PHYLOGENETIC ANALYSIS OF THE EVOLUTIONARY STABILITY OF THE icaA GENE WITHIN THE GLOBAL STAPHYLOCOCCUS AUREUS POPULATION

Authors

  • N.Ya KRAVETS Horbachevsky Ternopil National Medical University Author
  • M.V. SHEVCHENKO Bila Tserkva National Agrarian University Author
  • T. M. TSARENKO Horbachevsky Ternopil National Medical University Author

DOI:

https://doi.org/10.31861/biosystems2025.02.216

Keywords:

Staphylococcus aureus, tonsillitis, icaA, biofilm, phylogenetic analysis, Maximum Likelihood, conservatism

Abstract

Staphylococcus aureus is one of the most significant opportunistic pathogens affecting humans and animals. A key factor in its virulence is its ability to form biofilms, which is mediated by the biosynthesis of the polysaccharide intercellular adhesin and encoded by the icaA gene. However, the evolutionary dynamics and degree of conservatism of this gene within the global S. aureus population are not well understood. This study aimed to elucidate evolutionary relationships and assess genetic diversity of the icaA gene among different S. aureus isolates. Twenty-three nucleotide sequences, representative of 14 countries and various ecological niches (clinical, veterinary and environmental), isolated between 2004 and 2025, were analysed. Phylogenetic analysis of the icaA gene (using the maximum likelihood method MEGA 12, GTR+G model) confirmed its conservatism, as all isolates studied formed a dense cluster with short branches, indicating low nucleotide divergence. A main cluster was identified that united isolates from Europe and North America. This cluster has been circulating for over 20 years, indicating the global spread of clones with a stable icaA sequence. The analysis showed that isolates of animal origin from Pakistan did not form a statistically significant subclade, suggesting an absence of local adaptation of the icaA gene in these populations. While some strains from Asia show minor local divergence, the overall tree structure highlights the gene's high stability. The results confirm that the icaA gene is a highly conserved functional gene subject to strong negative selective pressure due to its critical function. This gene's stability may be pivotal to S. aureus' success as a global pathogen.

References

1. Abbas, A. A. R., & Hamim, S. S. (2020). Phylogenetic profile of Staphylococcus aureus mecA and icaA genes associated with UTI patients. Indian Journal of Public Health Research and Development, 11(2), 1169–1176. Available from: https://www.researchgate.net/publication/338134319_Phylogenetic_Profile_of_Staphylococcus_aureus_mec_A_and_ica_A_genes_Associated_with_UTI_Patients

2. Andersen, C., Greve, T., Reinholdt, K. B., et al. (2023). Bacterial findings in patients referred to hospital for the treatment of acute tonsillitis with or without peritonsillar phlegmon. BMC Infectious Diseases, 23(1), 439. https://doi.org/10.1186/s12879-023-08420-8

3. Azarian, T., Cella, E., Baines, S. L., Shumaker, M. J., Samel, C., Jubair, M., Pegues, D. A., & David, M. Z. (2021). Genomic Epidemiology and Global Population Structure of Exfoliative Toxin A-Producing Staphylococcus aureus Strains Associated With Staphylococcal Scalded Skin Syndrome. Frontiers in Microbiology, 12, 663831. https://doi.org/10.3389/fmicb.2021.663831

4. Beenken, K. E., Dunman, P. M., McAleese, F., Macapagal, D., Murphy, E., Projan, S. J., Blevins, J. S., & Smeltzer, M. S. (2004). Global gene expression in Staphylococcus aureus biofilms. Journal of Bacteriology, 186(14), 4665–4684. https://doi.org/10.1128/JB.186.14.4665-4684.2004.

