A review of colistin-resistant Escherichia coli isolates in the Middle East: mechanisms, epidemiology, and dissemination from different sources in humans, animals, foodand soil

1. Introduction

E. coli is a normal intestinal inhabitantthat can cause various diseases ,such as intestinal, urinary tract, bladder, and systemic infections in humans and animals ( 1 ). The prevalence of multidrug-resistant (MDR)and extensively drug-resistant (XDR) germs and the diversity of resistance profiles of E. coli isolates with extended β-lactamase spectrum (ESBL) and carbapenemase-producing germs (CP-Ec) have increased worldwide, which is of concern. Therefore, a new replacement drug is needed. Colistin (polymyxin E) is increasingly used as a ‘last’ treatment option for infections with Gram-negative MDR/XDR bacteria and as ‘“rescue therapy” when essentially no other options are available ( 2 ). Its mode of action is based on the binding of polymyxins to the LPS of the outer membrane of Gram-negative bacteria and the competitive displacement of divalent cations (Ca²⁺ and Mg²⁺) from the negativelycharged phosphate groups of lipid A of the LPS (Figure 1), leading to changes in cell membrane permeability and bacterial cell death . It seems likely that Gram-negative enteric bacteria from livestock and poultry can be transmitted to humans via handling or use of food of animal origin, leading to the spread of colistin resistance ( 3 ). Eggs and broilers have always been traded and transported in different countries around the world. This trade leads to the spread of antibiotic resistance by multidrug resistant organisms (MDRO_s), resulting in their global spread when an MDRO is offered into the production chain (Figure 2) ( 4 ). A progressive increase in colistin resistance may be associated with the extensive use of colistin in animal husbandry and veterinary medicine, which can spread rapidly through horizontal plasmid transfer ( 1 ). The lack of innovation in the development of new antibiotics for Gram-negative MDR/XDR pathogens has forced clinicians to reuse colistindespite its renal toxicity. Colistin has been used primarily in veterinary medicine for decades to treat Enterobacterales infections ( 4 ). Inappropriate use of colistin and other classes of antibiotics combined with inadequate infection control, especially in developing countries, can lead to serious in public health complications ( 1 , 5 ). To reduce the burden of resistance, studying the distribution of colistin resistance in Gram-negative bacteria ,such as E. coli strains should be the main focus of infection control in most countries. In this review, we determined the prevalence of colistin-resistant E. coli isolates in the Middle East based on literature reviews and positive reports, which are occuring at an alarming rate. There are few reliable epidemiological data on colistin-resistant E. coli isolates, and information on colistin-resistant E. coli from Asia, the largest, most populous, and most diverse continent in the world, is generally limited compared with Europe and the United States of America. The aim of this study was to provide an overview of the epidemiological characteristics of colistin-resistant E. coli isolates and to disseminate the pattern of colistin-resistant genes in E. coli isolates of different origins from the Middle East.

Figure 1. Mechanisms of act and resistance to colistin in Gram-negative bacteria.

Figure 2. Circulation and dissemination of colistin-resistant Escherichia coli harboring mcr genes or either even harboring chromosomal genes, between environment, food, animals, and humans.

2. Mechanism of colistin resistance

Colistin is a cationic, amphipathic molecule containing a non- ribosomally synthesized decapeptide and a lipid tail. Colistin binds to the anionic phosphate groups of the lipid A portion of lipopolysaccharides (LPS) through electrostatic interactions in Gram-negative bacteriaand destabilizes the outer membrane. In recent years, numerous studies have pointed to several outbreaks of infections caused by colistin-resistant bacteria. Until 2015, mutations in chromosomal genes were the only known mechanism for acquired colistin resistance. In November 2015, the plasma- borne phosphoethanolamine (pEtN) transferase mcr-1, a horizontally transmissible, plasmid-mediated colistin resistance gene, was first spotted ( 6 ). MCR-1 is a membrane-bound enzyme consisting of five hydrophobic transmembrane helices and a soluble form in the periplasmic space. MCR-1 adds a PEA group to the 1(4’) phosphate of glucosamine units in LPSlipid A of the bacterial outer membrane via a putative ping-pong mechanism (Figure 1) ( 7 ). After the discovery of the mcr-1 gene, nine other mcr gene types (mcr-2 to mcr -10) carried by plasmids with different replicon types were detected in isolates from different bacterial species ( 8 ). Single nucleotide mutations in the phoP/Q, pmrAB, mgrB, acrB, LpX ACD genespreviously detected colistin-resistant Klebsiella spp. and E. coli isolatesare known “hotspots” for mutations, whereby they may reduce bacterial membrane affinity for cationic polymyxin (Figure 1). Nucleotide positions with an unusually high mutation frequency are referred to as mutation “hotspots”( 9 ). However, all of these genes have evolved resistance to colistin. Gram-negative pathogens are able to induce cationic changes at phosphate groups in the lipid A components of LPS, which induces resistance to the action of polymyxins. On the other hand, relatively little is known about the mechanisms of colistin resistance in E. coli, apart from the acquisition of mcr genes. PhoPQThe phoPQ expression in E. coli is controlled not only by MgrB but also by the sRNA MicA, which adds to the mechanisms controlling PhoPQ activation and may contribute less than deletion or inactivation of mgrB to colistin resistance. Colistin resistance in clinical E. coli strains has previously been associated only with BasRS resistance mutations in E. coli. The two-component system PmrAB (BasRS) plays a key role in mediating the modification of LPS that leads to colistin resistance in Gram-negative bacteria. In E. coli strains, activation of BasRS leads to increased expression of several operons, including eptA, which encodes a lipid A-specific phosphoethanolamine transferase ( 10 ). These point mutations are associated with colistin use. In contrast, plasmid-mediated resistance is a constant resistance unrelated to colistin use. It is essential, not only for E. coli but also for Pseudomonas aeruginosa and Klebsiella pneumonia. Thus,mutations in pmrAB genes lead to an increase in MIC values against colistin, and the presence of mcr-1 in isolates resulted in a four- to eightfold increase in colistin MIC ( 11 ) Details are shown in Figure 1.

