Integron and its role in antimicrobial resistance: A literature review on some bacterial pathogens

Document Type : Review Article


1 Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

2 Department of Microbiology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran

3 Student Research Committee, Pasteur Institute of Iran, Tehran, Iran

4 Department of Medical Biotechnology, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran

5 Department of Medical Biotechnology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran


In recent years, different acquired resistance mechanisms, including transposons, bacteriophages, plasmids, and integrons have been identified as involved in the spread of resistance genes in bacteria. The role of integrons as mobile genetic elements playing a central role in antibiotic resistance has been well studied and documented. Integrons are the ancient structures that mediate the evolution of bacteria by acquiring, storing, disposing, and resorting to the reading frameworks in gene cassettes. The term integron describes a large family of genetic elements, all of which are able to capture gene cassettes. Integrons were classified into three important classes based on integrase intI gene sequence. Integrons can carry and spread the antibiotic resistance genes among bacteria and are among the most significant routes of distribution of resistance genes via horizontal transfer. All integrons have three essential core features. The first feature is intI, the second one is an integron-associated recombination site, attI, and an integron-associated promoter, Pc, is the last feature. Among them, the class 1 integron is a major player in the dissemination of antibiotic resistance genes across pathogens and commensals. Various classes of integrons possessing a wide variety of gene cassettes are distributed in bacteria throughout the world. This review thus focuses on the distribution of integrons among important bacteria.


