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Review

Molecular Mechanisms of Colistin Resistance in Africa: A Systematic Review of Literature

by
Ahmed Olowo-Okere
1 and
Abdourahamane Yacouba
2,*
1
Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
2
Faculté des Sciences de la Santé, Université Abdou Moumouni, P.M.B.10896, Niamey, Niger
*
Author to whom correspondence should be addressed.
GERMS 2020, 10(4), 367-379; https://doi.org/10.18683/germs.2020.1229
Submission received: 11 April 2020 / Revised: 30 June 2020 / Accepted: 21 July 2020 / Published: 28 December 2020
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Abstract

Introduction: Updated and comprehensive data on the mechanism underlying colistin resistance is lacking in Africa. Literature search: Herein, we aimed to review available literature on the molecular mechanisms of colistin resistance in Africa. PubMed, Google Scholar, and African Journal online databases were searched on the 15th of January 2020 for original research articles that reported mechanisms of colistin resistance in any of the 54 African countries. Review: Of the 1473 studies identified through initial database search, 36 met the inclusion criteria. Colistin resistance was mostly observed in Escherichia coli isolated from human clinical samples. Plasmid-mediated colistin resistance mechanism (26; 72.2%) was the most frequently reported resistance mechanism. About three-quarters (27; 75.0%) of the 36 studies were done in North Africa. In this zone, the mobilized colistin resistance (mcr) genes were mostly detected in E. coli harboring three plasmid types, IncHI2, IncI2, and IncX 4, from animal samples (n = 9; 42.8%). Of the six studies performed in Southern Africa, four reported mcr-1 mostly detected from human samples (n = 2; 50.0%) in E. coli isolates carrying IncHI2, IncI2, and IncX 4 with diverse range of STs. One hitherto unknown mutation, the mutation in the I527N gene was detected in colistin resistant isolates in this region, which was absent in colistin susceptible isolates. In West and Central Africa, two and one studies, respectively, reported mcr-1 gene exclusively in Escherichia coli isolates. Conclusions: Transferable plasmid mediated colistin resistance is rapidly emerging in Africa with mcr-1 as the predominant genetic variant in human, animals, and environmental samples.

Introduction

The emergence of multidrug resistant bacterial infections is one of the greatest threats today to the global public health [1]. It arises naturally as one of the direct consequences of antibiotic use [2]. Its abuse particularly in animal production and aquaculture has further driven the emergence and spread of antibiotic resistance, leading healthcare practice towards a post- antibiotic era [3]. Resistance to all important classes of antibiotics including carbapenems, has been reported particularly among the clinically important pathogens, the ESCAPE pathogens, with substantial impact on morbidity, mortality and attendant increase in healthcare cost [4]. Further exacerbating the problem is the lack of new antibiotics classes in the pipeline, owing to decline in research and development of new effective anti-infective agents [5]. Consequent upon this, old antibiotics such as colistin, which were initially abandoned due to patient safety concerns, were recalled as a life-saving and last resort measure against serious Gram-negative bacterial infections [6].
Colistin is one of the five polymyxin antibiotics originally isolated in 1947 from the soil bacterium Paenibacillus polymyxa subsp. Colistinus [7]. It is a polycationic lipopolypeptide that acts by competitively displacing divalent cations, Mg2+ and Ca2+, from the phosphate group of lipopolysaccharides of Gram-negative cell envelope, thereby disrupting cell membrane integrity and leading to leakage of important cellular components and ultimately bacterial cell death [7]. It has also been shown to act by inhibiting a key respiratory enzyme, type II NADH-quinone oxidoreductases (NDH-2) [7]. Colistin is highly and rapidly bactericidal against susceptible bacterial species particularly Pseudomonas aeruginosa, Acinetobacter baumannii and most members of Enterobacteriaceae family with the exception of Providencia spp., Morganella morganii, Proteus spp., Serratia marcescens, among others which are naturally resistant [8].
Until recently, acquired resistance to colistin has been mostly due to chromosomal mutation in the PmrA/PmrB and PhoP/PhoQ two- component regulatory systems, or through increased production of capsular polysaccharide [8]. Mutational inactivation of mgrB, a negative regulator of the PhoP/PhoQ signaling system has also been identified in several studies as a basis for colistin resistance [8,9,10]. The transferable plasmid encoded colistin resistance (the mobilized colistin resistance or mcr-1) emerged in China in late 2015 [11]. Today, nine other families of mcr genes have been detected from various hosts and pathogens range [9,10,12]. The mcr genes have now been globally disseminated and it continues to be increasingly reported worldwide [13].
While the molecular mechanisms underlying colistin resistance have been described considerably in North America, Europe and more particularly in Asia, updated and comprehensive data on the different mechanisms of colistin resistance are lacking in Africa. We therefore aimed to systematically review available literature on the molecular mechanisms of colistin resistance in African countries, to determine the most prevalent colistin resistance mechanisms, the circulating colistin resistant Gram-negative bacteria clones and hosts in Africa.

Methods

Literature search

A systematic literature search was conducted to identify articles reporting colistin resistance in Africa. Multiple searches were conducted in PubMed, Google Scholar, and African Journal online (AJOL). Our search strategy uses different relevant keywords: “colistin resistance” OR “mobilized colistin resistance gene” OR “mcr” AND Africa, or names of the 54 African countries. The present study was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [14].

