Antimicrobial resistance of Klebsiella pneumoniae strains isolated from COVID-19 patients: genetic analysis and phenotypic characterization

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Abstract

Introduction. Klebsiella pneumoniae is one of the most significant opportunistic pathogens, causing a wide range of infections in hospitalized patients and characterized by a high capacity to accumulate antimicrobial resistance genes.

Aim: analysis of the phenotypic resistance profile to antimicrobials and molecular characteristics (resistance and virulence genes) in clinical К. pneumoniae strains isolated from COVID-19 patients, and a comparative assessment of the relationship between the studied genetic and phenotypic traits.

Materials and methods. A total of 102 COVID-19 patients were examined. Nasopharyngeal swabs were analyzed using classical bacteriological methods. Phenotypic antimicrobial susceptibility testing was conducted using the disk-diffusion method. Whole-genome sequencing was performed on 9 K. pneumoniae isolates, followed by bioinformatics analysis of genetic profiles for antimicrobial resistance (AMR) and virulence.

Results. The analysis revealed that the predominant resistance mechanism in the studied K. pneumoniae strains was antimicrobial inactivation (42.4%), highlighting the significance of enzymatic inactivation as a primary resistance mechanism. A substantial proportion of genetic determinants were associated with efflux pumps (36.3%), indicating their role in conferring resistance to a broad spectrum of antimicrobials. Smaller fractions of genes were linked to target modification (9.1%), target protection (6.1%), and reduced permeability (6.1%); however, their coexistence suggests a multifactorial AMR profile in K. pneumoniae. Phenotypically, all strains exhibited resistance to at least two antimicrobials, with 67% of isolates resistant to all tested agents. Comparative analysis of virulence factor genes and AMR determinants revealed statistically significant differences (p < 0.001). Correlation analysis demonstrated a statistically significant inverse correlation (p = 0.034) between these two parameters.

Conclusions. The phenotypic susceptibility of K. pneumoniae to antimicrobials, despite the presence of resistance genes, may result from the complex interplay of regulatory mechanisms, genetic element stability, and environmental conditions. The findings suggest a pronounced trend toward reduced prevalence of virulence factor genes with increasing AMR gene abundance.

About the authors

Guzel Sh. Isaeva

Kazan State Medical University

Author for correspondence.
Email: guisaeva@rambler.ru
ORCID iD: 0000-0002-1462-8734

Dr. Sci. (Med.), Head, Department of microbiology named after Academician V.M. Aristovsky

Russian Federation, Kazan

Nikita S. Chumarev

Kazan State Medical University

Email: nikitasergeevichsno@gmail.com
ORCID iD: 0000-0001-6247-6184

postgraduate student, Department of microbiology named after Academician V.M. Aristovsky

Russian Federation, Kazan

Marina N. Belova

Republican Clinical Infectious Diseases Hospital named after Professor A.F. Agafonov

