Bacterial resistance evolution by recruitment of super-integron gene cassettes

被引:165
作者
Rowe-Magnus, DA [1 ]
Guerout, AM [1 ]
Mazel, D [1 ]
机构
[1] Inst Pasteur, Dept Biotechnol, CNRS, URA 1444,Unite Programmat Mol & Toxicol Genet, F-75724 Paris, France
关键词
D O I
10.1046/j.1365-2958.2002.02861.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The capture and spread of antibiotic resistance determinants by integrons underlies the rapid evolution of multiple antibiotic resistance among diverse Gram-negative clinical isolates. The association of multiple resistance integrons (MRIs) with mobile DNA elements facilitates their transit across phylogenetic boundaries and augments the potential impact of integrons on bacterial evolution. Recently, ancestral chromosomal versions, the super-integrons (Sis), were found to be genuine components of the genomes of diverse bacterial species. SIs possess evolutionary characteristics and stockpiles of adaptive functions, including cassettes related to antibiotic resistance determinants previously characterized in clinical isolates, which suggest that MRIs and their resistance genes were originally recruited from Sis and their pool of amassed genes. However, the recombination activity of integrons has never been demonstrated in a bacterium other than Escherichia coli We introduced a naturally occurring MRI (Tp(R), Sul(R)) on a conjugative plasmid into Vibrio, cholerae, a species known to harbour a SI. We show that MRIs can randomly recruit genes directly from the cache of SI cassettes. By applying a selective constraint for the development of antibiotic resistance, we demonstrate bacterial resistance evolution through the recruitment a novel, but phenotypically silent, chloramphenicol acetyltransferase gene from the V cholerae SI and its precise insertion into the MRI. The resulting resistance profile (Cm-R, Tp(R), Sul(R)) could then be disseminated by conjugation to other clinically relevant pathogens at high frequency. These results demonstrate that otherwise phenotypically sensitive strains may still be a genetic source for the evolution of resistance to clinically relevant antibiotics through integron-mediated recombination events.
引用
收藏
页码:1657 / 1669
页数:13
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