Study selection

Publications identified were considered up to 15 January 2020. Searches undertaken were not restricted by language. Two authors independently performed the literature search. After removing duplicates, the studies identified in the initial search were first screened by title and abstract and retained if they met the predefined inclusion criteria, as follows: (i) original article published or accepted in a peer- reviewed journal, (ii) studies that described mechanism of colistin resistance in humans, animals and environment, and (iii) studies conducted in any of the 54 Africa countries. Full text of the articles that met the inclusion criteria were retrieved and further screened. Studies that reported phenotypic prevalence of colistin resistance without investigation of molecular basis underlying the resistance were excluded. Also, studies conducted outside the specified period of this systematic review were excluded. The screening process was documented in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow chart of the study selection.

Data extraction

Two reviewers independently extracted the relevant data, using a standardized collection form to extract data from the included articles. The following data were extracted from each study: name of country in which the study was conducted, the first author’s name, year of publication, sources of isolates (human/animal/environment), bacterial species, plasmid type, genes detected, number of mcr positive bacteria, sequences types (ST), number of isolates exhibiting colistin resistance, medical condition (for human), and result of antibiotic susceptibility testing.

Data analysis

The data collected, including the countries, sources of isolates, bacterial species, plasmid type, genes detected, number of mcr genes positive bacteria, and sequences types (ST), were analysed using Microsoft Excel 2013. Descriptive statistics including frequencies and percentages were used in the analysis.

Results

Literature search and study selection

A total of 1493 non duplicate, potentially relevant studies were identified and retrieved from the databases. After screening of the titles and abstracts, 1414 articles were considered irrelevant and excluded. Of the 59 full text articles considered of interest and assessed for eligibility, only 36 articles met the inclusion criteria and were included in the final analysis (Figure 1). Based on the included studies, the first article on colistin resistance in Africa was published in 2014.

Characteristics and distribution of studies describing colistin resistance in Africa

This systematic review involved a total of 36 studies conducted in seven countries namely Tunisia (n = 7), South Africa (n = 6), São Tomé and Príncipe (n = 1), Nigeria (n = 2), Libya (n = 1), Egypt (n = 8), and Algeria (n = 11) (Figure 2). The studies were published between 2014 and 2019. The studies documented colistin resistance mechanisms in bacterial isolates obtained from humans (21; 58.3%), animals (10; 27.8%) and environmental samples (3; 8.3%). In the included studies, colistin resistance mechanism was described in mainly three bacterial species comprising A. baumannii, Escherichia coli and Klebsiella pneumoniae. Colistin resistance was most frequently observed in E. coli isolated from human clinical samples. Both chromosomal and plasmid mediated mechanisms were reported, with plasmid-mediated colistin resistance mechanism (26; 72.2%) most frequently reported (Figure 3).
Overall, the studies described colistin resistance in 904 bacterial isolates, 188 (20.79%) of which harbored various mcr genes. Of the 188 mcr genes detected, mcr-1 was the most prevalent. Among the 188 isolates in which the presence of mcr genes has been reported, 88 (46.80%) reported the types of plasmid. The mcr genes were mostly harbored on an IncHI2 plasmid (n = 50; 56.82%), followed by IncI2 (n = 19; 21.59%).

Distribution of mcr genes in various Africa regions

North Africa

About three-quarters (27; 75.0%) of the 36 studies were done in North Africa. The prevalence of mcr genes was 17.53% among colistin resistant isolates. A total of 21 studies reported mcr genes in three countries: Tunisia (n = 5), Egypt (n = 8), and Algeria (n = 8) (Figure 2). The mcr genes included mcr-1 (n = 18; 85.9%), mcr- 1 and mcr-2 (n = 1; 4.7%), mcr-1 and mcr-3 (n = 1; 4.7%), and mcr-8 (n = 1; 4.7%). The mcr genes were equally detected from samples obtained from animals (n = 9; 42.8%) and humans (n = 9; 42.8%). The presence of mcr genes was reported in only Escherichia coli and Klebsiella pneumoniae. Four plasmid types were reported. All of them were reported from Escherichia coli and harbored mcr-1 with IncHI2 (n = 3) as the most prevalent mcr associated plasmid encountered in North Africa (Table 1).
The most commonly reported sequence type was ST10 reported in all three countries. Tunisia reported the most diverse range of STs (8 types), followed by Algeria (5 types). The presence of mgrB mutation was detected in Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Acinetobacter baumannii.

