year 17, Issue 1 (January - February 2023)                   Iran J Med Microbiol 2023, 17(1): 90-102 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Shayea R H, Ali M R. Whole-genome Study of Carbapenem-resistant Acinetobacter baumannii Virulence and Resistance. Iran J Med Microbiol 2023; 17 (1) :90-102
1- Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq ,
2- Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq
Abstract:   (901 Views)

Background and Aim: Carbapenem-resistant Acinetobacter baumannii (CRAb) has ability to develop and acquire resistance makes it one of the most critical nosocomial pathogens globally. Whole genome sequemcing (WGS) technology was employed to map genes associated with antimicrobial resistance (AMR),virulene factors and to identify multilocus sequence types (MLST). In order to understand the resistance mechanism for A. baumannii species, this study set out to establish the genetic makeup of the species.
Materials and Methods: Whole-genome sequencing (WGS) of A.b4, A.b49 and A.b75 was performed using Illumina MiSeq and the genomes were assembled with SPAdes. ARG-ANNOT, CARD-RGI, VFDB, PHAST, PlasmidFinder were used to analyse all genomes.
Results: Genome analysis revealed that Ab4 belongs to ST944, represented singletons that could not be attributed to any, A.b49 belongs to ST1104, represented unique ST.While A.b75 belongs to ST195 which represented known international clones of high risk .Molecular characterisation showed the presence 23 antibiotic resistance genes in all straines of A. baumannii. 12 of them are shared by all 3 strains and 11 are common between A. baumannii 4(ST/944), 49 (ST/1104) and 75(ST/195). The common drug-resistance genes shared by all 3 strains include bla OXA-72 (resistance to carbapenems), ade genes, RND (adeFJKadeLN adeR), and SMR   (abeS) encoding for efflux pumps.
Conclusion: We present WGS analysis of three A. baumannii strains belonging to three different STs. The presence of strains harboring acquired AMR genes makes them more dangerous. Acquired resistance genes and chromosomal gene mutation are successful routes for disseminating AMR determinants among A. baumannii. Identification of chromosomal and plasmid-encoded AMR in the genome of A. baumannii may help understand the mechanism behind the genetic mobilization and spread of AMR genes.

Full-Text [PDF 746 kb]   (310 Downloads) |   |   Full-Text (HTML)  (355 Views)  
Type of Study: Original Research Article | Subject: Molecular Microbiology
Received: 2022/07/21 | Accepted: 2022/09/9 | ePublished: 2023/01/20

1. Santajit S, Indrawattana N. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens. Biomed Res Int. 2016;2016:2475067. [DOI:10.1155/2016/2475067] [PMID] [PMCID]
2. Kurihara MNL, Sales ROd, Silva KEd, Maciel WG, Simionatto S. Multidrug-resistant Acinetobacter baumannii outbreaks: a global problem in healthcare settings. Rev Soc Bras Med Trop. 2020;53. [DOI:10.1590/0037-8682-0248-2020] [PMID] [PMCID]
3. Ayobami O, Willrich N, Harder T, Okeke IN, Eckmanns T, Markwart R. The incidence and prevalence of hospital-acquired (carbapenem-resistant) Acinetobacter baumannii in Europe, Eastern Mediterranean and Africa: a systematic review and meta-analysis. Emerg Microbes Infect. 2019;8(1):1747-59. [DOI:10.1080/22221751.2019.1698273] [PMID] [PMCID]