3. A review of the occurrence and spread of colistin-resistant E. coli and associated mechanisms in the Middle East

In the current study, we searched the available data on the molecular mechanisms and prevalence of colistin-resistant Ecoli isolates in the Middle East. Using the keywords colistin resistance, Escherichia coli, molecular mechanism, Middle Eastern countries, relevant scientific articles were searched in PubMed, Google Scholar, andScopus databases, which are popular search engines in medical sciences in English. The searches were conducted between 2010-2023. All studies included in our survey are summarized in Table 1. In this study, we designed the scheme of the plasmid- encoded colistin-resistant genemcr1, and the other companion genesthat may be present together with the mcr-1 gene (Figure 3).

Figure 3. Schematic representation of plasmid-encoded colistin-resistant gene, mcr-1, and the other accompanying genes, like some genetic elements, insertions sequences, and other antibiotic resistance genes, can be transported with the mcr1 gene inside a plasmid.

3.1. Iran:

Recently, a study was conducted in Iran, and for the first time, mcr-1 was detedcted in E. coli isolates rom livestock and wastewater ( 12 ). In a recent study, 37 (10.8%) colistin-resistant E. coli isolates were detected (MIC values >2 mg/L) and 36 fingerprint patterns were identified in colistin-resistant E. coli using ERIC- PCR ( 13 ) (Table 1).

3.2. Egypt:

In a study conducted in broiler poultry farms in Egypt the mcr-1 gene was detected in 18 of 28 E. coli isolates( 14 ). In 2019-2020 mcr-1 was detected in chicken farms ( 15 ) and also in patients with urinary tract infections( 16 ). Of 38 animal isolates tested, only one E. coli isolate was positive for the mcr-1 gene. It is noteworthy that the presence of the mcr-1 gene was confirmed for the first time in Egypt (accession no. LC114017), belonging to ST10 ( 17 ). in another work, four mcr-1-positive colistin-resistant E. coli were detected in 200 samples of Karish cheese, belonging to the dominant uropathogenic E. coli ST69 lineage. In addition, the plasmid pEGY1-MCR-1 was part of the IncHI2 incompatibility group found in this study. This was consistent with data from the Kingdom of Saudi Arabia and Qatar, suggesting a possible distribution of pEGY1-MCR-1-like plasmids in the Middle East ( 18 ). In a study conducted by Zaki et al. 50 Enterobacterales species resistant to colistin. E. coli isolates (21/50) shown resistance to colistin were investigated with an MIC >2 mg/L. An E. coli strain carrying mcr-1 was associated with colistin MIC >16 mg/L( 11 ). In a recent study, colistin resistance genes (mcr-1 and mcr-2) were detected in E. coli isolates from migratory birds, water sources, and humans. Data suggest that colistin resistance genes (mcr-1,2) are on the rise in water sources, humans and, animals ( 19 ). In addition, the mcr-1 gene was detected in a blaNDM‑1-positive E. coli strain of 18 colistin-resistant E. coli isolates. Other carbapenemases (KPC, VIM, IMP, SIM, GIM, and SPM) were not detected. None of the 18 colistin-resistant E. coli isolates carried the mcr-2 gene. mgrB genes were detected by PCR, and mgrB mutations were not found in colistin-resistant E. coli strains. The MIC of colistin by broth microdilution was ≥ 4 mg/L for an mcr1-positive E. coli strain. The mcr-1 gene was 100% identical to the known mcr-1 sequence (Genbank: NG_050417.1, Liu et al., 2016) ( 20 ). Among the 128 colistin-resistant strains, one mcr1-positive MDR E. coli isolate (MC13) was observed from beef sausage samples. In this study, the mcr-1 gene was located on an IncI2-type self-congugating plasmid with a size of 64.6 kb ( 21 ).