Southern Africa

In Southern African, six (16.6%) of the 36 studies were conducted in the region. The prevalence of mcr genes was 31.85% among colistin resistant isolates. Four studies reported mcr genes, exclusively mcr-1. They were mostly detected from human samples (n = 2; 50.0%) followed by animal sample (n = 1; 25.0%), environment sample (n = 1; 50%) and food (n = 1; 4.4%). Diverse range (8 types) of STs including ST1, ST10, ST14, ST57, ST101, ST226, ST624, ST1007 were reported. The presence of mcr-1 genes was reported in Escherichia coli and Klebsiella pneumoniae. Three plasmid types including IncHI2, IncI2, and IncX4 were reported. The three plasmids were contained in E. coli isolates and harbored mcr-1 (Table 2). Interestingly, one hitherto unknown mutation, the mutation in the I527N was detected in colistin resistant isolates in this region, which was absent in colistin susceptible isolates. Since then, this gene has not been detected in other regions.
West Africa
In the West Africa region, only 2 (5.5%) of the 36 studies reported the mechanism of colistin resistance during the study period. The two studies were conducted in Nigeria and exclusively reported mcr-1 genes in Escherichia coli isolates (Table 3). The prevalence of mcr genes was 26.92% among colistin resistant isolates. The genes were detected from human sample (n= 1; 50.0%) and multiple sources sample (n = 1; 50.0%). The plasmid and sequence type were not determined.
Central Africa
In this region, only a study conducted in São Tomé and Príncipe reported the mechanism of colistin resistance. This study reported the isolation of an Escherichia coli ST1408 isolate from a human sample which harbored mcr-1 on an IncX4 plasmid (Table 4).

Discussion

Until recently, acquired resistance to colistin has been mostly due to chromosomal mutation. The transferable plasmid encoded colistin resistance emerged in China in late 2015 [11]. Since then, eight other families of mcr genes have been detected from various hosts and pathogens range across the world [9,15]. As illustrated in this study, the diversity of colistin resistance mechanisms in the various African countries is also changing.
Our finding showed that mcr genes have been reported in six African countries. The lack of data from several African countries may not be unconnected with lack of/inadequate laboratory capacity for their detection. The emergence of these transferable colistin resistance mechanisms may be attributed firstly to the high use of colistin as growth promoters, prophylactic and other agricultural use in many African countries [16]. In a survey conducted by World Organization for Animal Health, 15% of African countries authorized the use of antibiotics including colistin in food animals [16]. Secondly, the importation of food from countries including France and China where colistin resistance is endemic may have also contributed to the emergence of colistin resistance [13,17]. Importation of antibiotic resistant bacteria across geographical regions has been well documented in the literature [18]. China for example is Africa’s leading commercial partner. Thus, there are large travel volumes through which the transferable plasmid encoded colistin resistance could reach the continent. Algeria, Egypt, Nigeria and South Africa were China’s most important trading partners in Africa and consequently the countries at highest importation risk [19].
In this study, the mcr genes bearing bacteria were prevalently reported in Escherichia coli and Klebsiella pneumoniae. The predominance of Escherichia coli among the isolates bearing mcr genes is consistent with a result of a previously published systematic review of literature on the global burden of mcr genes [13]. Similarly, another study systematic review in Latin America and Caribbean showed that mcr genes were more predominantly harbored by Escherichia coli [20]. The prevalence of Escherichia coli and Klebsiella pneumoniae among mcr bearing isolates in this study may be related to the source of exposure of the isolates to colistin. Colistin contained in food animal’s feeds is usually the source of exposure of gut bacteria particularly Escherichia coli and Klebsiella pneumoniae to colistin [17].
Similar to reports of studies in Europe [21], IncHI2 is the most frequently reported mcr bearing plasmid type in African countries. Moreover, IncHI2 plasmids are especially known for co-localization of various antibiotic resistance determinants [22]. This plasmid has been isolated from contaminated food, animals and water, thereby supporting the fact that the global trade of food and animals is a major vehicle for dissemination of mcr genes and other antibiotic resistance genes in Africa [23]. Thirdly, since antibiotic use, no matter how appropriate, contributes to antibiotic resistance, over prescription of polymyxins by health workers as alternative to carbapenem as a last resort agent against MDR Gram-negative bacteria infections may have contributed also to the rapidly emerging transferable colistin resistance in Africa [13].
Findings from this study show that most of the studies that reported mcr genes were performed in North Africa. This may be due beside the aforementioned factors, to the North African countries’ collaboration and proximity with Europe, particularly with France. As we all know, these countries are low- or middle-income countries with poor medical and healthcare infrastructure. The proximity to Europe may account for the high prevalence of mcr genes in North Africa as the mcr bearing bacterial species could be easily imported due to high human and materials traffic between the countries. Also, the cordial collaboration between North Africa and Europe ensures access to state-of-the-art healthcare facility and improved human capacity for detection of this emerging resistance mechanism.
Of the ten families of mcr genes detected from various hosts and pathogens range in the world, four including mcr-1, mcr-2, mcr-3 and mcr-8 were detected in Africa. Similar to a report from other regions around the world [24], ST10 is the dominant ST in both animals and environmental samples. The ST10 bearing bacteria are known to co-produce other antibiotic inactivating enzymes such as ESBLs and carbapenemase [25,26]. This may have wide range implication on the management of infections caused by these bacteria.
This systematic review is limited by a number of factors. First, this review reports data from studies published in electronic databases and indexed in Google Scholar, PubMed and AJOL. Several unpublished theses and dissertations and articles published in traditional local print journals could not be assessed and so they were not included. Secondly, studies reporting the burden of colistin resistance without the corresponding report of the molecular basis of the resistance were excluded. As such, the burden of mcr genes in Africa may have been underestimated. Nevertheless, this systematic review is the first to determine the Africa wide burden and distribution of mcr genes. It thus provides a baseline data on this rapidly emerging resistance mechanism.

