Evaluation of the relationship between quorum sensing system genes and antibiotic resistance in isolated Pseudomonas aeruginosa from cystic fibrosis patients
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Abstract
Background and Objectives: Pseudomonas aeruginosa is a Gram-negative bacterium that causes respiratory infections in individuals with cystic fibrosis. Its level of virulence is primarily controlled through Quorum Sensing (QS), a communication mechanism that utilizes small signaling molecules. This study investigates P. aeruginosa antibiotic resistance in CF patients in Imam Khomeini Hospital and examines the presence of QS genes in resistant strains.
Materials and Methods: Sixty-five P. aeruginosa samples were identified in CF patients in Imam Khomeini Hospital in Tehran. Antibiotic resistance was assessed using the disk diffusion method, and QS genes (rhlI, rhlR, lasI, lasR) were evaluated by applying PCR.
Results: Approximately 61.5 % of P. aeruginosa strains were multiple-drug-resistant (MDR), with 30.7% classified as extensively drug-resistant (XDR). The highest resistance was observed against amoxicillin, amikacin, and cefepime. The most common QS gene in MDR and XDR strains was rhlR. Additionally, 78.9% of XDR isolates carried rhlI, rhlR, lasI, and lasR genes.
Conclusion: The study specified that more than half of the P. aeruginosa strains exhibited resistance to five antibiotic classes, and effective antibiotics against P. aeruginosa were colistin, meropenem, ciprofloxacin, piperacillin/tazobactam, and cefotaxime. A noteworthy correlation was identified between MDR and XDR strains and the existence of QS genes in the strains.
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2. AbdulWahab A, Zahraldin K, Sid Ahmed MA, Jarir SA, Muneer M, Mohamed SF, et al. The emergence of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis patients on inhaled antibiotics. Lung India 2017; 34: 527-531.
3. Soto-Aceves MP, Cocotl-Yañez M, Servín-González L, Soberón-Chávez G. The Rhl quorum-sensing system is at the top of the regulatory hierarchy under phosphate-limiting conditions in Pseudomonas aeruginosa PAO1. J Bacteriol 2021; 203(5): e00475-20.
4. Campoccia D, Montanaro L, Arciola CR. A review of the clinical implications of anti-infective biomaterials and infection-resistant surfaces. Biomaterials 2013; 34: 8018-8029.
5. Abidi SH, Sherwani SK, Siddiqui TR, Bashir A, Kazmi SU. Drug resistance profile and biofilm forming potential of Pseudomonas aeruginosa isolated from contact lenses in Karachi-Pakistan. BMC Ophthalmol 2013; 13: 57.
6. Farajzadeh Sheikh A, Moradi Bandbal M, Saki M. Emergence of multidrug-resistant Shigella species harboring extended-spectrum beta-lactamase genes in pediatric patients with diarrhea from southwest of Iran. Mol Biol Rep 2020; 47: 7097-7106.
7. O’Connor K, Zhao CY, Mei M, Diggle SP. Frequency of quorum-sensing mutations in Pseudomonas aeruginosa strains isolated from different environments. Microbiology (Reading) 2022; 168: 001265.
8. Tuon FF, Dantas LR, Suss PH, Tasca Ribeiro VS. Pathogenesis of the Pseudomonas aeruginosa biofilm: a review. Pathogens 2022; 11: 300.
9. Lima JLDC, Alves LR, Jacomé PRLA, Bezerra Neto JP, Maciel MAV, Morais MMC. Biofilm production by clinical isolates of Pseudomonas aeruginosa and structural changes in LasR protein of isolates non biofilm-producing. Braz J Infect Dis 2018; 22: 129-136.
10. Dolatshah L, Tabatabaei M. A phenotypic and molecular investigation of biofilm formation in clinical samples of Pseudomonas aeruginosa. Mol Biol Res Commun 2021; 10: 157-163.
