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Abstract
Acinetobacter baumannii has become a major cause of hospital-acquired infections with the rapid development of resistance to multiple antibiotics, including critical carbapenems. This resistance challenge limits treatment options and increases morbidity and mortality. The genetic plasticity of A. baumannii facilitates the mobilization of resistance genes via mobile genetic elements (MGE). Addressing this crisis requires a deeper understanding of the mechanisms by which MGE propagates carbapenem resistance. This paper provides a solution by systematically reviewing recent research on the role of MGE in disseminating resistance genes. Following PRISMA guidelines, a comprehensive literature review was conducted across various databases. The review revealed that resistance mechanisms primarily involve carbapenem-hydrolyzing enzymes and MGE, such as integrons, transposons, insertion sequences, and plasmids. Notably, genes like blaOXA-23 and blaNDM are frequently mobilized by these elements, facilitating horizontal gene transfer and persistence. Understanding the mechanisms of MGE-mediated gene transfer is crucial for developing strategies to control the spread of antibiotic resistance in A. baumannii.
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References
- Jiang, Y., Ding, Y., Wei, Y., Jian, C., Liu, J., & Zeng, Z. (2022). Carbapenem-resistant Acinetobacter baumannii: A challenge in the intensive care unit. Frontiers in Microbiology, 13, 1045206.
- Cavallo, I., Oliva, A., Pages, R., Sivori, F., Truglio, M., Fabrizio, G., Pasqua, M., Pimpinelli, F., & Di Domenico, E. G. (2023). Acinetobacter baumannii in the critically ill: complex infections get complicated. Frontiers in Microbiology, 14, 1196774.
- Nguyen, M., & Joshi, S. G. (2021). Carbapenem resistance in Acinetobacter baumannii, and their importance in hospital-acquired infections: a scientific review. Journal of Applied Microbiology, 131(6), 2715–2738.
- Mancuso, G., Midiri, A., Gerace, E., & Biondo, C. (2021). Bacterial antibiotic resistance: the most critical pathogens. Pathogens, 10(10), 1310.
- Venkateswaran, P., Vasudevan, S., David, H., Shaktivel, A., Shanmugam, K., Neelakantan, P., & Solomon, A. P. (2023). Revisiting ESKAPE Pathogens: virulence, resistance, and combating strategies focusing on quorum sensing. Frontiers in Cellular and Infection Microbiology, 13, 1159798.
- Singh, A., Tanwar, M., Singh, T. P., Sharma, S., & Sharma, P. (2024). An escape from ESKAPE pathogens: A comprehensive review on current and emerging therapeutics against antibiotic resistance. International Journal of Biological Macromolecules, 279, 135253.[7]
- WHO publishes list of bacteria for which new antibiotics are urgently needed. (n.d.). Retrieved July 17, 2024, from https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed
- Iovleva, A., Mustapha, M. M., Griffith, M. P., Komarow, L., Luterbach, C., Evans, D. R., Cober, E., Richter, S. S., Rydell, K., Arias, C. A., Jacob, J. T., Salata, R. A., Satlin, M. J., Wong, D., Bonomo, R. A., Van Duin, D., Cooper, V. S., Van Tyne, D., & Doi, Y. (2022). Carbapenem-Resistant Acinetobacter baumannii in U.S. Hospitals: Diversification of Circulating Lineages and Antimicrobial Resistance. MBio, 13(2).
- Aurilio, C., Sansone, P., Barbarisi, M., Pota, V., Giaccari, L. G., Coppolino, F., Barbarisi, A., Passavanti, M. B., & Pace, M. C. (2022). Mechanisms of Action of Carbapenem Resistance. Antibiotics, 11(3).
- Ahuatzin-Flores, O. E., Torres, E., & Chávez-Bravo, E. (2024). Acinetobacter baumannii, a Multidrug-Resistant Opportunistic Pathogen in New Habitats: A Systematic Review. Microorganisms 2024, Vol. 12, Page 644, 12(4), 644.
- Noel, H. R., Petrey, J. R., & Palmer, L. D. (2022). Mobile genetic elements in Acinetobacter antibiotic-resistance acquisition and dissemination. Annals of the New York Academy of Sciences, 1518(1), 166–182.
- Partridge, S. R., Kwong, S. M., Firth, N., & Jensen, S. O. (2018). Mobile Genetic Elements Associated with Antimicrobial Resistance. Clinical Microbiology Reviews, 31(4).
- Pagano, M., Martins, A. F., & Barth, A. L. (2016). Mobile genetic elements related to carbapenem resistance in Acinetobacter baumannii. Brazilian Journal of Microbiology : [Publication of the Brazilian Society for Microbiology], 47(4), 785–792.
