Molecular structure and translocation of a multiple antibiotic resistance region of aPsychrobacter psychrophiluspermafrost strain

Abstract

A Psychrobacter psychrophilus strain resistant to tetracycline and streptomycin was isolated from a 15,000-35,000-year-old permafrost subsoil sediment sampled from the coast of the Eastern-Siberian Sea. The genes conferring antibiotic resistance were localized on an c. 30-kb pKLH80 plasmid. It was shown that the antibiotic resistance region of this plasmid has a mosaic structure and contains closely linked streptomycin resistance (strA-strB) and tetracycline resistance [tetR-tet(H)] genes, followed by a novel IS element (ISPpy1) belonging to the IS3 family. Both the strA-strB and tetR-tet(H) genes of pKLH80 were highly similar to those found in modern clinical bacterial isolates. It was shown that the ISPpy1 element of pKLH80 can direct translocation of the adjacent antibiotic resistance genes to different target plasmids, either by one-ended transposition or by formation of a composite transposon resulting from the insertion of the ISPpy1 second copy at the other side of the antibiotic resistance region. Thus, our data demonstrate that clinically important antibiotic resistance genes originated long before the introduction of antibiotics into clinical practice and confirm an important role of horizontal gene transfer in the distribution of these genes in natural bacterial populations.

Genotypic-Phenotypic Discrepancies between Antibiotic Resistance Characteristics of Escherichia coli Isolates from Calves in Management Settings with High and Low Antibiotic Use

“…The gene pair strA-strB is widespread in bacteria associated with plants, humans, and animals, including bacteria from Ͼ15,000-year-old permafrost sediments (41,44). When strA and strB are cloned separately, strB is not expressed because of a secondary structure barrier to the Shine-Dalgarno sequence and start codon (10), a finding consistent with our observations that nonsynonymous changes in strA also affect the phenotype caused by strB.…”

Genetic structure and biological properties of the first ancient multiresistance plasmid pKLH80 isolated from a permafrost bacterium

“…Together they form the plasmid backbone region. The accessory region of the pKLH80 plasmid contains five antibiotic resistance genes: previously characterized genes, strA-strB and tetRtet(H) (Petrova et al, 2009), and an additional gene discovered in this work, bla RTG . Two IS elements, ISAba14 and ISPsma1, were also found in this region, in addition to ISPpy1 identified previously (Petrova et al, 2009(Petrova et al, , 2013.…”

The Prehistory of Antibiotic Resistance

“…Detailed analysis of the vancomycin resistance gene cluster in this metagenome revealed conservation of gene sequence and synteny with modern resistance clusters in the clinic as well as protein function and structure. Other studies have shown the presence of resistance genes in Siberian permafrost (Petrova et al 2009) and showed working resistance genes from at least 5000 years ago using functional metagenomics (Perron et al 2015). Isolated instances of resistance genes in human commensals and pathogens have also been documented.…”