Preview

Antibiot Khimioter = Antibiotics and Chemotherapy

Advanced search

Comparative Analysis of Phenotypic and Genetic Resistance of Pseudomonas aeruginosa Clinical Isolates to Antimicrobial Drugs

https://doi.org/10.37489/0235-2990-2025-70-3-4-23-31

EDN: HWLNFO

Abstract

Background. The World Health Organization has included Pseudomonas aeruginosa in the list of multidrug-resistant bacteria which urgently requires the development of new antibiotics and regulation of the use of existing ones. The aim of the study was to identify and evaluate the correlation of phenotypic and genetic resistance of clinical isolates of P. aeruginosa isolated from patients in the Republic of Tatarstan. Methods. 40 clinical isolates of P. aeruginosa from patients in the Republic of Tatarstan were studied. Susceptibility to antimicrobial drugs was assessed using the disk diffusion method. The presence of resistance genes was tested using polymerase chain reaction. Results. Phenotypic resistance to beta-lactam antibiotics was detected in 85–100% of clinical isolates of P. aeruginosa out of 40 studied. Moreover, 38% of isolates carried the mexB gene for resistance to beta-lactam antibiotics. Resistance to fluoroquinolones was shown by 80% of isolates, and resistance to aminoglycosides was detected in 45–55%. The mexD gene associated with resistance to fluoroquinolones was identified in 20% of isolates. The aminoglycoside resistance genes (mexY, aac(3)-IIa, aphA1, rpsL) were detected in 3–50% of P. aeruginosa isolates, respectively. Conclusion. The presented results indicate a discrepancy between the phenotypic manifestation of resistance and the presence of antibiotic resistance genes. This indicates the presence of many mechanisms of resistance to the same groups of antibiotics, which should be taken into account when developing complex drugs to overcome bacterial resistance to the drug. At the same time, isolates with a low level of expression of genetic resistance determinants are susceptible to the antibiotic and pose a threat of spreading resistance genes.

About the Authors

L. L. Yadykova
Kazan (Volga Region) Federal University
Russian Federation

Liudmila L. Yadykova — laboratory assistant-researcher

Kazan


Competing Interests:

Авторы заявляют об отсутствии конфликта интересов по представленной статье.



L. T. Bayazitova Lira T.,
Kazan Scientific Research Institute of Epidemiology and Microbiology
Russian Federation

Lira T. Bayazitova — Ph. D. in Medicine, professor, head of the microbiology laboratory

Kazan


Competing Interests:

Авторы заявляют об отсутствии конфликта интересов по представленной статье.



S. A. Lisovskaya
Kazan Scientific Research Institute of Epidemiology and Microbiology; Kazan State Medical University
Russian Federation

Svetlana A. Lisovskaya — Ph. D. in Biology, leading researcher

Kazan


Competing Interests:

Авторы заявляют об отсутствии конфликта интересов по представленной статье.



E. Yu. Trizna
Kazan (Volga Region) Federal University
Russian Federation

Elena Yu. Trizna — Ph. D. in Biology, Senior Researcher

Kazan


Competing Interests:

Авторы заявляют об отсутствии конфликта интересов по представленной статье.



References

1. Pang Z., Raudonis R., Glick B. R., Lin T. J., Cheng Z. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnol Adv. 2019; 37 (1): 177–192. doi: 10.1016/j.biotechadv.2018.11.013.

2. Ma Y. X., Wang C. Y., Li YY, Li J, Wan Q. Q., Chen J. H., Tay F. R., Niu L. N. Considerations and caveats in combating ESKAPE pathogens against nosocomial infections. Advanced Science. 2020; 7 (1): 1901872. doi: 10.1002/advs.201901872.

3. Davies J., Davies D. Origins and evolution of antibiotic resistance. Microbiology and molecular biology reviews. 2010; 74 (3): 417–433. doi: 10.1128/mmbr.00016-10.

4. Gow S. P., Waldner C. L., Harel J., Boerlin P. Associations between antimicrobial resistance genes in fecal generic escherichia coli isolates from cow-calf herds in Western Canada. Appl Environ Microbiol.2008; 74 (12): 3658–3666. doi: 10.1128/AEM.02505-07.

