The importance of integrons for development and propagation of resistance in Shigella: the case of Latin America

Abstract In Latin America, the disease burden of shigellosis is found to coexist with the rapid and rampant spread of resistance to commonly used antibiotics. The molecular basis of antibiotic resistance lies within genetic elements such as plasmids, transposons, integrons, genomic islands, etc., which are found in the bacterial genome. Integrons are known to acquire, exchange, and express genes within gene cassettes and it is hypothesized that they play a significant role in the transmission of multidrug resistance genes in several Gram-negative bacteria including Shigella. A few studies have described antibiotic resistance genes and integrons among multidrug resistant Shigella isolates found in Latin America. For example, in Brazil, Bolivia, Chile, Costa Rica and Peru, class 1 and class 2 integrons have been detected among multidrug resistant strains of Shigella; this phenomenon is more frequently observed in S. flexneri isolates that are resistant to trimethoprim, sulfamethoxazole, streptomycin, ampicillin, chloramphenicol, and tetracycline. The gene cassette sul2, which is frequently detected in Shigella strains resistant to the sulfonamides, suggests that the sulfonamide-resistant phenotype can be explained by the presence of the sul2 genes independent of the integron class detected. It is to be noted that sul3 was negative in all isolates analyzed in these studies.The high frequency of sulfonamide (as encoded by sul2) and trimethoprim resistance is likely to be a result of the recurrent use of trimethoprim sulfamethoxazole as a popular regimen for the treatment of shigellosis. The observed resistance profiles of Shigella strains confirm that ampicillin and trimethoprim-sulfamethoxazole are ineffective as therapeutic options. In-depth information regarding antibiotic resistance mechanism in this pathogen is needed in order to develop suitable intervention strategies. There is a pressing need for regional and local antimicrobial resistance profiling of Shigella to be included as a part of the public health strategy.

Molecular Detection of Antimicrobial Resistance Gene Cassettes Associated with Class 2 Integron in Salmonella Serovars Isolated in Iran.

Aim: Salmonella is an important food-borne pathogen in humans and a broad range of animals. Antimicrobial resistance in Salmonella spp. is a serious health problem in human and veterinary medicine worldwide. The aim of this study was to detect integrons, the natural recombination systems that can be transferred in companion with mobile genetic elements and play a major role in spreading antibiotic resistance genes in clinical isolates. Place and Duration of Study: Salmonella clinical isolates were provided by a number of institutes and hospitals over the country through the years 2008-2009. Methodology: Antimicrobial susceptibility testing and serotyping were carried out for eighty four epidemiologically unrelated clinical isolates of Salmonella serovars collected from different provinces of Iran through the years 2008-2009. PCR assays were carried out to detect intI2 gene (integrase I attributed to class 2 integron) and internal variable regions (IVRs) of class 2 integron. These sequences were deposited in EMBL/GenBank database (www.ncbi.nlm.nih.gov). Results: Eleven isolates (13.1%) which were resistant to at least 4 groups of antimicrobial agents were considered as MDR (multidrug resistant) Salmonella serovars. PCR assays detected intI2 gene (integrase I attributed to class 2 integron) and internal variable regions (IVRs) of class 2 integron in Fourteen (16.7%) and eleven (78.6%) of Salmonella clinical isolates respectively. Analysis of the sequence data revealed 3 gene cassette arrays deposited in Genbank databases including the dhfrA1 (0.75 kb), dfrA14- lsp (1 kb), dhfrA1- sat2-aadA1 (3 kb) with three IVR distribution patterns. An artifact PCR product of 2 kb was reported in this study to be amplified together with IVRs of class 2 integrons which was associated with the fhuE- ptsG genes. Conclusions: Presence of MDR Salmonella serovars demonstrates that antimicrobial selection pressure is widespread in our clinical settings. Detection of class 2 integron carrying gene cassettes which confer resistance to different classes of antibiotics such as aminoglycosides, and trimethoprim confirms that integron-mediated antimicrobial gene cassettes are prevalent in Salmonella serovars isolated in Iran.

Study on Integron of AmpC Enzyme-producing Escherichia Coli / 中国药房

OBJECTIVE:To investigate the classification,structure and integron-mediated AmpC enzyme gene transfer of integron in 25 strains of AmpC enzymeproducing Escherichia coli. METHODS:Sensitivity of test strains to 20 kinds of antibiotics was tested by microdilution method. PCR and sequencing were performed on test strains to identify integrase gene(intI)and its location,the product of variable region of positive integrons(Int)respectively. RESULTS:Class ⅠintI were indentified in 20 strains (80%)of 25 strains Escherichia coli. The most drug resistance box cassettes were aadA5 and dfr17 and integory encoding AmpC gene cassette was not observed. CONCLUSION:Class Ⅰ integron resided in AmpC enzyme-producing Escherichia coli widely. The cause of drug resistance of integorn to aminoglycosides,sulfonamides,chloramphenicol is drug resistance gene cassette. Gene cassette does not play important role in integron-mediated antibiotic resistant gene transformation.

Study on Integron in 59 Strains of Escherichia Coli / 中国药房

OBJECTIVE: To investigate the classification, structure and inducing drug resistance of integron in 59 strains of cefoxitin-resistant Escherichia coli. METHODS: PCR method was used to detect integrase gene (intI) and product of variable region of positive strain was performed on sequencing. Sensitiveness of experimental strains to 22 kinds of antibiotics was detected with microdilution method. RESULTS: IntI1 was identified in 45 strains (76%) of the 59 strains Escherichia coli. The most drug resistance genes cassettes were aadA5 and dfr17,only 2 strains encoding ?-lactamase drug resistance gene cassettes. The MIC of integron positive groups was statistically significantly higher than negative groups. CONCLUSION: Class 1 integron resided in cefoxitin-resistant Escherichia coli widely. The cause of drug resistance of integron positive strain to aminoglycosides, sulfonamides and chloramphenicol is drug resistance gene cassettes. Gene cassettes does not play important role in integron-mediated drug resistance.