3.3. Turkey:

In 2019 mcr-1 was reported in retail raw chicken meat ( 22 ). The first report of E. coli carrying the mcr-1 gene, with colistin MICs of >8 mg/L, was reported from Turkey by Kurekci et al (2018) ( 23 ). A three-year study of ICU samples showed that 99%, 100%, and 99% of E. coli strains were sensitive to colistin in 2014, 2015, and 2016, respectively ( 24 ).

3.4. Oman and Kuwait:

Mohsin et al. reportedan E. coli isolate (OM97) carrying the mcr-1 gene with an MICof 4 mg/L. The mcr-1 gene was located on an IncI2-type congugative plasmid with a size of 63722bp size ( 25 ). In another study, four colistin-resistant E. coli strains with MICs of ≥2 mg/L had mcr-1 genes. These mcr-1 genes were found in the countries of Bahrain (two isolates), Saudi Arabia (one isolate), and the United Arab Emirates (one isolate). A colistin-resistant E. coli strain from Saudi Arabia carried the carbapenemase gene bla_NDM-1,and the. E. coli strain from the United Arab Emirates also carried a bla_CTX-M-64 gene. Three colistin-resistant E. coli strains carried mcr-1 on IncI2=type plasmids. In the fourth strain, mcr-1 was on a 240 kb IncHI2 plasmid in association with 13 other resistance genes ( 26 ).

3.5. Bahrain:

Of 50 E. coli strains, only 2 were colistin-resistant. In addition, 5 E. coli of the total E. coli isolates were found to have combined resistance to colistin and ( 27 ). In anotherstudy, 4 colistin-resistant E. coli strains were detected from 6 serial clinical isolates from a patient after a short hospital stay in Bahrain. WGS showed that the six isolates consisted of two different strains: a first ST-617 E. coli strain with mcr-1 and a second, mcr-1-negative ST-32 E. coli strain that emerged 2 weeks after the hospitalization. Thirteen antibiotic resistance genes were found in the ST-617 isolates. Manual broth microdilution and colistin E assay confirmed that four isolates carrying mcr1 had a colistin MIC of 0. 0004 mg/L ( 28 ).

3.6. Syria:

Lerner et.al. found in 2015 that an isolateof 10 carbapenemase-producing E. coli isolates obtained from wounded Syrian patients admitted to hospitals in northern Israel was non susceptible to colistin( 29 ).

3.7. Iraq:

Evaluation of antibiotic susceptibility of 430 E. coli strains isolated from three types of locally processed Iraqi dairy products revealed that 77 of 430 (18%) were resistant to colistin( 30 ).

3.8. Algeria:

The first report of mcr-1 in a colistin-resistant E. coli strain (breakpoint for resistance: >2mg/l ) in Algeria was published in 2016;this strain was collected in 2011. Also in this strain, bla_CTX-M15 and bla_TEM-1 were detected with mcr-1 ( 31 ). The transfer of fertilizers from animals to soil and irrigation water are important sources of colistin-resistant E. coli strains on farmsand can lead to a mixture of multiple antibioticresistance and pose a threat to human health. In this study, mcr1,3 genes were detected in 8 colistin-resistant E.coli isolates (MIC ⩾2 mg/L). All eight E. coli isolates were not susceptible to amoxicillin, amoxicillin/clavulanic acid, ticarcillin, nalidixic acid, ciprofloxacin, gentamicin, trimethoprim/sulfamethoxazole, and rifamycin; two were also not susceptible to cefotaxime, cefepime and aztreonam, and these two isolates also carried the bla_TEM-12 gene in addition to mcr-1. The mcr-1-positive E. coli isolates were assigned to three STs, including ST10 (n = 3), ST405 (n = 2) and ST345 (n = 1), whilst the two isolates carrying the mcr-3 gene were dedicated to ST155( 32 ). Another study performed on 237 E. coli isolatesshowed that one strain was positive for the mcr-1 gene (MIC of colistin: 4 mg/L), but the isolates were negative in the RT-PCR assay targeting the mcr-2 to mcr-8 genes ( 33 ). Some studies have shown that environmental contamination is a worldwide problem. In 2016, two colistin-resistant E. coli were isolated from seawater in Algeria carrying the mcr-1 gene on a nonconjugative plasmid. After sequence typing, they were shown to belong to two different types of ST. The two strains were not sensitive to amoxicillin, ticarcillin, piperacillin, gentamicin, nalidixic acid, tigecycline, tetracycline, trimethoprim-sulfamethoxazole and, colistin. Two isolates had colistin MIC values of 4 mg/L and 8 mg/L ( 34 ). The colistin-resistant mcr-1-bearing E. coli (MIC of 4mg/L) was resistant to most antibiotics tested, including B-lactams (amoxicillin, amoxicillin -clavulanate, ticarcillin, cefepime, ceftriaxone, cefotaxime, and aztreonam), gentamicin, trimethoprim/sulfamethoxazole, sulfadiazine, rifampicin, and fluoroquinolones, but remainssensitive to carbapenems, amikacin, tigecycline, fosfomycin, and piperacillin/tazobactam. PCR and sequencing revealed that this isolate contained the bla_CTX-M-15, bla_TEM-1, and qnrB19 genes along with mcr-1 ( 35 ).