Conclusions

This study shows that the transferable plasmid mediated colistin resistance is rapidly emerging in Africa with mcr-1 as the predominant genetic variant in human, animals as well as in the environmental samples. This is worrisome in a continent where alternative antibiotics are rarely available. Therefore, there is urgent need to establish African-wide antibiotic stewardship and intensify efforts to preserve the efficacy of colistin as a last resort antibiotic.

Author Contributions

AY and AO conceived and designed the study. AO collected the data. AY analyzed the data; AY and AO drafted and revised the manuscript. All authors read and approved the final version of the manuscript.

Funding

This research received no external funding.

Conflicts of interest

The authors declare no conflict of interest.

References

  1. Ventola, C.L. The antibiotic resistance crisis: Part 1: Causes and threats. P T 2015, 40, 277–283. [Google Scholar] [PubMed]
  2. Roca, I.; Akova, M.; Baquero, F.; et al. Corrigendum to “The global threat of antimicrobial resistance: Science for intervention” [New Microbes New Infect 6 (2015): 22–29]. New Microbes New Infect 2015, 8, 175. [Google Scholar] [CrossRef] [PubMed]
  3. World Health Organization (WHO). Antimicrobial Resistance: Global Report on Surveillance 2014. Available online: http://www.who.int/antimicrobial-resistance/publications/surveillancereport/en/ (accessed on 5 May 2020).
  4. Matsunaga, N.; Hayakawa, K. Estimating the impact of antimicrobial resistance. Lancet Glob Health 2018, 6, e934–e935. [Google Scholar] [CrossRef]
  5. Högberg, L.D.; Heddini, A.; Cars, O. The global need for effective antibiotics: Challenges and recent advances. Trends Pharmacol Sci 2010, 31, 509–515. [Google Scholar] [CrossRef] [PubMed]
  6. Karaiskos, I.; Lagou, S.; Pontikis, K.; Rapti, V.; Poulakou, G. The “old” and the “new” antibiotics for MDR Gram- negative pathogens: For whom, when, and how. Front Public Health 2019, 7, 151. [Google Scholar] [CrossRef]
  7. Poirel, L.; Jayol, A.; Nordmann, P. Polymyxins: Antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes. Clin Microbiol Rev 2017, 30, 557–596. [Google Scholar] [CrossRef]
  8. Olaitan, A.O.; Morand, S.; Rolain, J.M. Mechanisms of polymyxin resistance: Acquired and intrinsic resistance in bacteria. Front Microbiol 2014, 5, 643. [Google Scholar] [CrossRef]
  9. Aghapour, Z.; Gholizadeh, P.; Ganbarov, K.; et al. Molecular mechanisms related to colistin resistance in Enterobacteriaceae. Infect Drug Resist 2019, 12, 965–975. [Google Scholar] [CrossRef]
  10. Olaitan, A.O.; Diene, S.M.; Kempf, M.; et al. Worldwide emergence of colistin resistance in Klebsiella pneumoniae from healthy humans and patients in Lao PDR, Thailand, Israel, Nigeria and France owing to inactivation of the PhoP/PhoQ regulator mgrB: An epidemiological and molecular study. Int J Antimicrob Agents 2014, 44, 500–507. [Google Scholar] [CrossRef]
  11. Liu, Y.Y.; Wang, Y.; Walsh, T.R.; et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study. Lancet Infect Dis 2016, 16, 161–168. [Google Scholar] [CrossRef]
  12. Wang, C.; Feng, Y.; Liu, L.; Wei, L.; Kang, M.; Zong, Z. Identification of novel mobile colistin resistance gene mcr-10. Emerg Microbes Infect 2020, 9, 508–516. [Google Scholar] [CrossRef]
  13. Elbediwi, M.; Li, Y.; Paudyal, N.; et al. Global burden of colistin-resistant bacteria: Mobilized colistin resistance genes study (1980–2018). Microorganisms 2019, 7, 461. [Google Scholar] [CrossRef]
  14. Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G.; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009, 6, e1000097. [Google Scholar] [CrossRef]
  15. Nabti, L.Z.; Sahli, F.; Ngaiganam, E.P.; et al. Development of real-time PCR assay allowed describing the first clinical Klebsiella pneumoniae isolate harboring plasmid-mediated colistin resistance mcr-8 gene in Algeria. J Glob Antimicrob Resist 2020, 20, 266–271. [Google Scholar] [CrossRef] [PubMed]
  16. Van, T.T.H.; Yidana, Z.; Smooker, P.M.; Coloe, P.J. Antibiotic use in food animals worldwide, with a focus on Africa: Pluses and minuses. J Glob Antimicrob Resist 2020, 20, 170–177. [Google Scholar] [CrossRef]