- Tang, B., Wang, C., Sun, D., Lin, H., Ma, J., Guo, H., Yang, H., & Li, X. (2022). In Silico Characterization of blaNDM-Harboring Conjugative Plasmids in Acinetobacter Species. Microbiology Spectrum, 10(6).
- Vijayakumar, S., Jacob, J. J., Vasudevan, K., Mathur, P., Ray, P., Neeravi, A., Baskaran, A., Kirubananthan, A., Anandan, S., Biswas, I., Walia, K., & Veeraraghavan, B. (2022). Genomic Characterization of Mobile Genetic Elements Associated With Carbapenem Resistance of Acinetobacter baumannii From India. Frontiers in Microbiology, 13.
- Bi, D., Xie, R., Zheng, J., Yang, H., Zhu, X., Ou, H. Y., & Wei, Q. (2019). Large-Scale Identification of AbaR-Type Genomic Islands in Acinetobacter baumannii Reveals Diverse Insertion Sites and Clonal Lineage-Specific Antimicrobial Resistance Gene Profiles. Antimicrobial Agents and Chemotherapy, 63(4).
- Haddaway, N. R., Page, M. J., Pritchard, C. C., & McGuinness, L. A. (2022). PRISMA2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis. Campbell Systematic Reviews, 18(2).
- Castanheira, M., Mendes, R. E., & Gales, A. C. (2023). Global Epidemiology and Mechanisms of Resistance of Acinetobacter baumannii-calcoaceticus Complex. Clinical Infectious Diseases, 76
- Moubareck, C. A., & Halat, D. H. (2020). Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen. Antibiotics 2020, Vol. 9, Page 119, 9(3), 119.
- Vázquez-López, R., Solano-Gálvez, S. G., Juárez Vignon-Whaley, J. J., Abello Vaamonde, J. A., Padró Alonzo, L. A., Rivera Reséndiz, A., Muleiro Álvarez, M., Vega López, E. N., Franyuti-Kelly, G., Álvarez-Hernández, D. A., Moncaleano Guzmán, V., Juárez Bañuelos, J. E., Marcos Felix, J., González Barrios, J. A., & Barrientos Fortes, T. (2020). Acinetobacter baumannii Resistance: A Real Challenge for Clinicians. Antibiotics (Basel, Switzerland), 9(4), 205.
- Gupta, N., Angadi, K., & Jadhav, S. (2022). Molecular Characterization of Carbapenem-Resistant Acinetobacter baumannii with Special Reference to Carbapenemases: A Systematic Review. Infection and Drug Resistance, 15, 7631–7650.
- Müller, C., Reuter, S., Wille, J., Xanthopoulou, K., Stefanik, D., Grundmann, H., Higgins, P. G., & Seifert, H. (2023). A global view on carbapenem-resistant Acinetobacter baumannii. MBio, 14(6).
- Aurilio, C., Sansone, P., Barbarisi, M., Pota, V., Giaccari, L. G., Coppolino, F., Barbarisi, A., Passavanti, M. B., & Pace, M. C. (2022). Mechanisms of Action of Carbapenem Resistance. Antibiotics, 11(3).
- Beig, M., Badmasti, F., Solgi, H., Nikbin, V. S., & Sholeh, M. (2023). Carbapenemase genes distribution in clonal lineages of Acinetobacter baumannii: a comprehensive study on plasmids and chromosomes. Frontiers in Cellular and Infection Microbiology, 13, 1283583.
- Urban-Chmiel, R., Marek, A., Stępień-Pyśniak, D., Wieczorek, K., Dec, M., Nowaczek, A., & Osek, J. (2022). Antibiotic Resistance in Bacteria-A Review. Antibiotics (Basel, Switzerland), 11(8), 1079.
- Khedkar, S., Smyshlyaev, G., Letunic, I., Maistrenko, O. M., Coelho, L. P., Orakov, A., Forslund, S. K., Hildebrand, F., Luetge, M., Schmidt, T. S. B., Barabas, O., & Bork, P. (2022). Landscape of mobile genetic elements and their antibiotic resistance cargo in prokaryotic genomes. Nucleic Acids Research, 50(6), 3155–3168.
- Brovedan, M. A., Cameranesi, M. M., Limansky, A. S., Morán-Barrio, J., Marchiaro, P., & Repizo, G. D. (2020). What do we know about plasmids carried by members of the Acinetobacter genus? World Journal of Microbiology and Biotechnology 2020 36:8, 36(8), 1–15.