3.9. Qatar:

A colistin-resistant E. coli strain with resistance to polymyxin Band several lactams was detected. The colistin resistance gene mcr-1 was located on a 241-kb IncHI2 plasmid (GenBank accession number KU743384) ( 36 ). Tsui et al. reported two multidrug-resistant E. coli strains carrying the mcr-1 gene together with the bla_CTX-M-15 and bla_NDM-1 genes. These isolates were obtained from rectal swabs of pediatric patients ( 37 ). Three E. coli isolates showed resistance to colistin with MICs > 4 µg/mL in both Phoenix and SensiTest results. One E. coli isolate ( EC-12) harbored mcr-1.1 on the IncI2 plasmid pEC-12. In this study, acquired resistance to colistin via chromosomal (phoPQ, pmrAB, and mgrB) was found not to be involved in colistin-resistant E. coli strains ( 38 ).

3.10. Lebanon:

In Lebanon, mcr-1.26 was reported for the first time in an MDR E. coli isolated from chicken wings( 39 ). In a study conducted on food workers in Lebanon, mcr-1 was detected in six samples( 40 ). Another study was conducted on rectal swabs from residents of two Syrian refugee camps in Lebanon. The results of this study showed the clonal spread of mcr-1 among Syrian refugees ( 41 ). Five colistin-resistant E. coli were isolated from rectal swabs of 23 different patients (23clinical strains) treated with colistin-carbapenem combination therapy. The MIC of colistin ranged from 8 to 16 mg/L for the E. coli strains, with four E. coli strains achieving a MIC of 16mg/L. None of the strains carried mcr-1 to mcr-5. The associated colistin resistance genes, including mgrB, pmrA, pmrB, phoP, and phoQ, were amplified and sequenced because no mcr genes were present. In these E. coli strains, colistin resistance was associated with mutations in the pmrA, pmrB, phoP, and phoQ genes that resulted in amino acid changes ( 42 ). Of 105MDR E. coli isolates, 23 colistin-resistant E. coli strains were found, to be positive for mcr-1. 105 ESBLs/ampCs strains include E. coli that were not carbapenemase producers in this study. Four of the 23 strains were colistin-resistant in ESBL-producing E. coli. Of the four ESBL mcr-1-positive resistant isolates, CTX-M was detected in two strains, whereas SHV and TEM were detected in all four strains. All strains had a colistin MIC ≥ 0.002 mg/L. The MICs of 23 E. coli isolates were 4–16 mg/L, except for one strain with a MIC of 0.256 mg/L( 43 ). In the following study in Lebanon, the colistin MIC for the mcr-1-positive isolates ranged from 4 to 64 mg/L. In this study, the mcr-1 gene was located on plasmids belonging to IncI2 and IncX4, as well as IncF plasmids associated with the spread of antibiotic resistance and virulence genes among Enterobacterales. BlaTEM, bla_CTX-M, and bla_SHV were detected in 86%, 80.6%, and 13.8% of isolates, respectively. Genotyping of the mcr-1-positive E. coli isolates was performed using BOX-PCR fingerprinting analysis and all 36 isolates were classified into 25 different genotypes ( 44 ).

3.11. Saudi Arabia:

In a study conducted in Saudi Arabia,137 (51%) E. coli strains were detectedamong 415 uropathogenic isolates, of which 57 (41.6%) were classified as ESBL producers. Colistin resistance was detected in 9% of uropathogenic isolates, and a few levels were reported 45 in E. coli isolates ( 45 ). Recently, mcr-1 was detected in poultry meat in Saudi Arabia ( 46 ).

3.12. Jordan:

No significant data on colistin-resistant E. coli strains were found in this country .

3.13. United Arab Emirates:

An identified colistin-resistant E. coli isolate carried the mcr-1 gene on conjugative plasmids, which was discussed in the Oman and Kuwait section of this article ( 26 ).

3.14. Cyprus:

No significant data were found on colistin-resistant E. coli strains in this country .

