most commonly used antibiotics encourages the design of novel antimicrobial drugs. Antimicrobial proteins and peptides (AMPs) are the key players in host innate immunity. They exert a rapid and multifaceted action that reduces the development of bacterial...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.01357/full |
| _version_ | 1818134794251272192 |
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| author | Guillem Prats-Ejarque Jiarui Li Fatima Ait-Ichou Helena Lorente Ester Boix |
| author_facet | Guillem Prats-Ejarque Jiarui Li Fatima Ait-Ichou Helena Lorente Ester Boix |
| author_sort | Guillem Prats-Ejarque |
| collection | DOAJ |
| description | The emergence of bacterial resistance to the most commonly used antibiotics encourages the design of novel antimicrobial drugs. Antimicrobial proteins and peptides (AMPs) are the key players in host innate immunity. They exert a rapid and multifaceted action that reduces the development of bacterial adaptation mechanisms. Human antimicrobial RNases belonging to the vertebrate specific RNase A superfamily participate in the maintenance of tissue and body fluid sterility. Among the eight human canonical RNases, RNase 3 stands out as the most cationic and effective bactericidal protein against Gram-negative species. Its enhanced ability to disrupt the bacterial cell wall has evolved in detriment of its catalytic activity. Based on structure-functional studies we have designed an RNase 3/1 hybrid construct that combines the high catalytic activity of RNase 1 with RNase 3 bactericidal properties. Next, we have explored the ability of this hybrid RNase to target the development of bacterial resistance on an Acinetobacter baumannii cell culture. Synergy assays were performed in combination with colistin, a standard antimicrobial peptide used as an antibiotic to treat severe infections. Positive synergism was observed between colistin and the RNase 3/1 hybrid protein. Subsequently, using an in vitro experimental evolution assay, by exposure of a bacterial culture to colistin at incremental doses, we demonstrated the ability of the RNase 3/1 construct to reduce the emergence of bacterial antimicrobial resistance. The results advance the potential applicability of RNase-based drugs as antibiotic adjuvants. |
| first_indexed | 2024-12-11T09:14:17Z |
| format | Article |
| id | doaj.art-0a2a7b1b24bf44b18c3d44c9473793da |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-11T09:14:17Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-0a2a7b1b24bf44b18c3d44c9473793da2022-12-22T01:13:25ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-06-011010.3389/fmicb.2019.01357439768Testing a Human Antimicrobial RNase Chimera Against Bacterial ResistanceGuillem Prats-EjarqueJiarui LiFatima Ait-IchouHelena LorenteEster BoixThe emergence of bacterial resistance to the most commonly used antibiotics encourages the design of novel antimicrobial drugs. Antimicrobial proteins and peptides (AMPs) are the key players in host innate immunity. They exert a rapid and multifaceted action that reduces the development of bacterial adaptation mechanisms. Human antimicrobial RNases belonging to the vertebrate specific RNase A superfamily participate in the maintenance of tissue and body fluid sterility. Among the eight human canonical RNases, RNase 3 stands out as the most cationic and effective bactericidal protein against Gram-negative species. Its enhanced ability to disrupt the bacterial cell wall has evolved in detriment of its catalytic activity. Based on structure-functional studies we have designed an RNase 3/1 hybrid construct that combines the high catalytic activity of RNase 1 with RNase 3 bactericidal properties. Next, we have explored the ability of this hybrid RNase to target the development of bacterial resistance on an Acinetobacter baumannii cell culture. Synergy assays were performed in combination with colistin, a standard antimicrobial peptide used as an antibiotic to treat severe infections. Positive synergism was observed between colistin and the RNase 3/1 hybrid protein. Subsequently, using an in vitro experimental evolution assay, by exposure of a bacterial culture to colistin at incremental doses, we demonstrated the ability of the RNase 3/1 construct to reduce the emergence of bacterial antimicrobial resistance. The results advance the potential applicability of RNase-based drugs as antibiotic adjuvants.https://www.frontiersin.org/article/10.3389/fmicb.2019.01357/fullRNaseantimicrobial resistanceantibiotic adjuvantgram-negative bacteriaantimicrobial peptides |
| spellingShingle | Guillem Prats-Ejarque Jiarui Li Fatima Ait-Ichou Helena Lorente Ester Boix Testing a Human Antimicrobial RNase Chimera Against Bacterial Resistance Frontiers in Microbiology RNase antimicrobial resistance antibiotic adjuvant gram-negative bacteria antimicrobial peptides |
| title | Testing a Human Antimicrobial RNase Chimera Against Bacterial Resistance |
| title_full | Testing a Human Antimicrobial RNase Chimera Against Bacterial Resistance |
| title_fullStr | Testing a Human Antimicrobial RNase Chimera Against Bacterial Resistance |
| title_full_unstemmed | Testing a Human Antimicrobial RNase Chimera Against Bacterial Resistance |
| title_short | Testing a Human Antimicrobial RNase Chimera Against Bacterial Resistance |
| title_sort | testing a human antimicrobial rnase chimera against bacterial resistance |
| topic | RNase antimicrobial resistance antibiotic adjuvant gram-negative bacteria antimicrobial peptides |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.01357/full |
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