Perfis genômicos do transposon Tn4401 de isolados de Proteus sp., Providencia sp. e Morganella sp

Abstract

Antibiotic resistance is a growing global threat to public health, causing high mortality. Mutation, genetic drift, horizontal gene transfer via transposons, and natural selection are the basic mechanisms responsible for the spread of resistance genes among bacterial populations. The Proteeae tribe is composed of three genera: Proteus spp., Morganella spp. and Providencia spp., opportunistic pathogenic bacteria that are resistant to [beta]-lactams. The highly mobile transposon Tn4401 from Klebsiella pneumoniae and Escherichia coli is characterized by containing blaKPC genes encoding [beta]-lactamase, ensuring resistance to β-lactams. The objective was to analyze the evolutionary history of the genomes of the Proteeae tribe and its Tn4401 transposons, through patterns, variations and syntenies of genome sequences and their neighboring regions. Initially, the sequences of K. pneumoniae Tn4401 (Kp15, Kp512, Kp529-1) were used as a query in BLASTn/NCBI to search for strains of the Proteeae tribe. Then the selected GenBank files were used in Islandviewer 4.0 software for similarity and synteny analysis and the FASTAS sequences were incorporated into ClustalW/MEGA 11. After alignment, the ratio non-synonymous for synonymous substitutions was established. Different isoforms of Tn4401 were revealed, between them Tn4401a, Tn4401b and Tn4401d containing blaKPC. Several patterns of gene sitenia of transposon were detected, involving deletions, inversions, duplications and mobility of neighboring gene groups, sometimes similar, sometimes different. Purifying selection was an active force in the β-lactamases of the analyzed strains. We also detected a possible relationship between the transposon isoforms and neighboring islands of resistance to Mercury, Chromate and Sulfonamide. These findings emphasize the continuous action of different evolutionary processes on plasmids and on the Tn4401 element, as well as the possible potential for dissemination of resistance genes by the Proteeae tribe.