4. Conclusion:

Many studies in the medical field have highlighted the crisis of antibiotic resistance in Enterobacteriaceae as far as resistance to colistin (last in the line of therapy) in pandrogen resistant (PDR) strains is concerned ( 9 ). The clinical use of colistin in severe nosocomial infections caused by XDR gram-negative bacteria, particularlycarbapenem-resistant strains, and subsequently colistin-resistant isolates of human origin, are often considered a treatment challenge. The worldwide spread of colistin-resistant gram-negative bacteria of animal origin is almost entirely due to food-producing animals, and is thought to be largely related to the overuse and misuse of antibiotics in veterinary medicine. Colistin resistance of animal origin could also potentially be transmitted to the human microbiome and clinical pathogens ( 47 ). Very little has been reported on the prevalence of colistin resistance in general. The percentage of mcr genes reported in E. coli strains has been presented globally (Figure 6). (https://card.mcmaster.ca/). In the last 10 years, almost all Middle Eastern countries have conducted studies on E. coli strains to determine the rate of colistin resistance. As far as we know, most colistin-resistant E. coli strains have been reported from Lebanon, Algeria and Egypt, perhaps because most studies on this topic have been conducted there (Figure 4). The highest number of mcr-1-positive E. coli strains was reported from Lebanon, Qatar, the Arabian Peninsula and Bahrain (Figure 5). It should be considered that inadequate sanitary conditions, overcrowding, and poor infection control practices in animals, as well as over-prescription of antibiotics in health care systems, may contribute to the huge massive of MDR strains ( 5 ). It appears that the presence of the mcr-1 gene is currently the most common strategy for colistin resistance in E. coli strains among the known mechanisms. The mcr-1 gene has been detected in various environmental sources, humans, food animals, and even immigrant birds in these countries. No clear evidence of chromosomal point mutations for colistin resistance analysis was found in E. coli isolates in the Middle East, except in one study. We also did not find a large number of documents on the existence of mcr-2-9 genes in this region. Althoughit appears thatthe rate of colistin resistance due to chromosomal genes was negligible in E. coli strains, further studies are needed to determine the true prevalence of chromosomal colistin resistance genes among E. coli isolates.

Figure 4. The percentage of colistin-resistant E. coli in middle East countries.

Figure 5. The numbers of mcr-1-positive in colistin-resistant E. coli in middle East countries.

Figure 6. Percentage of mcr genes reported in E. coli

In this study, most colistin-resistant E. coli isolates were found to have plasmid -mediated colistin resistance, mcr genes (especially mcr-1), compared with mutations in the pmrAB, phoPQ, and mgrB genes, in contrast to Klebsiella spp. There are new strategies to control MDR/XDR/PDR bacteria, including phage therapy, nanoparticles, aptamer, and combination therapy ( 48 ). According to some studies, the appropriate use of disinfectants (sodium hypochlorite 5%, chloroxylenol (Dettol) 4.8%, Sayasept-HP 2%, chlorhexidine 2%, and ethanol 70%) at the right concentrations for the different bacterial species should also be considered to avoid the induction of resistance mechanisms in bacteria( 49 ).

Acknowledgment

We thank Medical Microbiology Research Center, Qazvin University of Medical Science, Qazvin, Iran

Authors' Contribution

Farhad nikkhahi, Sara Rahimi, and Mehdi Bakht wrote the main manuscript text and Sara Rahimi, Zahra and Mehdi Bakht prepared figures and tables. All authors reviewed the manuscript

