Abstract
BackgroundGram-negative multidrug-resistant (MDR) bacteria are major causes of nosocomial infections, and antibiotic resistance in these organisms is often plasmid mediated. Data are scarce pertaining to molecular mechanisms of antibiotic resistance in resource constrained areas such as Iraq.Methodology/Principal FindingsIn this study, all MDR Enterobacteriaceae (n = 38) and randomly selected non-MDR counterparts (n = 41) isolated from patients, healthcare workers and environmental surfaces in a newly opened hospital in Iraq were investigated to characterize plasmids found in these isolates and determine their contribution to antibiotic resistance. Our results demonstrated that MDR E. coli and K. pneumoniae isolates harbored significantly more (≥3) plasmids compared to their non-MDR counterparts, which carried ≤2 plasmids (p<0.01). Various large plasmids (∼52 to 100 kb) from representative isolates were confirmed to contain multiple resistance genes by DNA microarray analysis. Aminoglycoside (acc, aadA, aph, strA/B, and ksgA), β-lactam (bla TEM1, bla AMPC, bla CTX-M-15, bla OXA-1, bla VIM-2 and bla SHV), sulfamethoxazole/trimethoprim (sul/dfr), tetracycline (tet) and chloramphenicol (cat) resistance genes were detected on these plasmids. Additionally, multiple plasmids carrying multiple antibiotic resistance genes were found in the same host strain. Genetic transfer-associated genes were identified on the plasmids from both MDR and non-MDR isolates. Seven plasmid replicon types (FII, FIA, FIB, B/O, K, I1 and N) were detected in the isolates, while globally disseminated IncA/C and IncHI1 plasmids were not detected in these isolates.Conclusions/SignificanceThis is the first report of the characteristics of the plasmids found in Enterobacteriaceae isolated following the opening of a new hospital in Iraq. The information provided here furthers our understanding of the mechanisms of drug resistance in this specific region and their evolutionary relationship with other parts of world. The large plasmids, carrying resistance genes and transfer-associated genes, may be potential factors for regional dissemination of antibiotic resistance.
Highlights
Antibiotic resistance in bacterial pathogens is steadily increasing and recognized as one of the greatest threats to global public health [1]
In Gram-negative bacteria, genes such as blaSHV, blaTEM, blaCTX and blaAMPC presented in E. coli, K. pneumoniae and Acinetobacter spp. encode extended-spectrum blactamases (ESBLs) that are often located on plasmids [5]
We focused on the impact of the plasmids on drug resistance and the genetic features of the plasmids harbored in these multidrug resistant bacteria
Summary
Antibiotic resistance in bacterial pathogens is steadily increasing and recognized as one of the greatest threats to global public health [1]. The genetic features of the drug resistance in Gram-negative Enterobacteriaceae from certain geographic locations such as Iraq have not been defined due to constrained resources. There are several factors responsible for dissemination of antimicrobial resistance genes among bacterial strains, and plasmid-mediated transfer has been considered one of the most important mechanisms for the horizontal transfer of multidrug resistance [2,3,4]. In Gram-negative bacteria, genes such as blaSHV, blaTEM, blaCTX and blaAMPC presented in E. coli, K. pneumoniae and Acinetobacter spp. encode extended-spectrum blactamases (ESBLs) that are often located on plasmids [5]. The genes found in many Gram-negative bacilli including Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. encode class A, B and D b-lactamases that mediate resistance to various b-lactam antibiotics have been found on plasmids [6,7,8].
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