4. Wareth G, Linde J, Hammer P, Nguyen NH, Nguyen TNM, Splettstoesser WD, et al. Phenotypic and WGS-derived antimicrobial resistance profiles of clinical and non-clinical Acinetobacter baumannii isolates from Germany and Vietnam. Int J Antimicrob Agents. 2020;56(4):106127. [DOI:10.1016/j.ijantimicag.2020.106127] [PMID]
5. Brovedan MA, Cameranesi MM, Limansky AS, Morán-Barrio J, Marchiaro P, Repizo GD. What do we know about plasmids carried by members of the Acinetobacter genus? World J Microbiol Biotechnol. 2020;36(8):109. [DOI:10.1007/s11274-020-02890-7] [PMID]
6. Pagano M, Martins AF, Barth AL. Mobile genetic elements related to carbapenem resistance in Acinetobacter baumannii. Braz J Microbiol. 2016;47:785-92. [DOI:10.1016/j.bjm.2016.06.005] [PMID] [PMCID]
7. Brandt C, Braun SD, Stein C, Slickers P, Ehricht R, Pletz MW, et al. In silico serine β-lactamases analysis reveals a huge potential resistome in environmental and pathogenic species. Sci Rep. 2017;7(1):43232. [DOI:10.1038/srep43232] [PMID] [PMCID]
8. Quainoo S, Coolen Jordy PM, van Hijum Sacha AFT, Huynen Martijn A, Melchers Willem JG, van Schaik W, et al. Whole-Genome Sequencing of Bacterial Pathogens: the Future of Nosocomial Outbreak Analysis. Clin Microbiol Rev. 2017;30(4):1015-63. [DOI:10.1128/CMR.00016-17] [PMID] [PMCID]
9. Durand G, Javerliat F, Bes M, Veyrieras J-B, Guigon G, Mugnier N, et al. Routine Whole-Genome Sequencing for Outbreak Investigations of Staphylococcus aureus in a National Reference Center. Front Microbiol. 2018;9. [DOI:10.3389/fmicb.2018.00511] [PMID] [PMCID]
10. Lin MF, Lan CY. Antimicrobial resistance in Acinetobacter baumannii: From bench to bedside. World J Clin Cases. 2014;2(12):787-814. [DOI:10.12998/wjcc.v2.i12.787] [PMID] [PMCID]
11. Atlas RM, Brown AE, Parks LC. Laboratory Manual of Experimental Microbiology: Mosby, st. Louis U.S.A; 1997.
12. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing, CLSI supplement M100 CLSI. 30th ed: Wayne, PA; 2020.
13. Abed E, Ali M. Molecular Analysis of Efflux Pumps and Quorum Sensing Genes In Mdr Acinetobacter Baumannii. Biochem Cell Arch. 2020;20(1):0-000.
14. Ridha D, Ali M, Jassim K. Occurrence of Metallo-β-Lactamase Genes among Acinetobacter Baumannii Isolated from Different Clinical Samples. J Pure Appl Microbiol. 2019;13(2):1111-9. [DOI:10.22207/JPAM.13.2.50]
15. Turton JF, Gabriel SN, Valderrey C, Kaufrnann ME, Pitt TL. Use of sequence-based typing and multiplex PCR to identify clonal lineages of outbreak strains of Acinetobacter baumannii. Clin Microbiol Infect. 2007;13(8):807-15. [DOI:10.1111/j.1469-0691.2007.01759.x] [PMID]
16. Coudron Philip E, Moland Ellen S, Thomson Kenneth S. Occurrence and Detection of AmpC Beta-Lactamases among Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis Isolates at a Veterans Medical Center. J Clin Microbiol. 2000;38(5):1791-6. [DOI:10.1128/JCM.38.5.1791-1796.2000] [PMID] [PMCID]
17. García-Soto S, Abdel-Glil MY, Tomaso H, Linde J, Methner U. Emergence of Multidrug-Resistant Salmonella enterica Subspecies enterica Serovar Infantis of Multilocus Sequence Type 2283 in German Broiler Farms. Front Microbiol. 2020;11. [DOI:10.3389/fmicb.2020.01741] [PMID] [PMCID]