  17. Kempf, I.; Jouy, E.; Chauvin, C. Colistin use and colistin resistance in bacteria from animals. Int J Antimicrob Agents 2016, 48, 598–606. [Google Scholar] [CrossRef] [PubMed]
  18. Grami, R.; Mansour, W.; Mehri, W.; et al. Impact of food animal trade on the spread of mcr-1-mediated colistin resistance, Tunisia, July 2015. Euro Surveill 2016, 21, 30144. [Google Scholar] [CrossRef] [PubMed]
  19. Nowak, W. China-Africa and India-Africa trade in the years 2000–2014. Procedia Econ Finance 2016, 39, 140–146. [Google Scholar] [CrossRef]
  20. Mendes Oliveira, V.R.; Paiva, M.C.; Lima, W.G. Plasmid- mediated colistin resistance in Latin America and Caribbean: A systematic review. Travel Med Infect Dis 2019, 31, 101459. [Google Scholar] [CrossRef]
  21. Hartl, R.; Kerschner, H.; Lepuschitz, S.; Ruppitsch, W.; Allerberger, F.; Apfalter, P. Detection of the mcr-1 gene in a multidrug-resistant Escherichia coli isolate from an Austrian patient. Antimicrob Agents Chemother 2017, 61, e02623-16. [Google Scholar] [CrossRef]
  22. Li, R.; Xie, M.; Lv, J.; Wai-Chi Chan, E.; Chen, S. Complete genetic analysis of plasmids carrying mcr-1 and other resistance genes in an Escherichia coli isolate of animal origin. J Antimicrob Chemother 2017, 72, 696–699. [Google Scholar] [CrossRef]
  23. Arcilla, M.S.; van Hattem, J.M.; Matamoros, S.; et al. Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis 2016, 16, 147–149. [Google Scholar] [CrossRef] [PubMed]
  24. Wang, X.; Liu, Y.; Qi, X.; et al. Molecular epidemiology of colistin-resistant Enterobacteriaceae in inpatient and avian isolates from China: High prevalence of mcr- negative Klebsiella pneumoniae. Int J Antimicrob Agents 2017, 50, 536–541. [Google Scholar] [CrossRef] [PubMed]
  25. Aibinu, I.; Odugbemi, T.; Koenig, W.; Ghebremedhin, B. Sequence type ST131 and ST10 complex (ST617) predominant among CTX-M-15-producing Escherichia coli isolates from Nigeria. Clin Microbiol Infect 2012, 18, E49–E51. [Google Scholar] [CrossRef]
  26. Falgenhauer, L.; Imirzalioglu, C.; Oppong, K.; et al. Detection and characterization of ESBL-producing Escherichia coli from humans and poultry in Ghana. Front Microbiol 2019, 9, 3358. [Google Scholar] [CrossRef] [PubMed]
  27. Bakour, S.; Olaitan, A.O.; Ammari, H.; et al. Emergence of colistin- and carbapenem-resistant Acinetobacter baumannii ST2 clinical isolate in Algeria: First case report. Microb Drug Resist 2015, 21, 279–285. [Google Scholar] [CrossRef]
  28. Hammad, A.M.; Hoffmann, M.; Gonzalez-Escalona, N.; et al. Genomic features of colistin resistant Escherichia coli ST69 strain harboring mcr-1 on IncHI2 plasmid from raw milk cheese in Egypt. Infect Genet Evol 2019, 73, 126–131. [Google Scholar] [CrossRef]
  29. Bachiri, T.; Lalaoui, R.; Bakour, S.; et al. First report of the plasmid-mediated colistin resistance gene mcr-1 in Escherichia coli ST405 isolated from wildlife in Bejaia, Algeria. Microb Drug Resist 2018, 24, 890–895. [Google Scholar] [CrossRef]
  30. Saidani, M.; Messadi, L.; Sahmin, E.; et al. ESBL- and mcr-1- producing Escherichia coli in veal calves in Tunisia. J Glob Antimicrob Resist 2019, 19, 104–105. [Google Scholar] [CrossRef]
  31. Saidani, M.; Messadi, L.; Chaouechi, A.; et al. High genetic diversity of Enterobacteriaceae clones and plasmids disseminating resistance to extended-spectrum cephalosporins and colistin in healthy chicken in Tunisia. Microb Drug Resist 2019, 25, 1507–1513. [Google Scholar] [CrossRef]
  32. Chabou, S.; Leulmi, H.; Rolain, J.M. Emergence of mcr-1- mediated colistin resistance in Escherichia coli isolates from poultry in Algeria. J Glob Antimicrob Resist 2019, 16, 115–116. [Google Scholar] [CrossRef] [PubMed]
  33. Maamar, E.; Alonso, C.A.; Hamzaoui, Z.; et al. Emergence of plasmid-mediated colistin-resistance in CMY-2-producing Escherichia coli of lineage ST2197 in a Tunisian poultry farm. Int J Food Microbiol 2018, 269, 60–63. [Google Scholar] [CrossRef]