11. Aboushleib HM, Omar HM, Abozahra R, Elsheredy A, Baraka K. Correlation of quorum sensing and virulence factors in Pseudomonas aeruginosa isolates in Egypt. J Infect Dev Ctries 2015; 9: 1091-1099.
12. Alayande AB, Aung MM, Kim IS. Correlation between quorum sensing signal molecules and Pseudomonas aeruginosa’s biofilm development and virulency. Curr Microbiol 2018; 75: 787-793.
13. Pachori P, Gothalwal R, Gandhi P. Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; a critical review. Genes Dis 2019; 6: 109-119.
14. Papa R, Imperlini E, Trecca M, Paris I, Vrenna G, Artini M, et al. Virulence of Pseudomonas aeruginosa in cystic fibrosis: Relationships between normoxia and anoxia lifestyle. Antibiotics (Basel) 2023; 13: 1.
15. Cruz RL, Asfahl KL, Van den Bossche S, Coenye T, Crabbé A, Dandekar AA. RhlR-regulated acyl-homoserine lactone quorum sensing in a cystic fibrosis isolate of Pseudomonas aeruginosa. mBio 2020; 11(2): e00532-20.
16. Levinson W (2008). Review of medical microbiology and immunology. McGraw Hill/Medical.
17. Sands KM, Twigg JA, Lewis MAO, Wise MP, Marchesi JR, Smith A, et al. Microbial profiling of dental plaque from mechanically ventilated patients. J Med Microbiol 2016; 65: 147-159.
18. CLSI (2023). Performance Standards for Antimicrobial Susceptibility Testing. 33rd ed. CLSI supplement M100. Clinical and Laboratory Standards Institute, USA.
19. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18: 268-281.
20. Saderi H, Owlia P. Detection of multidrug resistant (MDR) and extremely drug resistant (XDR) P. aeruginosa isolated from patients in Tehran, Iran. Iran J Pathol 2015; 10: 265-271.
21. Hemmati J, Nazari M, Abolhasani FS, Ahmadi A, Asghari B. In vitro investigation of relationship between quorum-sensing system genes, biofilm forming ability, and drug resistance in clinical isolates of Pseudomonas aeruginosa. BMC Microbiol 2024; 24: 99.
22. Singh VK, Almpani M, Wheeler KM, Rahme LG. Interconnections of Pseudomonas aeruginosa quorum-sensing systems in intestinal permeability and inflammation. mBio 2023; 14(2): e0352422.
23. Pang Z, Raudonis R, Glick BR, Lin T-J, Cheng Z. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnol Adv 2019; 37: 177-192.
24. Stoner SN, Baty JJ, Scoffield JA. Pseudomonas aeruginosa polysaccharide Psl supports airway microbial community development. ISME J 2022; 16: 1730-1739.
25. Rajabi H, Salimizand H, Khodabandehloo M, Fayyazi A, Ramazanzadeh R. Prevalence of algD, pslD, pelF, Ppgl, and PAPI-1 genes involved in rabiofilm formation in clinical Pseudomonas aeruginosa strains. Biomed Res Int 2022; 2022: 1716087.
26. Bonyadi P, Saleh NT, Dehghani M, Yamini M, Amini K. Prevalence of antibiotic resistance of Pseudomonas aeruginosa in cystic fibrosis infection: a systematic review and meta-analysis. Microb Pathog 2022; 165: 105461.
27. Lucca F, Guarnieri M, Ros M, Muffato G, Rigoli R, Da Dalt L. Antibiotic resistance evolution of Pseudomonas aeruginosa in cystic fibrosis patients (2010‐2013). Clin Respir J 2018; 12: 2189-2196.
28. Emaneini M, Kalantar-Neyestanaki D, Jabalameli L, Hashemi M, Beigverdi R, Jabalameli F. Molecular analysis and antimicrobial resistance pattern of distinct strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients in Iran. Iran J Microbiol 2019; 11: 98-107.