18. Andrews S. FastQC: A Quality Control Tool for High Throughput Sequence Data. v. 0.11.5. 2020.
19. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M, Kulikov AS, et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol. 2012;19(5):455-77. [DOI:10.1089/cmb.2012.0021] [PMID] [PMCID]
20. Gurevich A, Saveliev V, Vyahhi N, G T. QUAST: Quality assessment tool for genome assemblies. Bioinformatics. 2013;29:1072-5. [DOI:10.1093/bioinformatics/btt086] [PMID] [PMCID]
21. Wood DE, Lu J, Langmead B. Improved metagenomic analysis with Kraken 2. Genome Biol. 2019;20(1):257. [DOI:10.1186/s13059-019-1891-0] [PMID] [PMCID]
22. Feldgarden M, Brover V, Haft Daniel H, Prasad Arjun B, Slotta Douglas J, Tolstoy I, et al. Validating the AMRFinder Tool and Resistance Gene Database by Using Antimicrobial Resistance Genotype-Phenotype Correlations in a Collection of Isolates. Antimicrob Agents Chemother. 2019;63(11):e00483-19. [DOI:10.1128/AAC.00483-19] [PMID] [PMCID]
23. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S, Lund O, et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother. 2012;67(11):2640-4. [DOI:10.1093/jac/dks261] [PMID] [PMCID]
24. Jia B, Raphenya AR, Alcock B, Waglechner N, Guo P, Tsang KK, et al. CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database. Nucleic Acids Res. 2017;45(D1):D566-D73. [DOI:10.1093/nar/gkw1004] [PMID] [PMCID]
25. Liu B, Zheng D, Jin Q, Chen L, Yang J. VFDB 2019: a comparative pathogenomic platform with an interactive web interface. Nucleic Acids Res. 2019;47(D1):D687-D92. [DOI:10.1093/nar/gky1080] [PMID] [PMCID]
26. Lowe TM, Eddy SR. tRNAscan-SE: A Program for Improved Detection of Transfer RNA Genes in Genomic Sequence. Nucleic Acids Res. 1997;25(5):955-64. [DOI:10.1093/nar/25.5.955] [PMID] [PMCID]
27. Lagesen K, Hallin P, Rødland EA, Staerfeldt HH, Rognes T, Ussery DW. RNAmmer: consistent and rapid annotation of ribosomal RNA genes. Nucleic Acids Res. 2007;35(9):3100-8. [DOI:10.1093/nar/gkm160] [PMID] [PMCID]
28. Gao F, Zhang C-T. GC-Profile: a web-based tool for visualizing and analyzing the variation of GC content in genomic sequences. Nucleic Acids Res. 2006;34(suppl_2):W686-W91. [DOI:10.1093/nar/gkl040] [PMID] [PMCID]
29. Arndt D, Grant JR, Marcu A, Sajed T, Pon A, Liang Y, et al. PHASTER: a better, faster version of the PHAST phage search tool. Nucleic Acids Res. 2016;44(W1):W16-W21. [DOI:10.1093/nar/gkw387] [PMID] [PMCID]
30. Couvin D, Bernheim A, Toffano-Nioche C, Touchon M, Michalik J, Néron B, et al. CRISPRCasFinder, an update of CRISRFinder, includes a portable version, enhanced performance and integrates search for Cas proteins. Nucleic Acids Res. 2018;46(W1):W246-W51. [DOI:10.1093/nar/gky425] [PMID] [PMCID]
31. Carattoli A, Zankari E, García-Fernández A, Voldby Larsen M, Lund O, Villa L, et al. In Silico Detection and Typing of Plasmids using PlasmidFinder and Plasmid Multilocus Sequence Typing. Antimicrob Agents Chemother. 2014;58(7):3895-903. [DOI:10.1128/AAC.02412-14] [PMID] [PMCID]
32. Schwengers O, Barth P, Falgenhauer L, Hain T, Chakraborty T, Goesmann A. Platon: identification and characterization of bacterial plasmid contigs in short-read draft assemblies exploiting protein sequence-based replicon distribution scores. Microb Genom. 2020;6(10). [DOI:10.1099/mgen.0.000398] [PMID] [PMCID]
