Abstract
Clear similarities between antibiotic resistance islands in the chromosomes of extensively antibiotic-resistant isolates from the two dominant, globally distributed Acinetobacter baumannii clones, GC1 and GC2, suggest a common origin. A close relative of the likely progenitor of both of these regions was found in R1215, a conjugative IncM plasmid from a Serratia marcescens strain isolated prior to 1980. The 37.8-kb resistance region in R1215 lies within the mucB gene and includes aacC1, aadA1, aphA1b, bla TEM, catA1, sul1, and tetA(A), genes that confer resistance to gentamicin, streptomycin and spectinomycin, kanamycin and neomycin, ampicillin, chloramphenicol, sulfamethoxazole, and tetracycline, respectively. The backbone of this region is derived from Tn1721 and is interrupted by a hybrid Tn2670 (Tn21)-Tn1696-type transposon, Tn6020, and an incomplete Tn1. After minor rearrangements, this R1215 resistance island can generate AbGRI2-0*, the predicted earliest form of the IS26-bounded AbGRI2-type resistance island of GC2 isolates, and to the multiple antibiotic resistance region (MARR) of AbaR0, the precursor of this region in AbaR-type resistance islands in the GC1 group. A 29.9-kb circle excised by IS26 has been inserted into the A.baumannii chromosome to generate AbGRI2-0*. To create the MARR of AbaR0, a different circular form, again generated by IS26 from an R1215 resistance region variant, has been opened at a different point by recombination with a copy of the sul1 gene already present in the AbaR precursor. Recent IncM plasmids related to R1215 have a variant resistance island containing a bla SHV gene in the same location. IMPORTANCE Two lineages of extensively antibiotic-resistant A.baumannii currently plaguing modern medicine each acquired resistance to all of the original antibiotics (ampicillin, tetracycline, kanamycin, and sulfonamides) by the end of the 1970s and then became resistant to antibiotics from newer families after they were introduced in the 1980s. Here, we show that, in both of the dominant globally disseminated A.baumannii clones, a related set of antibiotic resistance genes was acquired together from the same resistance region that had already evolved in an IncM plasmid. In both cases, the action of IS26 was important in this process, but homologous recombination was also involved. The findings highlight the fact that complex regions carrying several resistance genes can evolve in one location or organism and all or part of the evolved region can then move to other locations and other organisms, conferring resistance to several antibiotics in a single step.
Highlights
Clear similarities between antibiotic resistance islands in the chromosomes of extensively antibiotic-resistant isolates from the two dominant, globally distributed Acinetobacter baumannii clones, GC1 and GC2, suggest a common origin
The class 1 integron in SGI1 genomic islands found in Salmonella and Proteus chromosomes has many internal configurations, many A/C plasmids carry a form of the ARI-A resistance island [7], which has a fixed location but varied gene content, and evolution of a resistance region in situ has been reported for IncHI1 plasmids [9] and IncL/M plasmids [10]
A group of 16 Escherichia coli strains containing plasmids of known incompatibility type obtained from the United Kingdom National Collection of Type Cultures (NCTC) for use as references for PCR-based replicon typing was screened for resistance phenotype and, using PCR, for resistance and other genes as described elsewhere [22]
Summary
Clear similarities between antibiotic resistance islands in the chromosomes of extensively antibiotic-resistant isolates from the two dominant, globally distributed Acinetobacter baumannii clones, GC1 and GC2, suggest a common origin. Gram-negative bacteria share a relatively small number of genes that confer resistance to the original antibiotics (such as ampicillin, tetracycline, kanamycin, and sulfonamides) These genes have all been shown to be included within mobile elements that facilitate their spread, namely, compound or class I transposons, class II transposons, or class 1 integrons and their associated gene cassettes. Acinetobacter baumannii is an important nosocomial pathogen whose treatment is increasingly problematic due to high levels of antibiotic resistance Both globally disseminated clones, global clones 1 and 2 (GC1 and GC2), contain several antibiotic resistance genes in chromosomally located resistance islands that are made up of transposons and fragments of transposons. The R1215 resistance island was compared to both the AbaR MARR and AbGRI2
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