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 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.

Epidemiology and Characteristics of Elizabethkingia spp. Infections in Southeast Asia

“…; Table S2: Potential virulence-associated features among Elizabethkingia spp. as predicted using the Virulence Factor Database (VFDB) [ 39 , 40 , 41 , 43 , 44 , 46 , 59 , 60 , 61 , 62 , 72 , 73 , 77 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 ].…”

Chloramphenicol Binding Sites of Acinetobacter baumannii Chloramphenicol Acetyltransferase CatB8

“…Previous studies have shown that in Cats, residues Y30, S32, and H79 are located at the active site and can form hydrophilic contacts with chl. 21,25 In CatB8, R51 has the potential to establish a hydrogen bond with chl: 3, while residues N20 and D41 may participate in interactions with chl: 4, Q77 may interact with chl: 1 and 2, and E94 can interact with chl: 3 (Figure 4).…”

“…Chl has antibiofilm properties and can effectively kill various bacteria and prevent colony growth. 25,33 However, owing to the severe side effects of chl, it has not been the first choice for treating internal bacterial infection. Instead, it is more widely used for topical treatment or some ocular infections.…”

“…baumannii is one of the main pathogens responsible for nosocomial infections. , Its resistance to surface disinfection and multidrug resistance make it easy to spread between patients and difficult to treat. Chl has antibiofilm properties and can effectively kill various bacteria and prevent colony growth. , However, owing to the severe side effects of chl, it has not been the first choice for treating internal bacterial infection. Instead, it is more widely used for topical treatment or some ocular infections .…”

Draft Genome Sequences of Nine Stenotrophomonas maltophilia Isolates from a Freshwater Catchment Area in Hong Kong

“…All isolates carry the L1 metallo-β-lactamase, as well as sul4 ( 24 ). ACYCe.8N also carries sul2 , katG ( 25 ), and catB11 ( 26 – 28 ).…”