33. Schramm STJ, Place K, Montaña S, Almuzara M, Fung S, Fernandez JS, et al. Genetic and Phenotypic Features of a Novel Acinetobacter Species, Strain A47, Isolated From the Clinical Setting. Front Microbiol. 2019;10:1375. [DOI:10.3389/fmicb.2019.01375] [PMID] [PMCID]
34. Hamidian M, Nigro SJ. Emergence, molecular mechanisms and global spread of carbapenem-resistant Acinetobacter baumannii. Microb Genom. 2019;5(10). [DOI:10.1099/mgen.0.000306]
35. Thirapanmethee K, Srisiri-a-nun T, Houngsaitong J, Montakantikul P, Khuntayaporn P, Chomnawang MT. Prevalence of OXA-Type β-Lactamase Genes among Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates in Thailand. Antibiotics [Internet]. 2020; 9(12). [DOI:10.3390/antibiotics9120864] [PMID] [PMCID]
36. Tada T, Uchida H, Hishinuma T, Watanabe S, Tohya M, Kuwahara-Arai K, et al. Molecular epidemiology of multidrug-resistant Acinetobacter baumannii isolates from hospitals in Myanmar. J Glob Antimicrob Resist. 2020;22:122-5. [DOI:10.1016/j.jgar.2020.02.011] [PMID]
37. Gaiarsa S, Batisti Biffignandi G, Esposito EP, Castelli M, Jolley KA, Brisse S, et al. Comparative Analysis of the Two Acinetobacter baumannii Multilocus Sequence Typing (MLST) Schemes. Front Microbiol. 2019;10:930. [DOI:10.3389/fmicb.2019.00930] [PMID] [PMCID]
38. Kunin V, Copeland A, Lapidus A, Mavromatis K, Hugenholtz P. A Bioinformatician's Guide to Metagenomics. Microbiol Mol Biol Rev. 2008;72(4):557-78. [DOI:10.1128/MMBR.00009-08] [PMID] [PMCID]
39. Lee SY, Oh MH, Yun SH, Choi CW, Park EC, Song HS, et al. Genomic characterization of extensively drug-resistant Acinetobacter baumannii strain, KAB03 belonging to ST451 from Korea. Infect Genet Evol. 2018;65:150-8. [DOI:10.1016/j.meegid.2018.07.030] [PMID]
40. Jennings LJ, Arcila ME, Corless C, Kamel-Reid S, Lubin IM, Pfeifer J, et al. Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists. J Mol Diagn. 2017;19(3):341-65. [DOI:10.1016/j.jmoldx.2017.01.011] [PMID] [PMCID]
41. Ma X, Shao Y, Tian L, Flasch DA, Mulder HL, Edmonson MN, et al. Analysis of error profiles in deep next-generation sequencing data. Genome Biol. 2019;20(1):50. [DOI:10.1186/s13059-019-1659-6] [PMID] [PMCID]
42. Sims D, Sudbery I, Ilott NE, Heger A, Ponting CP. Sequencing depth and coverage: key considerations in genomic analyses. Nat Rev Genet. 2014;15(2):121-32. [DOI:10.1038/nrg3642] [PMID]
43. Kauser A. Resistome Identification from Whole Genome Sequencing Data of Norwegian Isolates. Norway2020.
44. Roca I, Espinal P, Vila-Farrés X, Vila J. The Acinetobacter baumannii oxymoron: commensal hospital dweller turned pan-drug-resistant menace. Front Microbiol. 2012;3:148. [DOI:10.3389/fmicb.2012.00148] [PMID] [PMCID]
45. Agaras BC, Iriarte A, Valverde CF. Genomic insights into the broad antifungal activity, plant-probiotic properties, and their regulation, in Pseudomonas donghuensis strain SVBP6. PloS one. 2018;13(3):e0194088. [DOI:10.1371/journal.pone.0194088] [PMID] [PMCID]
46. Ten KE, Md Zoqratt MZH, Ayub Q, Tan HS. Characterization of multidrug-resistant Acinetobacter baumannii strain ATCC BAA1605 using whole-genome sequencing. BMC Res Notes. 2021;14(1):83. [DOI:10.1186/s13104-021-05493-z] [PMID] [PMCID]
47. Wright MS, Iovleva A, Jacobs MR, Bonomo RA, Adams MD. Genome dynamics of multidrug-resistant Acinetobacter baumannii during infection and treatment. Genome Med. 2016;8(1):26. [DOI:10.1186/s13073-016-0279-y] [PMID] [PMCID]
