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.

Details

Title
Structural characterization of a Type B chloramphenicol acetyltransferase from the emerging pathogen Elizabethkingia anophelis NUHP1
Author
Ghafoori, Seyed Mohammad 1 ; Robles, Alyssa M 2 ; Arada, Angelika M 2 ; Paniz, Shirmast 1 ; Dranow, David M 3 ; Mayclin, Stephen J 3 ; Lorimer, Donald D 3 ; Myler, Peter J 4 ; Edwards, Thomas E 3 ; Kuhn, Misty L 2 ; Forwood, Jade K 1 

 Charles Sturt University, School of Biomedical Sciences, Wagga Wagga, Australia (GRID:grid.1037.5) (ISNI:0000 0004 0368 0777) 
 San Francisco State University, Department of Chemistry and Biochemistry, San Francisco, USA (GRID:grid.263091.f) (ISNI:0000000106792318) 
 Seattle Structural Genomics Center for Infectious Disease, Seattle, USA (GRID:grid.53964.3d) (ISNI:0000 0004 0463 2611); UCB Pharma, Bainbridge Island, USA (GRID:grid.432688.3) 
 Seattle Structural Genomics Center for Infectious Disease, Seattle, USA (GRID:grid.53964.3d) (ISNI:0000 0004 0463 2611); University of Washington, Seattle Children’s Research Institute, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2521814621
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.