Structural characterization of a Type B chloramphenicol acetyltransferase from the emerging pathogen Elizabethkingia anophelis NUHP1
Abstract Elizabethkingia anophelis is an emerging multidrug resistant pathogen that has caused several global outbreaks. E. anophelis belongs to the large family of Flavobacteriaceae, which contains many bacteria that are plant, bird, fish, and human pathogens. Several antibiotic resistance genes ar...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-88672-z |
| _version_ | 1818754072578097152 |
|---|---|
| author | Seyed Mohammad Ghafoori Alyssa M. Robles Angelika M. Arada Paniz Shirmast David M. Dranow Stephen J. Mayclin Donald D. Lorimer Peter J. Myler Thomas E. Edwards Misty L. Kuhn Jade K. Forwood |
| author_facet | Seyed Mohammad Ghafoori Alyssa M. Robles Angelika M. Arada Paniz Shirmast David M. Dranow Stephen J. Mayclin Donald D. Lorimer Peter J. Myler Thomas E. Edwards Misty L. Kuhn Jade K. Forwood |
| author_sort | Seyed Mohammad Ghafoori |
| collection | DOAJ |
| description | Abstract Elizabethkingia anophelis is an emerging multidrug resistant pathogen that has caused several global outbreaks. E. anophelis belongs to the large family of Flavobacteriaceae, which contains many bacteria that are plant, bird, fish, and human pathogens. Several antibiotic resistance genes are found within the E. anophelis genome, including a chloramphenicol acetyltransferase (CAT). CATs play important roles in antibiotic resistance and can be transferred in genetic mobile elements. They catalyse the acetylation of the antibiotic chloramphenicol, thereby reducing its effectiveness as a viable drug for therapy. Here, we determined the high-resolution crystal structure of a CAT protein from the E. anophelis NUHP1 strain that caused a Singaporean outbreak. Its structure does not resemble that of the classical Type A CATs but rather exhibits significant similarity to other previously characterized Type B (CatB) proteins from Pseudomonas aeruginosa, Vibrio cholerae and Vibrio vulnificus, which adopt a hexapeptide repeat fold. Moreover, the CAT protein from E. anophelis displayed high sequence similarity to other clinically validated chloramphenicol resistance genes, indicating it may also play a role in resistance to this antibiotic. Our work expands the very limited structural and functional coverage of proteins from Flavobacteriaceae pathogens which are becoming increasingly more problematic. |
| first_indexed | 2024-12-18T05:17:26Z |
| format | Article |
| id | doaj.art-2d0fc8d578e94f488773d631f30cf36a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T05:17:26Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2d0fc8d578e94f488773d631f30cf36a2022-12-21T21:19:44ZengNature PortfolioScientific Reports2045-23222021-05-0111111010.1038/s41598-021-88672-zStructural characterization of a Type B chloramphenicol acetyltransferase from the emerging pathogen Elizabethkingia anophelis NUHP1Seyed Mohammad Ghafoori0Alyssa M. Robles1Angelika M. Arada2Paniz Shirmast3David M. Dranow4Stephen J. Mayclin5Donald D. Lorimer6Peter J. Myler7Thomas E. Edwards8Misty L. Kuhn9Jade K. Forwood10School of Biomedical Sciences, Charles Sturt UniversityDepartment of Chemistry and Biochemistry, San Francisco State UniversityDepartment of Chemistry and Biochemistry, San Francisco State UniversitySchool of Biomedical Sciences, Charles Sturt UniversitySeattle Structural Genomics Center for Infectious DiseaseSeattle Structural Genomics Center for Infectious DiseaseSeattle Structural Genomics Center for Infectious DiseaseSeattle Structural Genomics Center for Infectious DiseaseSeattle Structural Genomics Center for Infectious DiseaseDepartment of Chemistry and Biochemistry, San Francisco State UniversitySchool of Biomedical Sciences, Charles Sturt UniversityAbstract Elizabethkingia anophelis is an emerging multidrug resistant pathogen that has caused several global outbreaks. E. anophelis belongs to the large family of Flavobacteriaceae, which contains many bacteria that are plant, bird, fish, and human