  34. Khalifa, H.O.; Ahmed, A.M.; Oreiby, A.F.; Eid, A.M.; Shimamoto, T.; Shimamoto, T. Characterisation of the plasmid-mediated colistin resistance gene mcr-1 in Escherichia coli isolated from animals in Egypt. Int J Antimicrob Agents 2016, 47, 413–414. [Google Scholar] [CrossRef] [PubMed]
  35. Touati, M.; Hadjadj, L.; Berrazeg, M.; Baron, S.A.; Rolain, J.M. Emergence of Escherichia coli harbouring mcr-1 and mcr-3 genes in North West Algerian farmlands. J Glob Antimicrob Resist 2020, 21, 132–137. [Google Scholar] [CrossRef]
  36. Hassen, B.; Saloua, B.; Abbassi, M.S.; et al. mcr-1 encoding colistin resistance in CTX-M-1/CTX-M-15- producing Escherichia coli isolates of bovine and caprine origins in Tunisia. First report of CTX-M-15-ST394/D E. coli from goats. Comp Immunol Microbiol Infect Dis 2019, 67, 101366. [Google Scholar] [CrossRef]
  37. Yanat, B.; Machuca, J.; Yahia, R.D.; Touati, A.; Pascual, Á.; Rodríguez-Martínez, J.-M. First report of the plasmid- mediated colistin resistance gene mcr-1 in a clinical Escherichia coli isolate in Algeria. Int J Antimicrob Agents 2016, 48, 760–761. [Google Scholar] [CrossRef] [PubMed]
  38. 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. Antimicrob Agents Chemother 2016, 60, 6996–6997. [Google Scholar] [CrossRef]
  39. Elnahriry, S.S.; Khalifa, H.O.; Soliman, A.M.; et al. Emergence of plasmid-mediated colistin resistance gene mcr-1 in a clinical Escherichia coli isolate from Egypt. Antimicrob Agents Chemother 2016, 60, 3249–3250. [Google Scholar] [CrossRef]
  40. Nabti, L.Z.; Sahli, F.; Hadjadj, L.; et al. Autochthonous case of mobile colistin resistance gene mcr-1 from a uropathogenic Escherichia coli isolate in Sétif Hospital, Algeria. J Glob Antimicrob Resist 2019, 19, 356–357. [Google Scholar] [CrossRef]
  41. Osama, R.; Bakeer, W.; Fadel, S.; Amin, M. Association of carbapenem and colistin resistance in pathogenic Gram negative bacteria. J Pure Appl Microbiol 2019, 13, 733–739. [Google Scholar] [CrossRef]
  42. Drali, R.; Berrazeg, M.; Zidouni, L.L.; et al. Emergence of mcr-1 plasmid-mediated colistin-resistant Escherichia coli isolates from seawater. Sci Total Environ 2018, 642, 90–94. [Google Scholar] [CrossRef]
  43. Zafer, M.M.; El-Mahallawy, H.A.; Abdulhak, A.; Amin, M.A.; Al-Agamy, M.H.; Radwan, H.H. Emergence of colistin resistance in multidrug-resistant Klebsiella pneumoniae and Escherichia coli strains isolated from cancer patients. Ann Clin Microbiol Antimicrob 2019, 18, 40. [Google Scholar] [CrossRef]
  44. Ahmed, Z.S.; Elshafiee, E.A.; Khalefa, H.S.; Kadry, M.; Hamza, D.A. Evidence of colistin resistance genes (mcr-1 and mcr-2) in wild birds and its public health implication in Egypt. Antimicrob Resist Infect Control 2019, 8, 197. [Google Scholar] [CrossRef] [PubMed]
  45. Mansour, W.; Haenni, M.; Saras, E.; et al. Outbreak of colistin-resistant carbapenemase-producing Klebsiella pneumoniae in Tunisia. J Glob Antimicrob Resist 2017, 10, 88–94. [Google Scholar] [CrossRef] [PubMed]
  46. Jaidane, N.; Bonnin, R.A.; Mansour, W.; et al. Genomic insights into colistin-resistant Klebsiella pneumoniae from a Tunisian teaching hospital. Antimicrob Agents Chemother 2018, 62, e01601–e01617. [Google Scholar] [CrossRef]
  47. Yousfi, H.; Hadjadj, L.; Dandachi, I.; et al. Colistin- and carbapenem-resistant Klebsiella pneumoniae clinical isolates: Algeria. Microb Drug Resist 2018, 25, 258–263. [Google Scholar] [CrossRef] [PubMed]
  48. Belbel, Z.; Lalaoui, R.; Bakour, S.; Nedjai, S.; Djahmi, N.; Rolain, J.M. First report of colistin resistance in an OXA- 48- and a CTX-M-15 producing Klebsiella pneumoniae clinical isolate in Algeria due to PmrB protein modification and mgrB inactivation. J Glob Antimicrob Resist 2018, 14, 158–160. [Google Scholar] [CrossRef]
  49. El Sayed Zaki, M.; Abou ElKheir, N.; Mofreh, M. Molecular study of colistin resistant clinical isolates of Enterobacteriaceae species. J Clin Mol Med 2018, 1, 1–4. [Google Scholar] [CrossRef]
  50. El-Sokkary, R.H.; Gebriel, M.G. Colistin susceptibility and the effect of colistin-sulfadiazine combination among multidrug resistant E. coli and K. pneumoniae at Egyptian intensive care units. Egypt J Med Microbiol 2019, 28, 87–93. [Google Scholar] [CrossRef]