5. Brook, I. (2005). The role of anaerobic bacteria in tonsillitis. International Journal of Pediatric Otorhinolaryngology, 69(1), 9–19. https://doi.org/10.1016/j.ijporl.2004.08.007

6. Hall, C. W., & Mah, T. F. (2017). Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiology Reviews, 41(3), 276–301. https://doi.org/10.1093/femsre/fux010

7. Hammoudi, A. A., & Mohammed, N. S. (2025). Molecular characteristic of Staphylococcus aureus isolated from patients with nasal carriage infections. Regulatory Mechanisms in Biosystems, 16(3), e25157. https://doi.org/10.15421/0225157

8. Klagisa, R., Racenis, K., Broks, R., Balode, A. O., Kise, L., & Kroica, J. (2022). Analysis of microorganism colonization, biofilm production, and antibacterial susceptibility in recurrent tonsillitis and peritonsillar abscess patients. International Journal of Molecular Sciences, 23(18), 10783. https://doi.org/10.3390/ijms231810783

9. Kravets, N. Y., Klumnyk, S. I., Romanyuk, L. B., & Borak, V. P. (2022). Biofilm-forming properties of pathogenic microorganisms in children with recurrent tonsillitis. World of Medicine and Biology, 80(2), 210–213. https://doi.org/10.26724/2079-8334-2022-2-80-210-213

10. Kumar, S., Stecher, G., Li, M., Knyaz, C., & Tamura, K. (2018). MEGA X: Molecular Evolutionary Genetics Analysis across Desktop, Cloud and Web. Molecular Biology and Evolution, 35(6), 1547–1549. https://doi.org/10.1093/molbev/msy096.

11. Miller, J. M., Binnicker, M. J., Campbell, S., Carroll, K. C., Chapin, K. C., Gonzalez, M. D., & Yao, J. D. (2024). Guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2024 update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). Clinical Infectious Diseases. https://pubmed.ncbi.nlm.nih.gov/

12. Nimmana BK, & Paterek E. (2025). Tonsillitis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544342/

13. Pallon, J., Rööst, M., Sundqvist, M., & Hedin, K. (2021). The aetiology of pharyngotonsillitis in primary health care: A prospective observational study. BMC Infectious Diseases, 21(1), 971. https://doi.org/10.1186/s12879-021-06665-9

14. Peng, Q., Tang, X., Dong, W., Sun, N., & Yuan, W. (2022). A review of biofilm formation of Staphylococcus aureus and its regulation mechanism. Antibiotics, 12(1), 12. https://doi.org/10.3390/antibiotics12010012

15. Pizauro, L. J. L., de Almeida, C. C., Silva, S. R., et al. (2021). Genomic comparisons and phylogenetic analysis of mastitis-related staphylococci with a focus on adhesion, biofilm, and related regulatory genes. Scientific Reports, 11(1), 17392. https://doi.org/10.1038/s41598-021-96842-2

16. Silva-de-Jesus, A. C., Ferrari, R. G., Panzenhagen, P., dos Santos, A. M. P., Portes, A. B., & Conte-Junior, C. A. (2025). Distribution of antimicrobial resistance and biofilm production genes in the genomic sequences of S. aureus: a global in silico analysis. Antibiotics, 14(4), 364. https://doi.org/10.3390/antibiotics14040364

17. Suzuki, H., Lefébure, T., Bitar, P. P., & Stanhope, M. J. (2012). Comparative genomic analysis of the genus Staphylococcus including Staphylococcus aureus and its newly described sister species Staphylococcus simiae. BMC Genomics, 13(1), 38. https://doi.org/10.1186/1471-2164-13-38.

18. Volch, I., Mykhailyshyn, H., Kravets, N., Pyatkovskyy, T., & Bukata, V. (2025). Biofilm formation and antibiotic resistance of clinical isolates from diabetic foot ulcers. Bulletin of Medical and Biological Research, 7(3), 46-53. https://doi.org/10.63341/bmbr/3.2025.46

19. Woo, J. H., Kim, S. T., Kang, I. G., Lee, J. H., Cha, H. E., & Kim, D. Y. (2012). Comparison of tonsillar biofilms between patients with recurrent tonsillitis and a control group. Acta Oto-Laryngologica, 132(11), 1115–1120. https://doi.org/10.3109/00016489.2012.692541

20. Zautner, A. E., Krause, M., Stropahl, G., Holtfreter, S., Frickmann, H., Maletzki, C., Kreikemeyer, B., Pau, W. H., & Podbielski, A. (2010). Intracellular persisting Staphylococcus aureus is the major pathogen in recurrent tonsillitis. PLoS ONE, 5(3), e9452. https://doi.org/10.1371/journal.pone.0009452

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Published

2025-12-23

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БІОХІМІЯ, БІОТЕХНОЛОГІЯ, МОЛЕКУЛЯРНА ГЕНЕТИКА