5. Ullah W., Qasim M., Rahman H., Jie Y., Muhammad N. Beta-lactamaseproducing Pseudomonas aeruginosa: Phenotypic characteristics and molecular identification of virulence genes. J Chin Med Assoc. 2017; 80 (3): 173–177. doi: 10.1016/j.jcma.2016.08.011.

6. Avakh A., Grant G. D., Cheesman M. J., Kalkundri T., Hall S. The art of war with Pseudomonas aeruginosa: targeting mex efflux pumps directly to strategically enhance antipseudomonal drug efficacy. Antibiotics (Basel). 2023; 12 (8): 1304. doi: 10.3390/antibiotics12081304.

7. Idris F. N., Nadzir M. M. Multi-drug resistant ESKAPE pathogens and the uses of plants as their antimicrobial agents. Archf Microbiol. 2023; 205 (4): 115. doi: 10.1007/s00203-023-03455-6.

8. Lee J. H., Kim N. H., Jang K. M., Jin H., Shin K., Jeong B. C., Kim D. W., Lee S. H. Prioritization of critical factors for surveillance of the dissemination of antibiotic resistance in Pseudomonas aeruginosa: a systematic review. Int J Mol Sci. 2023; 24 (20): 15209. doi: 10.3390/ijms242015209.

9. Lorusso A. B., Carrara J. A., Barroso C. D. N., Tuon F. F., Faoro H. Role of efflux pumps on antimicrobial resistance in Pseudomonas aeruginosa. Int J Mol Sci. 2022; 23 (24): 15779. doi: 10.3390/ijms232415779.

10. Zahedi Bialvaei A., Rahbar M., Hamidi-Farahani R., Asgari A., Esmailkhani A., Mardani Dashti Y., Soleiman-Meigooni S. Expression of RND efflux pumps mediated antibiotic resistance in Pseudomonas aeruginosa clinical strains. Microb Pathog. 2021; 153: 104789. doi: 10.1016/j.micpath.2021.104789.

11. Ramirez M. S., Tolmasky M. E. Aminoglycoside modifying enzymes. Drug resistance updates. 2010; 13 (6): 151–171. doi: 10.1016/j.drup.2010.08.003.

12. Cox G., Stogios P. J., Savchenko A., Wright G. D. Structural and molecular basis for resistance to aminoglycoside antibiotics by the adenylyltransferase ANT (2″)-Ia. MBio. 2015; 6 (1): 10–1128. doi: 10.1128/mBio.02180-14.

13. Berrazeg M., Jeannot K., Ntsogo Enguene V. Y., Broutin I., Loeffert S., Fournier D., Plesiat P. Mutations in β-lactamase AmpC increase resistance of Pseudomonas aeruginosa isolates to antipseudomonal cephalosporins. Antimicrob Agents Chemother. 2015; 59 (10): 6248–6255. doi: 10.1128/AAC.00825-15.

14. Blair J. M., Webber M. A., Baylay A. J., Ogbolu D. O., Piddock L. J. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol. 2015; 13 (1): 42–51. doi: 10.1038/nrmicro3380.

15. Yoneda K., Chikumi H., Murata T., Gotoh N., Yamamoto H., Fujiwara H., Nishini T., Shimizu E. Measurement of Pseudomonas aeruginosa multidrug efflux pumps by quantitative real-time polymerase chain reaction. FEMS Microbiol Lett. 2005; 243 (1): 125–131. doi: 10.1016/j.femsle.2004.11.048.

16. Xavier D. E., Picao R. C., Girardello R., Fehlberg L. C., Gales A. C. Efflux pumps expression and its association with porin down-regulation and beta-lactamase production among Pseudomonas aeruginosa causing bloodstream infections in Brazil. BMC Microbiol. 2010; 10: 217. doi: 10.1186/1471-2180-10-217.

17. Saenz Y., Brinas L., Domínguez E., Ruiz J., Zarazaga M., Vila J., Torres C. Mechanisms of resistance in multiple-antibiotic-resistant Escherichia coli strains of human, animal, and food origins. Antimicrob Agents Chemother. 2004; 48 (10): 3996–4001. doi: 10.1128/AAC.48.10.3996-4001.2004.