pathogens. Several antibiotic resistance genes are found within the E. anophelis genome, including a chloramphenicol acetyltransferase (CAT). CATs play important roles in antibiotic resistance and can be transferred in genetic mobile elements. They catalyse the acetylation of the antibiotic chloramphenicol, thereby reducing its effectiveness as a viable drug for therapy. Here, we determined the high-resolution crystal structure of a CAT protein from the E. anophelis NUHP1 strain that caused a Singaporean outbreak. Its structure does not resemble that of the classical Type A CATs but rather exhibits significant similarity to other previously characterized Type B (CatB) proteins from Pseudomonas aeruginosa, Vibrio cholerae and Vibrio vulnificus, which adopt a hexapeptide repeat fold. Moreover, the CAT protein from E. anophelis displayed high sequence similarity to other clinically validated chloramphenicol resistance genes, indicating it may also play a role in resistance to this antibiotic. Our work expands the very limited structural and functional coverage of proteins from Flavobacteriaceae pathogens which are becoming increasingly more problematic.https://doi.org/10.1038/s41598-021-88672-z |
| spellingShingle | Seyed Mohammad Ghafoori Alyssa M. Robles Angelika M. Arada Paniz Shirmast David M. Dranow Stephen J. Mayclin Donald D. Lorimer Peter J. Myler Thomas E. Edwards Misty L. Kuhn Jade K. Forwood Structural characterization of a Type B chloramphenicol acetyltransferase from the emerging pathogen Elizabethkingia anophelis NUHP1 Scientific Reports |
| title | Structural characterization of a Type B chloramphenicol acetyltransferase from the emerging pathogen Elizabethkingia anophelis NUHP1 |
| title_full | Structural characterization of a Type B chloramphenicol acetyltransferase from the emerging pathogen Elizabethkingia anophelis NUHP1 |
| title_fullStr | Structural characterization of a Type B chloramphenicol acetyltransferase from the emerging pathogen Elizabethkingia anophelis NUHP1 |
| title_full_unstemmed | Structural characterization of a Type B chloramphenicol acetyltransferase from the emerging pathogen Elizabethkingia anophelis NUHP1 |
| title_short | Structural characterization of a Type B chloramphenicol acetyltransferase from the emerging pathogen Elizabethkingia anophelis NUHP1 |
| title_sort | structural characterization of a type b chloramphenicol acetyltransferase from the emerging pathogen elizabethkingia anophelis nuhp1 |
| url | https://doi.org/10.1038/s41598-021-88672-z |
| work_keys_str_mv | AT seyedmohammadghafoori structuralcharacterizationofatypebchloramphenicolacetyltransferasefromtheemergingpathogenelizabethkingiaanophelisnuhp1 AT alyssamrobles structuralcharacterizationofatypebchloramphenicolacetyltransferasefromtheemergingpathogenelizabethkingiaanophelisnuhp1 AT angelikamarada structuralcharacterizationofatypebchloramphenicolacetyltransferasefromtheemergingpathogenelizabethkingiaanophelisnuhp1 AT panizshirmast structuralcharacterizationofatypebchloramphenicolacetyltransferasefromtheemergingpathogenelizabethkingiaanophelisnuhp1 AT davidmdranow structuralcharacterizationofatypebchloramphenicolacetyltransferasefromtheemergingpathogenelizabethkingiaanophelisnuhp1 AT stephenjmayclin structuralcharacterizationofatypebchloramphenicolacetyltransferasefromtheemergingpathogenelizabethkingiaanophelisnuhp1 AT donalddlorimer structuralcharacterizationofatypebchloramphenicolacetyltransferasefromtheemergingpathogenelizabethkingiaanophelisnuhp1 AT peterjmyler structuralcharacterizationofatypebchloramphenicolacetyltransferasefromtheemergingpathogenelizabethkingiaanophelisnuhp1 AT thomaseedwards structuralcharacterizationofatypebchloramphenicolacetyltransferasefromtheemergingpathogenelizabethkingiaanophelisnuhp1 AT mistylkuhn structuralcharacterizationofatypebchloramphenicolacetyltransferasefromtheemergingpathogenelizabethkingiaanophelisnuhp1 AT jadekforwood structuralcharacterizationofatypebchloramphenicolacetyltransferasefromtheemergingpathogenelizabethkingiaanophelisnuhp1 |