abkBA toxin–antitoxin system may act as antipersister modules in Acinetobacter baumannii clinical isolates
Abstract
Aim: Persistence cells comprise a subpopulation of bacteria that is resistant to treatment. In this study, the role of the toxin–antitoxin (TA) system in the formation of persistence cells of Acinetobacter baumannii isolates was investigated. Methods: After confirming all isolates, TA systems abkBA, mqsRA and higBA were identified. Persister cells were confirmed using the standard method. Real-time PCR was used to compare the expression of TA systems in isolates in persistence and normal states. Results: The abkAB system was present in all isolates; 4% of isolates formed persister cells. The expression level of the abkB gene in persistent isolates showed a sevenfold increase compared with nonpersistent isolates. Conclusion: The abkBA system is proposed as an antipersistence target in A. baumannii isolates.
Plain language summary
Although antibiotics remain the easiest and best way to treat infectious diseases, due to their inappropriate use, the occurrence of drug-resistant infections is an important health challenge. For this reason, finding ways to control infectious diseases without antibiotics is a necessity. One way that this can be done is to target systems within the bacteria, like the recently discovered toxin–antitoxin system, which can be considered a future target for the treatment of resistant infectious diseases.
Tweetable abstract
The abkBA toxin–antitoxin system is likely involved in the persistence phenotype in clinical isolates of Acinetobacter baumannii.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. . Biology of Acinetobacter baumannii: pathogenesis, antibiotic resistance mechanisms, and prospective treatment options. Front. Cell Infect. 7(55), 1–35 (2017). • A comprehensive study investigating the characteristics and importance of Acinetobacter baumannii.
- 2. . Acinetobacter baumannii: evolution of a global pathogen. Foodborne Pathog. Dis. 71(3), 292–301 (2014).
- 3. . Global epidemiology of colistin resistant Acinetobacter baumannii. J. Infect. Dis. Ther. 4, 287–292 (2016).
- 4. . Acinetobacter baumannii: biology and drug resistance–role of carbapenemases. Folia Histochem. Cytobiol. 54(2), 61–74 (2016).
- 5. . Acinetobacter baumannii antibiotic resistance mechanisms. Pathogens 10(3), 373–404 (2021).
- 6. . Persister cells. Annu. Rev. Microbiol. 64, 357–372 (2010). • Describes the history of persister cells and their importance.
- 7. . Bacterial persisters and infection: past, present, and progressing. Annu. Rev. Microbiol. 73, 359–385 (2019). • Investigating the relationship between persister cells and antibiotic persistence and the role of persister cells in the development of infectious diseases.
- 8. . Stress responses linked to antimicrobial resistance in Acinetobacter species. Appl. Microbiol. Biotechnol. 104, 1423–1435 (2020). • Investigating the role of cellular processes such as toxin–antitoxin systems in antibiotic resistance.
- 9. Clinical and Laboratory Standards Institute M100 32nd Edition–Performance Standards for Antimicrobial Susceptibility Testing. Clinical and Laboratory Standards Institute, PA, USA (2022).
- 10. . Curcumin alleviates persistence of Acinetobacter baumannii against colistin. Sci. Rep. 8(1), 11029 (2018). • A study on the assay of persister cells against colistin treatment in Acinetobacter baumannii strains.
- 11. . Novel protocol for persister cells isolation. PLOS ONE 9(2), e88660 (2014). •• Using enzymatic lysis as a new method to detect persister cells.
- 12. . Analysis of relative gene expression data using real-time quantitative PCR and the 2– ΔΔCT method. Methods 25(4), 402–408 (2001).
- 13. The relationship between phoH and colistin-heteroresistant in clinical isolates of Acinetobacter baumannii. Gene Rep. 25, 101356–101362 (2021).
- 14. . Multidrug tolerance of biofilms and persister cells. Bacterial Biofilms 1(1), 107–131 (2008).
- 15. Characterization of plasmids carrying the bla OXA-24/40 carbapenemase gene and the genes encoding the AbkA/AbkB proteins of a toxin/antitoxin system. J. Antimicrob. Chemother. 69(10), 2629–2633 (2014). • Investigating the possible role of the AbkA/AbkB system in antibiotic resistance of Acinetobacter baumannii strains.
- 16. . Acinetobacter baumannii antibiotic resistance mechanisms. Pathogens 10(3), 373 (2021).
- 17. . Prevalence of multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in an Italian hospital. J. Infect. Public Health 6(3), 179–185 (2013).
- 18. . Colistin resistance in Acinetobacter baumannii isolated from critically ill patients: clinical characteristics, antimicrobial susceptibility and outcome. Afr. Health Sci. 19(3), 2400–2406 (2019).
- 19. Characterization and transcriptome analysis of Acinetobacter baumannii persister cells. Microb. Drug Resist. 24(10), 1466–1474 (2018). • Discusses the role of toxin–antitoxin systems in the formation of persister cells.
- 20. MqsR/MqsA toxin/antitoxin system regulates persistence and biofilm formation in Pseudomonas putida KT2440. Front. Microbiol. 8, 840 (2017).
- 21. . Persister cells formation and expression of type II toxin–antitoxin system genes in Brucella melitensis (16M) and Brucella abortus (B19). Iran J. Pathol. 15(2), 127–133 (2020).