29. Jarzynka S, Makarewicz O, Weiss D, Minkiewicz-Zochniak A, Iwańska A, Skorupa W, et al. The Impact of Pseudomonas aeruginosa Infection in Adult Cystic Fibrosis Patients-A Single Polish Centre Study. Pathogens 2023; 12: 1440.
30. Groleau MC, Taillefer H, Vincent AT, Constant P, Déziel E. Pseudomonas aeruginosa isolates defective in function of the LasR quorum sensing regulator are frequent in diverse environmental niches. Environ Microbiol 2022; 24: 1062-1075.
31. Jeske A, Arce-Rodriguez A, Thöming JG, Tomasch J, Häussler S. Evolution of biofilm-adapted gene expression profiles in lasR-deficient clinical Pseudomonas aeruginosa isolates. NPJ Biofilms Microbiomes 2022; 8: 6.
32. Perez LR, Machado AB, Barth AL. The presence of quorum-sensing genes in Pseudomonas isolates infecting cystic fibrosis and non-cystic fibrosis patients. Curr Microbiol 2013; 66: 418-420.
2. AbdulWahab A, Zahraldin K, Sid Ahmed MA, Jarir SA, Muneer M, Mohamed SF, et al. The emergence of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis patients on inhaled antibiotics. Lung India 2017; 34: 527-531.
3. Soto-Aceves MP, Cocotl-Yañez M, Servín-González L, Soberón-Chávez G. The Rhl quorum-sensing system is at the top of the regulatory hierarchy under phosphate-limiting conditions in Pseudomonas aeruginosa PAO1. J Bacteriol 2021; 203(5): e00475-20.
4. Campoccia D, Montanaro L, Arciola CR. A review of the clinical implications of anti-infective biomaterials and infection-resistant surfaces. Biomaterials 2013; 34: 8018-8029.
5. Abidi SH, Sherwani SK, Siddiqui TR, Bashir A, Kazmi SU. Drug resistance profile and biofilm forming potential of Pseudomonas aeruginosa isolated from contact lenses in Karachi-Pakistan. BMC Ophthalmol 2013; 13: 57.
6. Farajzadeh Sheikh A, Moradi Bandbal M, Saki M. Emergence of multidrug-resistant Shigella species harboring extended-spectrum beta-lactamase genes in pediatric patients with diarrhea from southwest of Iran. Mol Biol Rep 2020; 47: 7097-7106.
7. O’Connor K, Zhao CY, Mei M, Diggle SP. Frequency of quorum-sensing mutations in Pseudomonas aeruginosa strains isolated from different environments. Microbiology (Reading) 2022; 168: 001265.
8. Tuon FF, Dantas LR, Suss PH, Tasca Ribeiro VS. Pathogenesis of the Pseudomonas aeruginosa biofilm: a review. Pathogens 2022; 11: 300.
9. Lima JLDC, Alves LR, Jacomé PRLA, Bezerra Neto JP, Maciel MAV, Morais MMC. Biofilm production by clinical isolates of Pseudomonas aeruginosa and structural changes in LasR protein of isolates non biofilm-producing. Braz J Infect Dis 2018; 22: 129-136.
10. Dolatshah L, Tabatabaei M. A phenotypic and molecular investigation of biofilm formation in clinical samples of Pseudomonas aeruginosa. Mol Biol Res Commun 2021; 10: 157-163.
11. Aboushleib HM, Omar HM, Abozahra R, Elsheredy A, Baraka K. Correlation of quorum sensing and virulence factors in Pseudomonas aeruginosa isolates in Egypt. J Infect Dev Ctries 2015; 9: 1091-1099.
12. Alayande AB, Aung MM, Kim IS. Correlation between quorum sensing signal molecules and Pseudomonas aeruginosa’s biofilm development and virulency. Curr Microbiol 2018; 75: 787-793.
13. Pachori P, Gothalwal R, Gandhi P. Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; a critical review. Genes Dis 2019; 6: 109-119.
