School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, 2650, Australia.
Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA, USA.
Sci Rep. 2021 May 4;11(1):9453. doi: 10.1038/s41598-021-88672-z.
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.
依氏伊丽莎白菌是一种新兴的多药耐药病原体，已在全球引发了多次暴发。依氏伊丽莎白菌属于黄杆菌科大家族，该科包含许多植物、鸟类、鱼类和人类病原体。在依氏伊丽莎白菌基因组中发现了几个抗生素耐药基因，包括氯霉素乙酰转移酶 (CAT)。CAT 在抗生素耐药性中发挥着重要作用，并可在遗传移动元件中转移。它们催化抗生素氯霉素的乙酰化，从而降低其作为治疗有效药物的功效。在这里，我们确定了导致新加坡暴发的依氏伊丽莎白菌 NUHP1 菌株的 CAT 蛋白的高分辨率晶体结构。其结构与经典的 A 型 CAT 不相似，而是与来自铜绿假单胞菌、霍乱弧菌和创伤弧菌的其他先前表征的 B 型 (CatB) 蛋白表现出显著相似性，后者采用六肽重复折叠。此外，依氏伊丽莎白菌的 CAT 蛋白与其他经临床验证的氯霉素耐药基因具有很高的序列相似性，表明它也可能在对抗生素的耐药性中发挥作用。我们的工作扩展了对正在变得越来越成问题的黄杆菌科病原体的蛋白质的有限的结构和功能覆盖范围。
