| Autor: |
Ghafoori SM; School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, 2650, Australia., Robles AM; Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA, USA., Arada AM; Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA, USA., Shirmast P; School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, 2650, Australia., Dranow DM; Seattle Structural Genomics Center for Infectious Disease, Seattle, WA, USA.; UCB Pharma, Bainbridge Island, WA, USA., Mayclin SJ; Seattle Structural Genomics Center for Infectious Disease, Seattle, WA, USA.; UCB Pharma, Bainbridge Island, WA, USA., Lorimer DD; Seattle Structural Genomics Center for Infectious Disease, Seattle, WA, USA.; UCB Pharma, Bainbridge Island, WA, USA., Myler PJ; Seattle Structural Genomics Center for Infectious Disease, Seattle, WA, USA.; Seattle Children's Research Institute, University of Washington, Seattle, WA, USA., Edwards TE; Seattle Structural Genomics Center for Infectious Disease, Seattle, WA, USA.; UCB Pharma, Bainbridge Island, WA, USA., Kuhn ML; Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA, USA., Forwood JK; School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, 2650, Australia. jforwood@csu.edu.au. |
| Abstrakt: |
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. |