Ethics

Not applicable

Conflict of Interest

The authors have no conflicts of interest to declare

References

1. Trevizol JS, Martins BL, de Queiroz-Fernandes GM. Resistance to polymyxins in Escherichia coli. J Exp Clin Microbiol Vol. 2018; 1(1)
2. Niazadeh M, Nikkhahi F, Robatjazi S, Javadi A, Farzam SA, Babaei S, et al. Evaluation of mechanisms of colistin resistance in Klebsiella pneumoniae strains isolated from patients with urinary tract infection in ICU. Iranian journal of microbiology. 2022; 14(1)
3. Rhouma M, Beaudry F, Letellier A. Resistance to colistin: what is the fate for this antibiotic in pig production?. International journal of antimicrobial agents. 2016; 48(2):119-26.
4. Petrosillo N, Ioannidou E, Falagas M. Colistin monotherapy vs. combination therapy: evidence from microbiological, animal and clinical studies. Clinical Microbiology and Infection. 2008; 14(9):816-27.
5. Bakht M, Alizadeh SA, Rahimi S, Kazemzadeh Anari R, Rostamani M, Javadi A, et al. Phenotype and genetic determination of resistance to common disinfectants among biofilm-producing and non-producing Pseudomonas aeruginosa strains from clinical specimens in Iran. BMC microbiology. 2022; 22(1):1-16.
6. Berglund B. Acquired resistance to colistin via chromosomal and plasmid-mediated mechanisms in klebsiella pneumoniae. Infectious Microbes & Diseases. 2019; 1(1):10-9.
7. Li B, Yin F, Zhao X, Guo Y, Wang W, Wang P, et al. Colistin resistance gene mcr-1 mediates cell permeability and resistance to hydrophobic antibiotics. Frontiers in microbiology. 2020; 10:3015.
8. Du C, Feng Y, Wang G, Zhang Z, Hu H, Yu Y, et al. Co-Occurrence of the mcr-1.1 and mcr-3.7 Genes in a Multidrug-Resistant Escherichia coli Isolate from China. Infection and Drug Resistance. 2020; 13:3649.
9. Aghapour Z, Gholizadeh P, Ganbarov K, Bialvaei AZ, Mahmood SS, Tanomand A, et al. Molecular mechanisms related to colistin resistance in Enterobacteriaceae. Infection and drug resistance. 2019; 12:965.
10. Janssen AB, Bartholomew TL, Marciszewska NP, Bonten MJ, Willems RJ, Bengoechea JA, et al. Nonclonal emergence of colistin resistance associated with mutations in the BasRS two-component system in Escherichia coli bloodstream isolates. Msphere. 2020; 5(2)
11. Zaki M, ElKheir N, Mofreh M. Molecular study of colistin resistant clinical isolates of Enterobacteriaceae species. J Clin Mol Med. 2018; 1(1):1-4.
12. Nikkhahi F, Robatjazi S, Niazadeh M, Javadi A, Shahbazi G, Aris P, et al. First detection of mobilized colistin resistance mcr-1 gene in Escherichia coli isolated from livestock and sewage in Iran. New Microbes and New Infections. 2021; 41:100862.
13. Moosavian M, Emam N. The first report of emerging mobilized colistin-resistance (mcr) genes and ERIC-PCR typing in Escherichia coli and Klebsiella pneumoniae clinical isolates in southwest Iran. Infection and drug resistance. 2019; 12:1001.
14. Abdel-Rahman MA, Hamed EA, Abdelaty MF, Sorour HK, Badr H, Hassan WM, et al. Distribution pattern of antibiotic resistance genes in Escherichia coli isolated from colibacillosis cases in broiler farms of Egypt. Veterinary World. 2023; 16(1):1.
15. Badr H, Samir A, El-Tokhi EI, Shahein MA, Rady FM, Hakim AS, et al. Phenotypic and Genotypic Screening of Colistin Resistance Associated with Emerging Pathogenic Escherichia coli Isolated from Poultry. Veterinary Sciences. 2022; 9(6):282.
16. Zakaria AS, Edward EA, Mohamed NM. Genomic insights into a colistin-resistant uropathogenic Escherichia coli strain of O23: H4-ST641 lineage harboring mcr-1.1 on a conjugative IncHI2 plasmid from Egypt. Microorganisms. 2021; 9(4):799.
17. Khalifa HO, Ahmed AM, Oreiby AF, Eid AM, Shimamoto T, Shimamoto T. Characterisation of the plasmid-mediated colistin resistance gene mcr-1 in Escherichia coli isolated from animals in Egypt. International journal of antimicrobial agents. 2016; 47(5):413-4.
18. Hammad AM, Hoffmann M, Gonzalez-Escalona N, Abbas NH, Yao K, Koenig S, et al. Genomic features of colistin resistant Escherichia coli ST69 strain harboring mcr-1 on IncHI2 plasmid from raw milk cheese in Egypt. Infection, Genetics and Evolution. 2019; 73:126-31.
19. Ahmed ZS, Elshafiee EA, Khalefa HS, Kadry M, Hamza DA. Evidence of colistin resistance genes (mcr-1 and mcr-2) in wild birds and its public health implication in Egypt. Antimicrobial Resistance & Infection Control. 2019; 8(1):1-8.
20. Zafer MM, El-Mahallawy HA, Abdulhak A, Amin MA, Al-Agamy MH, Radwan HH. Emergence of colistin resistance in multidrug-resistant Klebsiella pneumoniae and Escherichia coli strains isolated from cancer patients. Annals of clinical microbiology and antimicrobials. 2019; 18(1):1-8.