- Sánchez-Urtaza, S., Ocampo-Sosa, A., Rodríguez-Grande, J., El-Kholy, M. A., Shawky, S. M., Alkorta, I., & Gallego, L. (2024). Plasmid content of carbapenem resistant Acinetobacter baumannii isolates belonging to five International Clones collected from hospitals of Alexandria, Egypt. Frontiers in Cellular and Infection Microbiology, 13.
- Barbu, I., Chifiriuc, M., & Popa, L. (2018). MOBILE GENETIC ELEMENTS INVOLVED IN THE HORIZONTAL TRANSFER OF ANTIBIOTIC RESISTANCE GENES. Roumanian Archives of Microbiology and Immunology, 263–276.
- Jeon, J. H., Jang, K. M., Lee, J. H., Kang, L. W., & Lee, S. H. (2023). Transmission of antibiotic resistance genes through mobile genetic elements in Acinetobacter baumannii and gene-transfer prevention. The Science of the Total Environment, 857(Pt 2).
- Salgado-Camargo, A. D., Castro-Jaimes, S., Gutierrez-Rios, R. M., Lozano, L. F., Altamirano-Pacheco, L., Silva-Sanchez, J., Pérez-Oseguera, Á., Volkow, P., Castillo-Ramírez, S., & Cevallos, M. A. (2020). Structure and Evolution of Acinetobacter baumannii Plasmids. Frontiers in Microbiology, 11.
- Lam, M. M. C., Koong, J., Holt, K. E., Hall, R. M., & Hamidian, M. (2023). Detection and Typing of Plasmids in Acinetobacter baumannii Using rep Genes Encoding Replication Initiation Proteins. Microbiology Spectrum, 11(1).
- Blackwell, G. A., & Hall, R. M. (2019). Mobilisation of a small Acinetobacter plasmid carrying an oriT transfer origin by conjugative RepAci6 plasmids. Plasmid, 103, 36–44.
- Ramirez, M. S., Bonomo, R. A., & Tolmasky, M. E. (2020). Carbapenemases: Transforming Acinetobacter baumannii into a Yet More Dangerous Menace. Biomolecules, 10(5).
- Hashemizadeh, Z., Hatam, G., Fathi, J., Aminazadeh, F., Hosseini-Nave, H., Hadadi, M., Shakib, N. H., Kholdiv, S., & Bazargani, A. (2022). The Spread of Insertion Sequences Element and Transposons in Carbapenem Resistant Acinetobacter baumannii in a Hospital Setting in Southwestern Iran. Infection & Chemotherapy, 54(2).
- Lipszyc, A., Szuplewska, M., & Bartosik, D. (2022). How Do Transposable Elements Activate Expression of Transcriptionally Silent Antibiotic Resistance Genes? International Journal of Molecular Sciences, 23(15).
- Zhao, Y., Hu, K., Zhang, J., Guo, Y., Fan, X., Wang, Y., Mensal, S. D., & Zhang, X. (2019). Outbreak of carbapenem-resistant Acinetobacter baumannii carrying the carbapenemase OXA-23 in ICU of the eastern Heilongjiang Province, China. BMC Infectious Diseases, 19(1).
- Vijayakumar, S., Anandan, S., MS, D. P., Kanthan, K., Vijayabaskar, S., Kapil, A., Ray, P., Sistla, S., Bhattacharya, S., Wattal, C., Thirunarayan, Deotale, V., Mathur, P., Walia, K., Ohri, V. C., & Veeraraghavan, B. (2020). Insertion sequences and sequence types profile of clinical isolates of carbapenem-resistant A. baumannii collected across India over four year period. Journal of Infection and Public Health, 13(7), 1022–1028.
- Gaiarsa, S., Bitar, I., Comandatore, F., Corbella, M., Piazza, A., Scaltriti, E., Villa, L., Postiglione, U., Marone, P., Nucleo, E., Pongolini, S., Migliavacca, R., & Sassera, D. (2019). Can Insertion Sequences Proliferation Influence Genomic Plasticity? Comparative Analysis of Acinetobacter baumannii Sequence Type 78, a Persistent Clone in Italian Hospitals. Frontiers in Microbiology, 10.
- Baleivanualala, S. C., Matanitobua, S., Soqo, V., Smita, S., Limaono, J., Sharma, S. C., Devi, S. V., Boseiwaqa, L. V., Vera, N., Kumar, S., Lalibuli, A., Mailulu, J., Wilson, D., Samisoni, Y., Crump, J. A., & Ussher, J. E. (2024). Molecular and clinical epidemiology of carbapenem resistant Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales in Fiji: a multicentre prospective observational study. The Lancet Regional Health. Western Pacific, 47.