18. Maynard C., Fairbrother J. M., Bekal S., Sanschagrin F., Levesque R. C., Brousseau R., Masson L., Lariviere S., Harel J. Antimicrobial resistance genes in enterotoxigenic Escherichia coli O149: K91 isolates obtained over a 23-year period from pigs. Antimicrob Agents Chemother. 2003; 47 (10): 3214–3221. doi: 10.1128/AAC.47.10.3214-3221.2003.

19. Diaz P. Q., Bello H. T., Dominguez M. Y., Trabal N. F., Mella S. M., Zemelman R. Z., Gonzalez G. R. Díaz P. Q., Bello H. T., Domínguez M. Y., Trabal N. F., Mella S. M., Zemelman R. Z., Gonzalez G. R. Resistencia a gentamicina, amikacina y ciprofloxacina en cepas hospitalarias de Klebsiella pneumoniae subespecie pneumoniae productoras de beta-lactamasas. Rev Med Chil. 2004; 132 (10): 1173–1178. doi: 10.4067/s0034- 98872004001000003.

20. Dumas J., Delden C., Perron K., Köhler T. Analysis of antibiotic resistance gene expression in Pseudomonas aeruginosa by quantitative real-time- PCR. FEMS Microbiol Lett. 2006; 254 (2): 217–225. doi: 10.1111/j.1574- 6968.2005.00008.x.

21. Orazi G., O'Toole G. A. «It Takes a Village»: mechanisms underlying antimicrobial recalcitrance of polymicrobial biofilms. J Bacteriol. 2019; 202 (1): e00530–19. Published 2019 Dec 6. doi: 10.1128/JB.00530-19.

22. Dreier J., Ruggerone P. Interaction of antibacterial compounds with RND efflux pumps in Pseudomonas aeruginosa. Front Microbiol. 2015; 6: 660. doi: 10.3389/fmicb.2015.00660.

23. Pourakbari B., Yaslianifard S., Yaslianifard S., Mahmoudi S., KeshavarzValian S., Mamishi S. Evaluation of efflux pumps gene expression in resistant Pseudomonas aeruginosa isolates in an Iranian referral hospital. Iran J Microbiol. 2016; 8 (4): 249–256.

24. Arjomandzadegan M., Gravand S. Analysis of rpsL and rrs genes mutations related to streptomycin resistance in Mdr and Xdr clinical isolates of Mycobacterium tuberculosis. Tuberk Toraks. 2015; 63 (4): 235–242. doi: 10.5578/tt.6474.

25. Jacoby G. A. AmpC β-lactamases. Clinical microbiology reviews. 2009; 22 (1): 161–182. doi: 10.1128/CMR.00036-08.

26. Tamma P. D., Doi Y., Bonomo R. A., Johnson J. K., Simner P. J.; Antibacterial Resistance Leadership Group. A primer on AmpC β-lactamases: necessary knowledge for an increasingly multidrug-resistant world. Clin Infect Dis. 2019; 69 (8): 1446–1455. doi: 10.1093/cid/ciz173.

27. Philippon A., Arlet G., Jacoby G. A. Plasmid-determined AmpC-type beta-lactamases. Antimicrob Agents Chemother. 2002; 46 (1): 1–11. doi: 10.1128/AAC.46.1.1-11.2002.

28. Kotova V. Y., Ryzhenkova K. V., Manukhov I. V., Zavilgelsky G. B. Inducible specific lux-biosensors for the detection of antibiotics: Construction and main parameters. Appl Biochem Microbiol. 2014; 50: 98–103. doi: 10.1134/S0003683814010074.


Review

For citations:


Yadykova L.L., Bayazitova Lira T., L.T., Lisovskaya S.A., Trizna E.Yu. Comparative Analysis of Phenotypic and Genetic Resistance of Pseudomonas aeruginosa Clinical Isolates to Antimicrobial Drugs. Antibiot Khimioter = Antibiotics and Chemotherapy. 2025;70(3-4):23-31. https://doi.org/10.37489/0235-2990-2025-70-3-4-23-31. EDN: HWLNFO

Views: 13


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 0235-2990 (Print)