  51. Kieffer, N.; Ahmed, M.O.; Elramalli, A.K.; et al. Colistin- resistant carbapenemase-producing isolates among Klebsiella spp. and Acinetobacter baumannii in Tripoli, Libya. J Glob Antimicrob Resist 2018, 13, 37–39. [Google Scholar] [CrossRef]
  52. Snyman, Y.; Whitelaw, A.C.; Reuter, S.; Dramowski, A.; Maloba, M.R.B.; Newton-Foot, M. Clonal expansion of colistin-resistant Acinetobacter baumannii isolates in Cape Town, South Africa. Int J Infect Dis 2020, 91, 94–100. [Google Scholar] [CrossRef] [PubMed]
  53. Perreten, V.; Strauss, C.; Collaud, A.; Gerber, D. Colistin resistance gene mcr-1 in avian pathogenic Escherichia coli in South Africa. Antimicrob Agents Chemother 2016, 60, 4414–4415. [Google Scholar] [CrossRef]
  54. Poirel, L.; Kieffer, N.; Brink, A.; Coetze, J.; Jayol, A.; Nordmann, P. Genetic features of MCR-1-producing colistin-resistant Escherichia coli isolates in South Africa. Antimicrob Agents Chemother 2016, 60, 4394–4397. [Google Scholar] [CrossRef]
  55. Newton-Foot, M.; Snyman, Y.; Maloba, M.R.B.; Whitelaw, A.C. Plasmid-mediated mcr-1 colistin resistance in Escherichia coli and Klebsiella spp. clinical isolates from the Western Cape region of South Africa. Antimicrob Resist Infect Control 2017, 6, 78. [Google Scholar] [CrossRef]
  56. Jayol, A.; Poirel, L.; Brink, A.; Villegas, M.V.; Yilmaz, M.; Nordmann, P. Resistance to colistin associated with a single amino acid change in protein PmrB among Klebsiella pneumoniae isolates of worldwide origin. Antimicrob Agents Chemother 2014, 58, 4762–4766. [Google Scholar] [CrossRef]
  57. Igwaran, A.; Iweriebor, B.C.; Okoh, A.I. Molecular characterization and antimicrobial resistance pattern of Escherichia coli recovered from wastewater treatment plants in Eastern Cape South Africa. Int J Environ Res Public Health 2018, 15, 1237. [Google Scholar] [CrossRef]
  58. Otokunefor, K.; Tamunokuro, E.; Amadi, A. Molecular detection of mobilized colistin resistance (mcr-1) gene in Escherichia coli isolates from Port Harcourt, Nigeria. J Appl Sci Environ Manage 2019, 23, 401–405. [Google Scholar] [CrossRef]
  59. Olowe, O.A.; Olowe, R.A.; Oluremi, A.S.; Adefioye, O.J. A novel report of colistin-resistant Escherichia coli carrying mcr-1 gene from animal and human feacal samples in Nigeria. Pan Afr J Life Sci 2018, 1, 7–10. [Google Scholar] [CrossRef]
  60. Poirel, L.; Aires-de-Sousa, M.; Kudyba, P.; Kieffer, N.; Nordmann, P. Screening and characterization of multidrug-resistant Gram-negative bacteria from a remote African area, São Tomé and Príncipe. Antimicrob Agents Chemother 2018, 62, e01021–18. [Google Scholar] [CrossRef] [PubMed]
Germs 10 00367 g001
Figure 1. Literature research and study selection.
Figure 1. Literature research and study selection.
Germs 10 00367 g001
Germs 10 00367 g002
Figure 2. Geographical distribution of the study countries.
Figure 2. Geographical distribution of the study countries.
Germs 10 00367 g002
Germs 10 00367 g003
Figure 3. Characteristics of colistin resistance in Africa.
Figure 3. Characteristics of colistin resistance in Africa.
Germs 10 00367 g003
Table 1. Distribution of the studies describing colistin resistance in North Africa.
Table 1. Distribution of the studies describing colistin resistance in North Africa.
CountryYearSourceOrganismNumber of Isolates Exhibiting Colistin ResistanceMechanismPlasmidGenes DetectedNumber of Isolates Positives for mcr GenesSTReferences
Algeria2014HumanAcinetobacter baumannii1ChromosomalNAPmrBNAND[27]
Egypt2019FoodEscherichia coli1PlasmidIncHI2A and
IncHI2		mcr-11ST69[28]
Algeria2017AnimalEscherichia coli1PlasmidNDmcr-11ST405[29]
Tunisia2019AnimalEscherichia coli5PlasmidIncHI2mcr-15ST162[30]
Tunisia2019AnimalEscherichia coli1PlasmidIncHI2mcr-11ND[31]
Algeria2016AnimalEscherichia coli5PlasmidNDmcr-13ND[32]
Tunisia2016AnimalEscherichia coli37PlasmidIncHI2mcr-137ST4[18]
Tunisia2018AnimalEscherichia coli2PlasmidIncI1 and incPmcr-12ST2197[33]
Egypt2016AnimalEscherichia coli1PlasmidNDmcr-11ST10[34]
Algeria2019EnvironmentEscherichia coli103PlasmidNDmcr-1, mcr-36ST10, ST155, ST345
and
ST405		[35]