- Rao, M., Rashid, F. A., Shukor, S., Hashim, R., & Ahmad, N. (2020). Detection of Antimicrobial Resistance Genes Associated with Carbapenem Resistance from the Whole-Genome Sequence of Acinetobacter baumannii Isolates from Malaysia. The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien Des Maladies Infectieuses et de La Microbiologie Medicale, 2020.
- Salloum, T., Tannous, E., Alousi, S., Arabaghian, H., Rafei, R., Hamze, M., & Tokajian, S. (2018). Genomic mapping of ST85 blaNDM-1 and blaOXA-94 producing Acinetobacter baumannii isolates from Syrian Civil War Victims. International Journal of Infectious Diseases, 74, 100–108.
- Correa, A., Shehreen, S., Machado, L. C., Thesier, J., Cunic, L. M., Petassi, M. T., Chu, J., Kapili, B. J., Jia, Y., England, K. A., & Peters, J. E. (2024). Novel mechanisms of diversity generation in Acinetobacter baumannii resistance islands driven by Tn7-like elements. Nucleic Acids Research, 52(6), 3180–3198.
- Gao, Y., Li, H., Chen, H., Zhang, J., Wang, R., Wang, Z., & Wang, H. (2022). Origin, Phylogeny, and Transmission of the Epidemic Clone ST208 of Carbapenem-Resistant Acinetobacter baumannii on a Global Scale. Microbiology Spectrum, 10(3).
- Acman, M., Wang, R., van Dorp, L., Shaw, L. P., Wang, Q., Luhmann, N., Yin, Y., Sun, S., Chen, H., Wang, H., & Balloux, F. (2022). Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene blaNDM. Nature Communications 2022 13:1, 13(1), 1–13.
- Hamed, S. M., Hussein, A. F. A., Al-Agamy, M. H., Radwan, H. H., & Zafer, M. M. (2022). Tn7382, a novel composite transposon harboring blaNDM-1 and aphA6 in Acinetobacter baumannii. Journal of Global Antimicrobial Resistance, 30, 414–417.
- Mann, R., Rafei, R., Gunawan, C., Harmer, C. J., & Hamidian, M. (2022). Variants of Tn6924, a Novel Tn7 Family Transposon Carrying the blaNDM Metallo-β-Lactamase and 14 Copies of the aphA6 Amikacin Resistance Genes Found in Acinetobacter baumannii. Microbiology Spectrum, 10(1).
- Brito, B. P., Koong, J., Wozniak, A., Opazo-Capurro, A., To, J., Garcia, P., & Hamidian, M. (2022). Genomic Analysis of Carbapenem-Resistant Acinetobacter baumannii Strains Recovered from Chilean Hospitals Reveals Lineages Specific to South America and Multiple Routes for Acquisition of Antibiotic Resistance Genes. Microbiology spectrum, 10(5).
- Sabbagh, P., Rajabnia, M., Maali, A., & Ferdosi-Shahandashti, E. (2021). Integron and its role in antimicrobial resistance: A literature review on some bacterial pathogens. Iranian Journal of Basic Medical Sciences, 24(2), 136–142.
- Bhat, B. A., Mir, R. A., Qadri, H., Dhiman, R., Almilaibary, A., Alkhanani, M., & Mir, M. A. (2023). Integrons in the development of antimicrobial resistance: critical review and perspectives. Frontiers in Microbiology, 14.
- Chakravarty, B. (2020). Genetic mechanisms of antibiotic resistance and virulence in Acinetobacter baumannii: background, challenges and future prospects. Molecular Biology Reports, 47(5), 4037–4046.
- Adeniji, O. O., Elsheikh, E. A. E., & Okoh, A. I. (2022). Prevalence of classes 1 and 2 integrons in multidrug-resistant Acinetobacter baumanni isolates recovered from some aquatic environment in South Africa. Scientific Reports, 12(1).
- Nikibakhsh, M., Firoozeh, F., Badmasti, F., Kabir, K., & Zibaei, M. (2021). Molecular study of metallo-β-lactamases and integrons in Acinetobacter baumannii isolates from burn patients. BMC Infectious Diseases, 21(1.
- Halaji, M., Rezaei, A., Zalipoor, M., & Faghri, J. (2018). Investigation of Class I, II, and III Integrons Among Acinetobacter Baumannii Isolates from Hospitalized Patients in Isfahan, Iran. Oman Medical Journal, 33(1), 37–42.
- Vijayakumar, S., Wattal, C., J.K., O., Bhattacharya, S., Vasudevan, K., Anandan, S., Walia, K., & Veeraraghavan, B. (2020). Insights into the complete genomes of carbapenem-resistant Acinetobacter baumannii harbouring bla OXA-23, bla OXA-420 and bla NDM-1 genes using a hybrid-assembly approach. Access Microbiology, 2(8).