21. Sadek M, Poirel L, Nordmann P, Nariya H, Shimamoto T, Shimamoto T. Draft genome sequence of an mcr-1/IncI2-carrying multidrug-resistant Escherichia coli B1: ST101 isolated from meat and meat products in Egypt. Journal of global antimicrobial resistance. 2020; 20:41-2.
22. Adiguzel MC, Baran A, Wu Z, Cengiz S, Dai L, Oz C, et al. Prevalence of colistin resistance in Escherichia coli in Eastern Turkey and genomic characterization of an mcr-1 positive strain from retail chicken meat. Microbial Drug Resistance. 2021; 27(3):424-32.
23. Kurekci C, Aydin M, Nalbantoglu OU, Gundogdu A. First report of Escherichia coli carrying the mobile colistin resistance gene mcr-1 in Turkey. Journal of global antimicrobial resistance. 2018; 15:169-70.
24. Yürüyen C, Yanılmaz Ö, Boz E, Aksaray S. Surveillance of resistance in the intensive care units using a cumulative antibiogram. Mikrobiyoloji bulteni. 2018; 52(4):329-39.
25. Mohsin J, Pál T, Petersen JE, Darwish D, Ghazawi A, Ashraf T, et al. Plasmid-mediated colistin resistance gene mcr-1 in an Escherichia coli ST10 bloodstream isolate in the Sultanate of Oman. Microbial Drug Resistance. 2018; 24(3):278-82.
26. Sonnevend Á, Ghazawi A, Alqahtani M, Shibl A, Jamal W, Hashmey R, et al. Plasmid-mediated colistin resistance in Escherichia coli from the Arabian Peninsula. International Journal of Infectious Diseases. 2016; 50:85-90.
27. Saeed NK, Alkhawaja S, Azam NFAEM, Alaradi K, Al-Biltagi M. Epidemiology of carbapenem-resistant Enterobacteriaceae in a Tertiary Care Center in the Kingdom of Bahrain. Journal of laboratory physicians. 2019; 11(2):111.
28. Snesrud E, Ong AC, Corey B, Kwak YI, Clifford R, Gleeson T, et al. Analysis of serial isolates of mcr-1-positive Escherichia coli reveals a highly active ISApl1 transposon. Antimicrobial agents and chemotherapy. 2017; 61(5)
29. Lerner A, Solter E, Rachi E, Adler A, Rechnitzer H, Miron D, et al. Detection and characterization of carbapenemase-producing Enterobacteriaceae in wounded Syrian patients admitted to hospitals in northern Israel. European Journal of Clinical Microbiology & Infectious Diseases. 2016; 35(1):149-54.
30. Abbar F, Kadder HK. Incidence of antibiotic resistant Escherichia coli in Iraqi milk products. Journal of food protection. 1990; 53(10):846-8.
31. Berrazeg M, Hadjadj L, Ayad A, Drissi M, Rolain J-M. First detected human case in Algeria of mcr-1 plasmid-mediated colistin resistance in a 2011 Escherichia coli isolate. Antimicrobial agents and chemotherapy. 2016; 60(11):6996.
32. Touati M, Hadjadj L, Berrazeg M, Baron SA, Rolain JM. Emergence of Escherichia coli harbouring mcr-1 and mcr-3 genes in North West Algerian farmlands. Journal of global antimicrobial resistance. 2020; 21:132-7.
33. Nabti LZ, Sahli F, Hadjadj L, Ngaiganam EP, Lupande-Mwenebitu D, Rolain J-M, et al. Autochthonous case of mobile colistin resistance gene mcr-1 from a uropathogenic Escherichia coli isolate in Sétif Hospital, Algeria. Journal of global antimicrobial resistance. 2019; 19:356-7.
34. Drali R, Berrazeg M, Zidouni LL, Hamitouche F, Abbas AA, Deriet A, et al. Emergence of mcr-1 plasmid-mediated colistin-resistant Escherichia coli isolates from seawater. Science of the total environment. 2018; 642:90-4.
35. Bachiri T, Lalaoui R, Bakour S, Allouache M, Belkebla N, Rolain JM, et al. First report of the plasmid-mediated colistin resistance gene mcr-1 in Escherichia coli ST405 isolated from wildlife in Bejaia, Algeria. Microbial Drug Resistance. 2018; 24(7):890-5.
36. Forde BM, Zowawi HM, Harris PN, Roberts L, Ibrahim E, Shaikh N, et al. Discovery of mcr-1-Mediated colistin resistance in a highly Virulent Escherichia coli Lineage. Msphere. 2018; 3(5)
37. Tsui CK, Sundararaju S, Al Mana H, Hasan MR, Tang P, Perez-Lopez A. Plasmid-mediated colistin resistance encoded by mcr-1 gene in Escherichia coli co-carrying bla CTX-M-15 and bla NDM-1 genes in pediatric patients in Qatar. Journal of global antimicrobial resistance. 2020; 22:662-3.
38. Eltai NO, Kelly B, Al-Mana HA, Ibrahim EB, Yassine HM, Al Thani A, et al. Identification of mcr-8 in Clinical Isolates From Qatar and Evaluation of Their Antimicrobial Profiles. Frontiers in microbiology. 2020; 11:1954.
39. Kassem II, Osman M, Hassan J, Sulaiman AA, Mann D, Esseili MA, et al. First report of the mobile colistin resistance gene, mcr-1.26, in multidrug-resistant Escherichia coli isolated from retail chicken meat. Journal of Global Antimicrobial Resistance. 2023; 34:176-8.
40. Al-Mir H, Osman M, Drapeau A, Hamze M, Madec J-Y, Haenni M. Spread of ESC-, carbapenem-and colistin-resistant Escherichia coli clones and plasmids within and between food workers in Lebanon. Journal of Antimicrobial Chemotherapy. 2021; 76(12):3135-43.