Tunisia2019AnimalEscherichia coli4PlasmidNDmcr-14ST1642[36]
Algeria2016HumanEscherichia coli1PlasmidIncFIBmcr-11ST405[37]
Algeria2016HumanEscherichia coli6plasmidNDmcr-11ST405[38]
Egypt2016HumanEscherichia coli1PlasmidNDmcr-11ST1011[39]
Algeria2019HumanEscherichia coli1PlasmidNDmcr-11ND[40]
Egypt2019HumanEscherichia coli5Plasmid and chromosomalNDmcr-1, pmrA, pmrB1ND[41]
Algeria2018EnvironmentEscherichia coli246PlasmidNDmcr-12ND[42]
Egypt2019HumanEscherichia coli, Klebsiella pneumoniae40Plasmid and chromosomalNDmcr-1, mgrb2ST11[43]
Egypt2019AnimalEscherichia coli, Klebsiella34 #PlasmidNDmcr-1,34ND[44]
pneumoniae mcr-2
Tunisia2017HumanKlebsiella pneumoniae7ChromosomalNAmgrbNAND[45]
Tunisia2018HumanKlebsiella pneumoniae13ChromosomalNAmgrbNAND[46]
Algeria2018HumanKlebsiella pneumoniae3ChromosomalNAmgrb, pmrA/BNAST101[47]
Algeria2019HumanKlebsiella pneumoniae1PlasmidNDmcr-81ND[15]
Algeria2018HumanKlebsiella pneumoniae2ChromosomalNAmgrb, pmrBNAST2620
and
ST3242		[48]
Egypt2018HumanEscherichia coli, Klebsiella pneumoniae50PlasmidNDmcr-12ND[49]
Egypt2019HumanEscherichia coli34PlasmidNDmcr-11ND[50]
Libya2018HumanKlebsiella pneumoniae, Acinetobacter baumannii, Klebsiella oxytoca11ChromosomalNAmgrbNAST101[51]
NA—not applicable; ND—not determined; ST—sequence type. # This figure corresponds to the number of resistance genes found because the study didn’t specify the exact number of isolates resistant to colistin.
Table 2. Distribution of the studies describing colistin resistance in Southern Africa.
Table 2. Distribution of the studies describing colistin resistance in Southern Africa.
CountryYearSourceOrganismNumber of Isolates Exhibiting Colistin ResistanceMechanismPlasmidGenes DetectedNumber of Isolates Positives for mcr GenesSTReferences
South
Africa		2020HumanAcinetobacter baumannii26ChromosomalNAI527NNAST1[52]
South Africa2016AnimalEscherichia coli108PlasmidIncI2mcr-119ND[53]
South Africa2016HumanEscherichia coli7PlasmidIncHI2,
incI2,
IncX4		mcr-17ST10, ST1007, ST624, ST57, ST101, ST226[54]
South
Africa		2017HumanEscherichia coli, Klebsiella pneumoniae19PlasmidNDmcr-115ND[55]
South Africa2014HumanKlebsiella pneumoniae1ChromosomalNAPmrBNAST14[56]
South Africa2018EnvironmentEscherichia coli65PlasmidNDmcr-131ND[57]
NA—not applicable; ND—not determined; ST—sequence type.
Table 3. Distribution of the studies describing colistin resistance in West Africa.
Table 3. Distribution of the studies describing colistin resistance in West Africa.
CountryYearSourceOrganismNumber of Isolates Exhibiting Colistin ResistanceMechanismPlasmidGenes DetectedNumber of Isolates Positives for mcr GenesSTReferences
Nigeria2019HumanEscherichia coli21PlasmidNDmcr-12ND[58]
Nigeria2018Multiple sourcesEscherichia coli5PlasmidNDmcr-15ND[59]
ND—not determined; ST—sequence type.
Table 4. Distribution of the studies describing colistin resistance in Central Africa.
Table 4. Distribution of the studies describing colistin resistance in Central Africa.
CountryYearSourceOrganismNumber of Isolates Exhibiting Colistin
Resistance		MechanismPlasmidGenes DetectedNumber of Isolates Positives for mcr GenesSTReferences
São Tomé and
Príncipe		2018HumanEscherichia coli36PlasmidIncX4mcr-11ST1408[60]
ST—equence type.

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Olowo-Okere, A.; Yacouba, A. Molecular Mechanisms of Colistin Resistance in Africa: A Systematic Review of Literature. GERMS 2020, 10, 367-379. https://doi.org/10.18683/germs.2020.1229

AMA Style

Olowo-Okere A, Yacouba A. Molecular Mechanisms of Colistin Resistance in Africa: A Systematic Review of Literature. GERMS. 2020; 10(4):367-379. https://doi.org/10.18683/germs.2020.1229

Chicago/Turabian Style

Olowo-Okere, Ahmed, and Abdourahamane Yacouba. 2020. "Molecular Mechanisms of Colistin Resistance in Africa: A Systematic Review of Literature" GERMS 10, no. 4: 367-379. https://doi.org/10.18683/germs.2020.1229

APA Style

Olowo-Okere, A., & Yacouba, A. (2020). Molecular Mechanisms of Colistin Resistance in Africa: A Systematic Review of Literature. GERMS, 10(4), 367-379. https://doi.org/10.18683/germs.2020.1229

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