- Hamed, S. M., Hussein, A. F. A., Al-Agamy, M. H., Radwan, H. H., & Zafer, M. M. (2022a). Genetic Configuration of Genomic Resistance Islands in Acinetobacter baumannii Clinical Isolates From Egypt. Frontiers in Microbiology, 13, 878912.
- AP, C., Y, C., TH, C., LM, B., RC, W., MR, J., RA, B., MD, A., & DE, F. (2020). AbGRI4, a novel antibiotic resistance island in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates. The Journal of Antimicrobial Chemotherapy, 75(10).
- Tuffet, R., Carvalho, G., Godeux, A. S., Mazzamurro, F., Rocha, E. P. C., Laaberki, M. H., Venner, S., & Charpentier, X. (2024). Manipulation of natural transformation by AbaR-type islands promotes fixation of antibiotic resistance in Acinetobacter baumannii. Proceedings of the National Academy of Sciences of the United States of America, 121(39)
- Godeux, A. S., Svedholm, E., Barreto, S., Potron, A., Venner, S., Charpentier, X., & Laaberki, M. H. (2022). Interbacterial Transfer of Carbapenem Resistance and Large Antibiotic Resistance Islands by Natural Transformation in Pathogenic Acinetobacter. MBio, 13(1).
- Bi, D., Zheng, J., Xie, R., Zhu, Y., Wei, R., Ou, H.-Y., Wei, Q., & Qin, H. (2020). Comparative Analysis of AbaR-Type Genomic Islands Reveals Distinct Patterns of Genetic Features in Elements with Different Backbones. MSphere, 5(3).
- Khongfak, S., Thummeepak, R., Leungtongkam, U., Tasanapak, K., Thanwisai, A., & Sitthisak, S. (2022). Insights into mobile genetic elements and the role of conjugative plasmid in transferring aminoglycoside resistance in extensively drug-resistant Acinetobacter baumannii AB329. PeerJ, 10.
- Douraghi, M., Kenyon, J. J., Aris, P., Asadian, M., Ghourchian, S., & Hamidian, M. (2020). Accumulation of Antibiotic Resistance Genes in Carbapenem-Resistant Acinetobacter baumannii Isolates Belonging to Lineage 2, Global Clone 1, from Outbreaks in 2012-2013 at a Tehran Burns Hospital. MSphere, 5(2).
- Moreira da Silva, J., Menezes, J., Fernandes, L., Marques, C., Costa, S. S., Timofte, D., Amaral, A., & Pomba, C. (2024). Dynamics of blaOXA-23 gene transmission in Acinetobacter spp. from contaminated veterinary environmental surfaces: an emerging One Health threat? Journal of Hospital Infection, 146, 116–124.
- Huang, Z. Y., Li, J., Shui, J., Wang, H. C., Hu, Y. M., Zou, M. X., & Guo, L. S. (2019). Co-existence of blaOXA-23 and blaVIM in carbapenem-resistant Acinetobacter baumannii isolates belonging to global complex 2 in a Chinese teaching hospital. Chinese Medical Journal, 132(10), 1166.
- Wang, Z., Li, H., Zhang, J., & Wang, H. (2021). Co-Occurrence of blaOXA-23 in the Chromosome and Plasmid: Increased Fitness in Carbapenem-Resistant Acinetobacter baumannii. Antibiotics (Basel, Switzerland), 10(10), 1196.
- Alam, M. Z. (2021). Molecular Characterization of Integrons and Their Association with Antibiotic Resistance in Acinetobacter baumannii Isolated from Hospitals in Jeddah. Applied Biochemistry and Microbiology, 57(1), S64–S70.
- Vrancianu, C. O., Pelcaru, C. F., Alistar, A., Gheorghe, I., Marutescu, L., Popa, M., ... & Chifiriuc, M. C. (2021). Escaping from ESKAPE. Clinical significance and antibiotic resistance mechanisms in acinetobacter baumannii: a review. Biointerface Res Appl Chem, 11(1), 8190-8203.
- Vijayakumar, S., Biswas, I., & Veeraraghavan, B. (2019). Accurate identification of clinically important Acinetobacter spp.: an update. Future science OA, 5(6).
- Strateva, T. V., Sirakov, I., Stoeva, T. J., Stratev, A., & Peykov, S. (2023). Phenotypic and Molecular Characteristics of Carbapenem-Resistant Acinetobacter baumannii Isolates from Bulgarian Intensive Care Unit Patients. Microorganisms, 11(4).