1. Osagie AE, Olalekan SH. Multiple Drug resistance: a fast-growing threat. Bio Med 2019;21: 2574 -1241.
2. Sütterlin S, Bray JE, Miaden MCJ, Tano E. Distribution of class 1 integrons in historic and contemporary collections of human pathogenic Escherichia coli. PLoS One 2020;15:e0233315.
3. Partridge SR, Tsafnat G, Coiera E, Iredell JR. Gene cassettes and cassette arrays in mobile resistance integrons. FEMS Microbiol Rev 2009;33:757-784.
4. Wu Y-W, Doak TG, Ye Y. The gain and loss of chromosomal integron systems in the treponema species. BMC Evol Biol 2013;13:16-24.
5. Ranjbar R, Taghipour F, Afshar D, Farshad S. Distribution of class 1 and 2 integrons among Salmonella enterica serovars isolated from iranian patients. Open Microbiol J 2019;13:63-66.
6. Koratzanis E, Souli M, Galani I, Chryssouli Z, Armaganidis A, Giamarellou H. Epidemiology and molecular characterisation of metallo-β-lactamase-producing Enterobacteriaceae in a university hospital Intensive Care Unit in Greece. Int J Antimicrob agents 2011;38:390-397.
7. Yu G, Li Y, Liu X, Zhao X, Li Y. Role of integrons in antimicrobial resistance: A review. Afr J Microbiol Res 2013;7:1301-1310.
8. Hall RM. Integrons and gene cassettes: hotspots of diversity in bacterial genomes. Ann N Y Acad Sci 2012;1267:71-78.
9. Escudero JA, Loot Cl, Nivina A, Mazel D. The integron: adaptation on demand. Microbiol Spectr 2015:139-161.
10. Gillings MR. Integrons: past, present, and future. Microbiol Mol Biol Rev 2014;78:257-277.
11. Xu Z, Li L, Shi L, Shirtliff ME. Class 1 integron in staphylococci. Mol biol Rep 2011;38:5261-5279.
12. Ke X, Gu B, Pan S, Tong M. Epidemiology and molecular mechanism of integron-mediated antibiotic resistance in Shigella. Arch Microbiol 2011;193:767-774.
13. Tansirichaiya S, Mullany P, Roberts AP. Promoter activity of ORF-less gene cassettes isolated from the oral metagenome. Sci Rep 2019;9:8388.
14. Recchia GD, Hall RM. Origins of the mobile gene cassettes found in integrons. Trends Microbiol 1997;5:389-394.
15. Larouche A, Roy PH. Effect of attC structure on cassette excision by integron integrases. Mob DNA 2011;2:3-15.
16. Ghaly TM, Geoghegan JL, Tetu SG, Gillings MR. The peril and promise of integrons: beyond antibiotic resistance. Trends Microbiol 2019; 28:455-464.
17. Stokes Ht, Hall RM. A novel family of potentially mobile DNA elements encoding site-specific gene-integration functions: integrons. Mol Microbiol 1989;3:1669-1683.
18. Labbate M, Case RJ, Stokes HW. The integron/gene cassette system: an active player in bacterial adaptation.  Methods Mol Biol 2009:103-125.
19. Deng Y, Bao X, Ji L, Chen L, Liu J, Miao J, et al. Resistance integrons: class 1, 2 and 3 integrons. Ann Clin Microbiol Antimicrob 2015;14:45-55.
20. Stalder T, Barraud O, Casellas M, Dagot C, Ploy M-C. Integron involvement in environmental spread of antibiotic resistance. Front  Microbiol 2012;3:119-132.
21. Bissonnette L, Roy PH. Characterization of In0 of Pseudomonas aeruginosa plasmid pVS1, an ancestor of integrons of multiresistance plasmids and transposons of Gram-negative bacteria. J Bacteriol 1992;174:1248-1257.
22. Mendes RE, Castanheira M, Toleman MA, Sader HS, Jones RN, Walsh TR. Characterization of an integron carrying blaIMP-1 and a new aminoglycoside resistance gene, aac (6′)-31, and its dissemination among genetically unrelated clinical isolates in a Brazilian hospital. Antimicrob Agents Chemother 2007;51:2611-2614.
23. Fluit A, Schmitz F-J. Resistance integrons and super-integrons. Clin Microbiol Infect 2004;10:272-288.
24. Xu Z, Li L, Shirtliff M, Peters B, Li B, Peng Y, et al. Resistance class 1 integron in clinical methicillin-resistant Staphylococcus aureus strains in southern China, 2001–2006. Clin Microbiol Infect 2011;17:714-718.
25. Ferdosi-Shahandashti E, Javanian M, Moradian-Kouchaksaraei M, Yeganeh B, Bijani A, Motevaseli E, et al. Resistance patterns of Escherichia coli causing urinary tract infection. Caspian J Intern Med 2015;6:148-151.
26. Martinez-Freijo P, Fluit A, Schmitz F, Grek V, Verhoef J, Jones M. Class I integrons in Gram-negative isolates from different European hospitals and association with decreased susceptibility to multiple antibiotic compounds. J Antimicrob Chemother 1998;42:689-696.