Email: belova.marina@tatar.ru
ORCID iD: 0000-0001-9579-3370

Head, Bacteriological laboratory

Russian Federation, Kazan

Natalya D. Shaykhrazieva

City Clinical Hospital No. 7, Kazan

Email: epid-gkb7@mail.ru
ORCID iD: 0000-0002-2241-3100

Cand. Sci. (Med.), epidemiologist, Head, Epidemiological department

Russian Federation, Kazan

References

  1. Dong N., Yang X., Chan E.W., et al. Klebsiella species: Taxonomy, hypervirulence and multidrug resistance. EBioMedicine. 2022;79:103998. DOI: https://doi.org/10.1016/j.ebiom.2022.103998
  2. Wyres K.L., Holt K.E. Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria. Curr. Opin. Microbiol. 2018;45:131–9. DOI: https://doi.org/10.1016/j.mib.2018.04.004
  3. Vuotto C., Longo F., Pascolini C., et al. Biofilm formation and antibiotic resistance in Klebsiella pneumoniae urinary strains. J. Appl. Microbiol. 2017;123(4):1003–18. DOI: https://doi.org/10.1111/jam.13533
  4. Чеботарь И.В., Кулешов К.В. Между антибиотикорезистентностью и вирулентностью: диалектика бактериального фитнеса. Клиническая микробиология и антимикробная химиотерапия. 2024;26(1):4–17. Chebotar I.V., Kuleshov K.V. Antibiotic resistance vs. Virulence in the context of bacterial fitness dialectics. Clinical Microbiology and Antimicrobial Chemotherapy. 2024;26(1):4–17. DOI: https://doi.org/10.36488/cmac.2024.1.59-66 EDN: https://elibrary.ru/bromnk
  5. Чеботарь И.В., Бочарова Ю.А., Подопригора И.В., Шагин А.В. Геномный анализ вирулентности и антибиотикорезистентности Klebsiella pneumoniae. Современные методы анализа микробиологических сообществ. 2020;22(1):4–19. Chebotar' I.V., Bocharova Yu.A., Podoprigora I.V., Shagin A.V. The reasons why Klebsiella pneumoniae becomes a leading opportunistic pathogen. Clinical Microbiology and Antimicrobial Chemotherapy. 2020;22(1):4–19. DOI: https://doi.org/10.36488/cmac.2020.1.4-19
  6. Ghosh S., Bornman C., Zafer M.M., et al. Antimicrobial resistance threats in the emerging COVID-19 pandemic: Where do we stand? J. Infect. Public Health. 2021;14(5):555–60. DOI: https://doi.org/10.1016/j.jiph.2021.02.011
  7. Adebisi Y.A., Alaran A.J., Okereke M., et al. COVID-19 and antimicrobial resistance: a review. Infect. Dis. (Auckl). 2021;14:11786337211033870. DOI: https://doi.org/10.1177/11786337211033870
  8. Российские рекомендации. Определение чувствительности микроорганизмов к антимикробным препаратам. Версия 2024-02. Смоленск;2024. Russian Guidelines. Determination of Microorganism Susceptibility to Antimicrobial Agents. Version 2024-02. Smolensk;2024.
  9. Nishino K., Yamaguchi A. Role of histone-like protein H-NS in multidrug resistance of Escherichia coli. J. Bacteriol. 2004;186(5):1423–9. DOI: https://doi.org/10.1128/JB.186.5.1423-1429.2004
  10. Sedrakyan A., Gevorgyan Z., Zakharyan M., et al. Molecular epidemiology and in-depth characterization of Klebsiella pneumoniae clinical isolates from Armenia. Int. J. Mol. Sci. 2025;26(2):504. DOI: https://doi.org/10.3390/ijms26020504
  11. Li J., Zhang H., Ning J., et al. The nature and epidemiology of OqxAB, a multidrug efflux pump. Antimicrob. Resist. Infect. Control. 2019;8:44. DOI: https://doi.org/10.1186/s13756-019-0489-3
  12. Zeng L., Zhang J., Li C., et al. The determination of gyrA and parC mutations and the prevalence of plasmid-mediated quinolone resistance genes in carbapenem resistant Klebsiella pneumonia ST11 and ST76 strains isolated from patients in Heilongjiang Province. China Infect. Genet. Evol. 2020;82:104319. DOI: https://doi.org/10.1016/j.meegid.2020.104319
  13. Martin R.M., Bachman M.A. Colonization, infection, and the accessory genome of Klebsiella pneumoniae. Front. Cell. Infect. Microbiol. 2018;8:4. DOI: https://doi.org/10.3389/fcimb.2018.00004
  14. Yang, J. Exploring multidrug-resistant Klebsiella pneumoniae antimicrobial resistance mechanisms through whole genome sequencing analysis. BMC Microbiology. 2023;23(1):245. DOI: https://doi.org/10.1186/s12866-023-02974-y
  15. Oliveira R., Castro J., Silva S., et al. Exploring the antibiotic resistance profile of clinical Klebsiella pneumoniae isolates in Portugal. Antibiotics (Basel). 2022;11(11):1613. DOI: https://doi.org/10.3390/antibiotics11111613

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Copyright (c) 2025 Isaeva G.S., Chumarev N.S., Belova M.N., Shaykhrazieva N.D.

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