41. Azour A, Al-Bayssari C, Dagher TN, Fajloun F, Fajloun M, Rolain J-M. Clonal Dissemination of Plasmid-Mediated Carbapenem and Colistin Resistance in Refugees Living in Overcrowded Camps in North Lebanon. Antibiotics. 2021; 10(12):1478.
42. Dagher TN, Al-Bayssari C, Chabou S, Baron S, Hadjadj L, Diene SM, et al. Intestinal carriage of colistin-resistant Enterobacteriaceae at Saint Georges Hospital in Lebanon. Journal of global antimicrobial resistance. 2020; 21:386-90.
43. Dandachi I, Fayad E, El-Bazzal B, Daoud Z, Rolain J-M. Prevalence of extended-Spectrum Beta-lactamase-producing gram-negative bacilli and emergence of mcr-1 Colistin resistance gene in Lebanese swine farms. Microbial Drug Resistance. 2018; 25(2):233-40.
44. Kassem II. First report on the detection of the plasmid-borne colistin resistance gene mcr-1 in multi-drug resistant E. coli isolated from domestic and sewer waters in Syrian refugee camps in Lebanon. Travel medicine and infectious disease. 2019; 30:117-20.
45. Taher I, Almaeen A, Aljourfi H, Bohassan E, Helmy A, El-Masry E, et al. Surveillance of antibiotic resistance among uropathogens in Aljouf region northern Saudi Arabia. Iranian journal of microbiology. 2019; 11(6):468.
46. Yasir M, Qureshi AK, Kensarah EA, Bibi F, Al-Zahrani IA, Abd El Ghany M, et al. Draft genome sequence of colistin-resistant and extended-spectrum β-lactamase (ESBL)-producing multidrug-resistant Escherichia coli isolated from poultry meat. Journal of Global Antimicrobial Resistance. 2021; 27:112-4.
47. Economou V, Gousia P. Agriculture and food animals as a source of antimicrobial-resistant bacteria. Infection and drug resistance. 2015; 8:49.
48. Rahimi S, Bakht M, Javadi A, Foroughi F, Marashi SMA, Nikkhahi F. Characterization of novel bacteriophage PSKP16 and its therapeutic potential against β-lactamase and biofilm producer strain of K2-Hypervirulent Klebsiella pneumoniae pneumonia infection in mice model. BMC microbiology. 2023; 23(1):1-22.
49. Bakht M, Alizadeh SA, Rahimi S, Kazemzadeh Anari R, Rostamani M, Javadi A, et al. Phenotype and genetic determination of resistance to common disinfectants among biofilm-producing and non-producing Pseudomonas aeruginosa strains from clinical specimens in Iran. BMC microbiology. 2022; 22(1):124.
50. Elnahriry SS, Khalifa HO, Soliman AM, Ahmed AM, Hussein AM, Shimamoto T, et al. Emergence of plasmid-mediated colistin resistance gene mcr-1 in a clinical Escherichia coli isolate from Egypt. Antimicrobial agents and chemotherapy. 2016; 60(5):3249.
51. Karami P, Mohajeri P, Mashouf RY, Karami M, Yaghoobi MH, Dastan D, et al. Molecular characterization of clinical and environmental Pseudomonas aeruginosa isolated in a burn center. Saudi journal of biological sciences. 2019; 26(7):1731-6.
52. Moawad AA, Hotzel H, Neubauer H, Ehricht R, Monecke S, Tomaso H, et al. Antimicrobial resistance in Enterobacteriaceae from healthy broilers in Egypt: emergence of colistin-resistant and extended-spectrum β-lactamase-producing Escherichia coli. Gut pathogens. 2018; 10(1):1-12.
53. El-Mokhtar MA, Daef E, Mohamed Hussein AA, Hashem MK, Hassan HM. Emergence of nosocomial pneumonia caused by Colistin-resistant Escherichia coli in patients admitted to chest intensive care unit. Antibiotics. 2021; 10(3):226.
54. Ayaz ND, Cufaoglu G, Yonsul Y, Goncuoglu M, Erol I. Plasmid-Mediated Colistin Resistance in Escherichia coli O157: H7 Cattle and Sheep Isolates and Whole-Genome Sequence of a Colistin-Resistant Sorbitol Fermentative Escherichia coli O157: H7. Microbial Drug Resistance. 2019; 25(10):1497-506.
55. Alfouzan W, Dhar R, Nicolau DP. In Vitro activity of newer and conventional antimicrobial agents, including fosfomycin and colistin, against selected Gram-negative bacilli in Kuwait. Pathogens. 2018; 7(3):75.
56. Loucif L, Chelaghma W, Cherak Z, Bendjama E, Beroual F, Rolain J-M. Detection of NDM-5 and MCR-1 antibiotic resistance encoding genes in Enterobacterales in long-distance migratory bird species Ciconia ciconia, Algeria. Science of The Total Environment. 2022; 814:152861.
57. Chelaghma W, Loucif L, Bendjama E, Cherak Z, Bendahou M, Rolain J-M. Occurrence of Extended Spectrum Cephalosporin-, Carbapenem-and Colistin-Resistant Gram-Negative Bacteria in Fresh Vegetables, an Increasing Human Health Concern in Algeria. Antibiotics. 2022; 11(8):988.
58. Chaalal N, Touati A, Yahiaoui-Martinez A, Aissa MA, Sotto A, Lavigne J-P, et al. Colistin-resistant Enterobacterales isolated from chicken meat in Western Algeria. Microbial Drug Resistance. 2021; 27(7):991-1002.