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.
Highlights
Flavobacteriaceae is a large family of Gram-negative, mostly aerobic bacteria found in a wide variety of environments[1]
integrative conjugative element (ICE) is a mobile genetic element that integrates into the host chromosome, replicates, excises, and forms a plasmid in order to be transferred to other bacterial cells via horizontal conjugation
NUHP1 harbors, we determined the structure of the protein encoded by the catB gene using X-ray crystallography (Table 1)
Summary
Flavobacteriaceae is a large family of Gram-negative, mostly aerobic bacteria found in a wide variety of environments[1]. Elizabethkingia is an opportunistic, emerging pathogen that has caused recent outbreaks among the general population and immunocompromised patients in Asia and North America, in Singapore, Hong Kong, Taiwan, and the United States (Wisconsin, Illinois and Michigan)[10,11] It was first isolated in 1949 from infants with septicemia or meningitis and was initially classified under the genus Flavobacterium[12]. Since the E. anophelis NUHP1 strain has caused significant outbreaks in recent years, the Seattle Center for Structural Genomics of Infectious Diseases selected antibiotic resistance proteins from this pathogen for structural determination. One of these proteins is CatB, which is predicted to be a chloramphenicol acetyltransferase. Since the E. anophelis catB gene is conserved across all Elizabethkingia strains and CatB proteins are critical for Cm resistance in important
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