The Relationship Between Class I and II Integrons and Antibiotic Resistance Among Escherichia coli Isolates From Urinary Tract Infections

© 2018 The Author(s); Published by Alborz University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. Background Urinary tract infection (UTI) is one of the major bacterial infections among patients. Although E. coli is present in gut flora,1 it can cause infection under some conditions as an opportunistic strain, when it spreads from gastrointestinal site. E. coli isolates are responsible for more than 80% of UTIs, but are more likely to cause infection in women.2 Likewise, they cause infections in lower respiratory tract, skin, soft tissues, bloodstream, several other diseases such as pneumonia, and also lower rate of endocarditis, bacteremia, arthritis, and bone inflammation. Eye infections in the ICU wards have also been reported.3 E. coli also leads to wound and surgical site infections. The development of antibiotic resistance by uropathogenic E. coli (UPEC) has led to severe problems in the treatment of infections.4,5 The uptake of genetic elements such as plasmids, integrons and transposons by E. coli is a key factor in the dissemination of drug-resistance.6 Integrons which are transmitted horizontally include several genetic factors which can carry and spread drug resistance among these bacteria. These elements are one of the major approaches for spread of these genes among multi-drug resistant (MDR) strains. More than 9 classes of integrons have been detected, among which class I integron is the predominant class among both gram-positive and gramnegative species.7 According to the reports, approximately 70 various resistance genes are inserted into integrons which cause resistance to beta lactams, aminoglycosides, sulfonamides, macrolides and chloramphenicol which have been reported among E. coli and other species.8 The aims of this study were determination of antibiotic resistance and investigation of the prevalence of class I and II integrons in UPEC.


Background
Urinary tract infection (UTI) is one of the major bacterial infections among patients.Although E. coli is present in gut flora, 1 it can cause infection under some conditions as an opportunistic strain, when it spreads from gastrointestinal site.E. coli isolates are responsible for more than 80% of UTIs, but are more likely to cause infection in women. 2 Likewise, they cause infections in lower respiratory tract, skin, soft tissues, bloodstream, several other diseases such as pneumonia, and also lower rate of endocarditis, bacteremia, arthritis, and bone inflammation.Eye infections in the ICU wards have also been reported. 3E. coli also leads to wound and surgical site infections.The development of antibiotic resistance by uropathogenic E. coli (UPEC) has led to severe problems in the treatment of infections. 4,5he uptake of genetic elements such as plasmids, integrons and transposons by E. coli is a key factor in the dissemination of drug-resistance. 6Integrons which are transmitted horizontally include several genetic factors which can carry and spread drug resistance among these bacteria.These elements are one of the major approaches for spread of these genes among multi-drug resistant (MDR) strains.More than 9 classes of integrons have been detected, among which class I integron is the predominant class among both gram-positive and gramnegative species. 7According to the reports, approximately 70 various resistance genes are inserted into integrons which cause resistance to beta lactams, aminoglycosides, sulfonamides, macrolides and chloramphenicol which have been reported among E. coli and other species. 8he aims of this study were determination of antibiotic resistance and investigation of the prevalence of class I and II integrons in UPEC.

Detection of Integrons by Polymerase Chain Reaction
Polymerase chain reaction (PCR) with specific primers (listed in Table 1) was used to detect the class 1 and class 2 integrons among UPEC.

Results
Sixty-three percent of E. coli isolates were collected from females and 37% from the male patients.Most of isolates were resistant to the amoxicillin (72%), erythromycin (70%), ciprofloxacin (66%), nalidixic acid (57%), and tetracycline (55%).In addition, the highest sensitivity was observed to the nitrofurantoin disc among the isolates.The resistance pattern of isolates has been depicted in Figure 1.
The class I and II integrons were detected in 32% (26 female and 6 male patients) and 21% (18 female and 3 male patients) of isolates, respectively.There were significant relationships between resistance to trimethoprimsulfamethoxazole (P < 0.001), ciprofloxacin (P < 0.01), and tetracycline (P < 0.005), and the class I integron.The class I integron gene was highly detected in the UPEC, possibly playing a role in the dissemination of drug resistance.

Discussion
In the present survey, among 100 E. coli isolates from UTIs, the prevalence of infection was higher in the females compared to the male patients.The majority of isolates were resistant to amoxicillin (72%), followed by erythromycin (69%), ciprofloxacin, ceftazidime, nalidixic acid, and tetracycline; while most of them indicated sensitivity to trimethoprim-sulfamethoxazole, norfloxacin, chloramphenicol, gentamicin, imipenem, amikacin, and nitrofurantoin (99%).
The results of previous studies have demonstrated a higher percentage of resistance [10][11][12] ; and likewise, the rate of nalidixic acid resistance was significant supposing the existence of the NA-encoding gene, integrated into the integron classes. 13esistance to the third and fourth generation cephalosporins and carbapenems has spread worldwide and in the country level and therefore has caused concerns.The role of inter-hospital or patient-to-patient transmission of resistance genes, especially those carried by integrons must be controlled and considered with surveillance programs.
Escherichia coli isolates mostly carried class I integrons (31%) as was reported in other studies; thereby playing a critical role in the spread of drug-resistance. 14n this study, class II integron was detected in 21% of the isolates.][17] In addition, the class I and II integrons were detected in 26 females and 6 male patients (32%) and 18 females and 3 male patients (21%), respectively.There were significant relationships between resistance to trimethoprimsulfamethoxazole (P < 0.001), ciprofloxacin (P < 0.01), and tetracycline (P < 0.005), and the class I integron.The class I integron gene was highly detected in the UPEC, possibly playing a role in the dissemination of drug resistance.
In Ranjbaran and colleagues' study, the prevalence of class I and II integrons in 100 isolates of E. coli was 86% and 8%, respectively. 18The higher existence of class I integron among drug-resistant isolates and a possible association with multiple drug resistance is a phenomenon that requires more investigations.

Conclusion
Because of the significant association found between the presence of class I integron among multidrug-resistant isolates and antibiotic resistance, infection control, and establishment and implementation of appropriate strategies for suitable treatment in hospitals are essential for the prevention of dissemination of these isolates.

Authors' Contributions
All the authors contributed equally to this study.