27. Domingues S, da Silva GJ, Nielsen KM. Global dissemination patterns of common gene cassette arrays in class 1 integrons. Microbiology (Reading) 2015;161:1313-1337.
28. Kadlec K, Schwarz S. Analysis and distribution of class 1 and class 2 integrons and associated gene cassettes among Escherichia coli isolates from swine, horses, cats and dogs collected in the BfT-GermVet monitoring study. J Antimicrob Chemother 2008;62:469-473.
29. Márquez C, Labbate M, Ingold AJ, Chowdhury PR, Ramírez MS, Centrón D, et al. Recovery of a functional class 2 integron from an Escherichia coli strain mediating a urinary tract infection. Antimicrob Agents Chemother 2008;52:4153-4154.
30. Kargar M, Mohammadalipour Z, Doosti A, Lorzadeh S, Japoni-Nejad A. High prevalence of class 1 to 3 integrons among multidrug-resistant diarrheagenic Escherichia coli in Southwest of Iran. Osong Public Health Res Perspect 2014;5:193-198.
31. Ahangarkani F, Rajabnia R, Shahandashti EF, Bagheri M, Ramez M. Frequency of class 1 integron in Escherichia coli strains isolated from patients with urinary tract infections in North of Iran. Mater Sociomed 2015;27:10-12.
32. Liu C-C, Tang CY, Chang K-C, Kuo H-Y, Liou M-L. A comparative study of class 1 integrons in Acinetobacter baumannii. Gene 2014;544:75-82.
33. Akrami F, Shahandashti EF, Yahyapour Y, Sadeghi M, Khafri S, Pournajaf A, et al. Integron types, genecassettes and antimicrobial resistance profile of Acinetobacter baumannii isolated from BAL samples in Babol, North of Iran. Microb Pathog 2017;109:35-38.
34. Deylam Salehi M, Ferdosi-Shahandashti E, Yahyapour Y, Khafri S, Pournajaf A, Rajabnia R. Integron-mediated antibiotic resistance in Acinetobacter baumannii isolated from intensive care unit patients, Babol, North of Iran. Bio Med Res Int 2017;2:1-8.
35. Gal-Mor O, Boyle EC, Grassl GA. Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ. Front Microbiol 2014;5:391-400.
36. Antunes P, Machado J, Peixe L. Characterization of antimicrobial resistance and class 1 and 2 integrons in Salmonella enterica isolates from different sources in Portugal. J Antimicrob Chemothe 2006;58:297-304.
37. Asgharpour F, Rajabnia R, Shahandashti EF, Marashi MA, Khalilian M, Moulana Z. Investigation of class I integron in Salmonella infantis and its association with drug resistance. Jundishapur J Microbiol 2014;7-???.
38. Wu H, Wang M, Liu Y, Wang X, Wang Y, Lu J, et al. Characterization of antimicrobial resistance in Klebsiella species isolated from chicken broilers. Int J Food Microbiol 2016;232:95-102.
39. Molana Z, FERDOSI SE, Gharavi S, Shafii M, Norkhomami S, Ahangarkani F, et al. Molecular investigation of class i integron in Klebsiella pneumoniae isolated from intensive care unit (shahid beheshti hospital of babol 2010). J Babol Univ Med Sci 2011;13:7-13.
40. Rajabnia R, Asgharpour F, Shahandashti EF, Moulana Z. Nosocomial emerging of (VIM1) carbapenemase-producing isolates of Klebsiella pneumoniae in North of Iran. Iran J Microbiol 2015;7:88-93.
41. Shahandashti EF, Molana Z, AsgharpourF, Mojtahedi A, Rajabnia R. Molecular detection of Integron genes and pattern of antibiotic resistance in Pseudomonas aeruginosa strains isolated from intensive care unit, Shahid Beheshti Hospital, North of Iran.  Int J Mol Cell Med 2012;1:209-217.
42. Moulana Z, Rajabnia R, Asgharpour F, Ferdosi Shahandashti E, Khalilian M, Norkhomami S. Class 1 integron in Pseudomonas aeruginosa isolates from different places and devices of ICU in Babol, Iran. Jundishapur J Microbiol 2013;6:138-143.
43. Sabbagh P, Ebrahimzadeh-Namvar A, Ferdosi-Shahandashti E, Javanian M, Khafri S, Rajabnia M. Molecular characterization of Staphylococcus aureus strains isolated among hospital staff nasal carriers of Babol, Iran. Caspian J Intern Med 2017;8:311-316.
44. Marathe N, Nagarkar S, Vaishampayan A, Rasane M, Samant S, Dohe V, et al. High prevalence of class 1 integrons in clinical isolates of methicillin‑resistant Staphylococcus aureus from India. Indian J Med Microbiol 2015;13:231-236.
45. Guo Y,  Song G,  Sun M, Wang J, Wang Y .Prevalence and Therapies of Antibiotic-Resistance in Staphylococcus aureus. Front Cell Infect Microbiol 2020;10:107.
46. Sow AG, Aïdara-Kane A, Barraud O, Gatet M, Denis F, Ploy M-C. High prevalence of trimethoprim-resistance cassettes in class 1 and 2 integrons in Senegalese Shigella spp. isolates. J Infect Dev Ctries 2010;4:207-212.