48. Rao M, Rashid FA, Shukor S, Hashim R, Ahmad N. Detection of antimicrobial resistance genes associated with carbapenem resistance from the whole-genome sequence of Acinetobacter baumannii isolates from Malaysia. Can J Infect Dis Med Microbiol. 2020;2020. [DOI:10.1155/2020/5021064] [PMID] [PMCID]
49. Khurshid M, Rasool MH, Ashfaq UA, Aslam B, Waseem M, Xu Q, et al. Dissemination of blaOXA-23-harbouring carbapenem-resistant Acinetobacter baumannii clones in Pakistan. J Glob Antimicrob Resist. 2020;21:357-62. [DOI:10.1016/j.jgar.2020.01.001] [PMID]
50. Mortazavi SM, Farshadzadeh Z, Janabadi S, Musavi M, Shahi F, Moradi M, et al. Evaluating the frequency of carbapenem and aminoglycoside resistance genes among clinical isolates of Acinetobacter baumannii from Ahvaz, south-west Iran. New Microbes New Infect. 2020;38:100779. [DOI:10.1016/j.nmni.2020.100779] [PMID] [PMCID]
51. Ostrer L, Khodursky RF, Johnson JR, Hiasa H, Khodursky A. Analysis of mutational patterns in quinolone resistance-determining regions of GyrA and ParC of clinical isolates. Int J Antimicrob Agents. 2019;53(3):318-24. [DOI:10.1016/j.ijantimicag.2018.12.004] [PMID]
52. Leus Inga V, Weeks Jon W, Bonifay V, Smith L, Richardson S, Zgurskaya Helen I. Substrate Specificities and Efflux Efficiencies of RND Efflux Pumps of Acinetobacter baumannii. J Bacteriol. 2018;200(13):e00049-18. [DOI:10.1128/JB.00049-18] [PMID] [PMCID]
53. Coyne S, Courvalin P, Périchon B. Efflux-Mediated Antibiotic Resistance in Acinetobacter spp. Antimicrob Agents Chemother. 2011;55(3):947-53. [DOI:10.1128/AAC.01388-10] [PMID] [PMCID]
54. Sharma A, Sharma R, Bhattacharyya T, Bhando T, Pathania R. Fosfomycin resistance in Acinetobacter baumannii is mediated by efflux through a major facilitator superfamily (MFS) transporter-AbaF. J Antimicrob Chemother. 2017;72(1):68-74. [DOI:10.1093/jac/dkw382] [PMID]
55. Yakkala H, Samantarrai D, Gribskov M, Siddavattam D. Comparative genome analysis reveals niche-specific genome expansion in Acinetobacter baumannii strains. PLoS One. 2019;14(6):e0218204. [DOI:10.1371/journal.pone.0218204] [PMID] [PMCID]
56. Choi CH, Hyun SH, Lee JY, Lee JS, Lee YS, Kim SA, et al. Acinetobacter baumannii outer membrane protein A targets the nucleus and induces cytotoxicity. Cell Microbiol. 2008;10(2):309-19.
57. Tipton Kyle A, Dimitrova D, Rather Philip N. Phase-Variable Control of Multiple Phenotypes in Acinetobacter baumannii Strain AB5075. J Bacteriol. 2015;197(15):2593-9. [DOI:10.1128/JB.00188-15] [PMID] [PMCID]
58. Andersen SB, Ghoul M, Griffin AS, Petersen B, Johansen HK, Molin S. Diversity, prevalence, and longitudinal occurrence of type II toxin-antitoxin systems of Pseudomonas aeruginosa infecting cystic fibrosis lungs. Front Microbiol. 2017;8:1180. [DOI:10.3389/fmicb.2017.01180] [PMID] [PMCID]
59. Bobay L-M, Rocha EPC, Touchon M. The Adaptation of Temperate Bacteriophages to Their Host Genomes. Mol Biol Evol. 2013;30(4):737-51. [DOI:10.1093/molbev/mss279] [PMID] [PMCID]
60. Touchon M, Bernheim A, Rocha EPC. Genetic and life-history traits associated with the distribution of prophages in bacteria. ISME J. 2016;10(11):2744-54. [DOI:10.1038/ismej.2016.47] [PMID] [PMCID]

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2023 CC BY-NC 4.0 | Iranian Journal of Medical Microbiology

Designed & Developed by : Yektaweb | Publisher: Farname Inc