Complex Multiple Antibiotic and Mercury Resistance Region Derived from the r-det of NR1 (R100)

Abstract

The sequence of the 45.2-kb multidrug and mercury resistance region of pRMH760, a large plasmid from a clinical isolate of Klebsiella pneumoniae collected in 1997 in Australia, was completed. Most of the modules found in the resistance determinant (r-det), or Tn2670, region of NR1 (also known as R100), isolated from a Shigella flexneri strain in Japan in the late 1950s, were present in pRMH760 but in a different configuration. The location was also different, with the Tn2670-derived region flanked by the transposition module of Tn1696 and a mercury resistance module almost identical to one found in the plasmid pDU1358. This arrangement is consistent with a three-step process. First, the r-det was circularized via homologous recombination between the IS1 elements and reincorporated at a new location, possibly in a different plasmid, via homologous recombination between the 5-conserved (5-CS) or 3-CS of the In34 integron in the r-det and the same region of a second class 1 integron in a Tn1696 relative. Subsequently, resolvase-mediated recombination between the res sites in the r-det and a second mercury resistance transposon removed one end of the Tn1696-like transposon and part of the second transposon. Other events occurring within the r-det-derived portion have also contributed to the formation of the pRMH760 resistance region. Tn2 or a close relative that includes the bla TEM-1b gene had moved into the Tn21 mercury resistance module with subsequent deletion of the adjacent sequence, and all four 38-bp inverted repeats corresponding to Tn21 family transposon termini have been interrupted by an IS4321-like element.

Urinary Tract Infections in a South American Population: Dynamic Spread of Class 1 Integrons and Multidrug Resistance by Homologous and Site-Specific Recombination

“…In this instance, we would assume that the 5293 hybrid arose by a resolution event between transposons Tn21 and Tn5051, which were located in the same replicon. Such an event has a precedent, perhaps the most notable being the possible role of this process in the evolution of some bla TEM-1 -containing transposons (32), but also includes the transposon backbone in which In34 is located (31). The hybrid observed here is noteworthy insomuch as Tn5051-like transposons are commonly associated with environmental bacteria (27).…”

“…In contrast, the transposon backbone beyond IRt, the mer module, is identical to Tn21 itself. The hybrid backbone seen here is analogous to the context of In34, an integron with an In2-like integron structure and a member of the broader In5-like family of integrons (31,33). The structure carrying In34 is presumed to have been generated by homologous recombination since, while it has a Tn21 mer region at its IRt end, it possesses a Tn5036-like tnp region at the IRi integron end with an insertion point at this latter end identical to that seen in Tn1696 (In4).…”

A Class 1 Integron Present in a Human Commensal Has a Hybrid Transposition Module Compared to Tn 402 : Evidence of Interaction with Mobile DNA from Natural Environments

“…It is likely, therefore, that the mediating event was site specific and involved TniR-mediated resolution of the two parents located in the same replicon. Such an event has previously been suggested for evolution of some bla TEM -containing transposons (36) and for evolution of a transposon in pRMH760 (35). Based on the information available, we concluded only that Tn6007 is a hybrid compared to Tn402.…”

Tn 6060 , a Transposon from a Genomic Island in a Pseudomonas aeruginosa Clinical Isolate That Includes Two Class 1 Integrons

“…Where multiple arrays are present, biases in conventional PCR may preclude detectable amplification of larger arrays at the expense of smaller ones. Also, the point has been made previously (11,15) that a variety of genetic elements and processes contribute to the spread of resistance and that detailed examination of the context in which such elements as integrons are located can be particularly insightful in comparing and understanding multidrug-resistant isolates (7,13). More systematic and detailed sequence analyses may therefore shed light on the mechanisms by which integrons and their arrays move through pathogens.…”

“…In addition, this integron, while comprising a defective transposition module, lacks the insertion elements normally associated with the In4 family (including In28) or In5 family of class 1 integrons (10,12,15). Beyond the IRt inverted repeat is a 547-bp region identical to sequence within the urf2 gene, which is part of the Tn21-like mercury resistance transposons (11). The sequence abuts the IRi end of a second class 1 integron with a different, smaller cassette array, aacC3-cmlA5.…”