14. Papa R, Imperlini E, Trecca M, Paris I, Vrenna G, Artini M, et al. Virulence of Pseudomonas aeruginosa in cystic fibrosis: Relationships between normoxia and anoxia lifestyle. Antibiotics (Basel) 2023; 13: 1.
15. Cruz RL, Asfahl KL, Van den Bossche S, Coenye T, Crabbé A, Dandekar AA. RhlR-regulated acyl-homoserine lactone quorum sensing in a cystic fibrosis isolate of Pseudomonas aeruginosa. mBio 2020; 11(2): e00532-20.
16. Levinson W (2008). Review of medical microbiology and immunology. McGraw Hill/Medical.
17. Sands KM, Twigg JA, Lewis MAO, Wise MP, Marchesi JR, Smith A, et al. Microbial profiling of dental plaque from mechanically ventilated patients. J Med Microbiol 2016; 65: 147-159.
18. CLSI (2023). Performance Standards for Antimicrobial Susceptibility Testing. 33rd ed. CLSI supplement M100. Clinical and Laboratory Standards Institute, USA.
19. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18: 268-281.
20. Saderi H, Owlia P. Detection of multidrug resistant (MDR) and extremely drug resistant (XDR) P. aeruginosa isolated from patients in Tehran, Iran. Iran J Pathol 2015; 10: 265-271.
21. Hemmati J, Nazari M, Abolhasani FS, Ahmadi A, Asghari B. In vitro investigation of relationship between quorum-sensing system genes, biofilm forming ability, and drug resistance in clinical isolates of Pseudomonas aeruginosa. BMC Microbiol 2024; 24: 99.
22. Singh VK, Almpani M, Wheeler KM, Rahme LG. Interconnections of Pseudomonas aeruginosa quorum-sensing systems in intestinal permeability and inflammation. mBio 2023; 14(2): e0352422.
23. Pang Z, Raudonis R, Glick BR, Lin T-J, Cheng Z. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnol Adv 2019; 37: 177-192.
24. Stoner SN, Baty JJ, Scoffield JA. Pseudomonas aeruginosa polysaccharide Psl supports airway microbial community development. ISME J 2022; 16: 1730-1739.
25. Rajabi H, Salimizand H, Khodabandehloo M, Fayyazi A, Ramazanzadeh R. Prevalence of algD, pslD, pelF, Ppgl, and PAPI-1 genes involved in rabiofilm formation in clinical Pseudomonas aeruginosa strains. Biomed Res Int 2022; 2022: 1716087.
26. Bonyadi P, Saleh NT, Dehghani M, Yamini M, Amini K. Prevalence of antibiotic resistance of Pseudomonas aeruginosa in cystic fibrosis infection: a systematic review and meta-analysis. Microb Pathog 2022; 165: 105461.
27. Lucca F, Guarnieri M, Ros M, Muffato G, Rigoli R, Da Dalt L. Antibiotic resistance evolution of Pseudomonas aeruginosa in cystic fibrosis patients (2010‐2013). Clin Respir J 2018; 12: 2189-2196.
28. Emaneini M, Kalantar-Neyestanaki D, Jabalameli L, Hashemi M, Beigverdi R, Jabalameli F. Molecular analysis and antimicrobial resistance pattern of distinct strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients in Iran. Iran J Microbiol 2019; 11: 98-107.
29. Jarzynka S, Makarewicz O, Weiss D, Minkiewicz-Zochniak A, Iwańska A, Skorupa W, et al. The Impact of Pseudomonas aeruginosa Infection in Adult Cystic Fibrosis Patients-A Single Polish Centre Study. Pathogens 2023; 12: 1440.
30. Groleau MC, Taillefer H, Vincent AT, Constant P, Déziel E. Pseudomonas aeruginosa isolates defective in function of the LasR quorum sensing regulator are frequent in diverse environmental niches. Environ Microbiol 2022; 24: 1062-1075.
31. Jeske A, Arce-Rodriguez A, Thöming JG, Tomasch J, Häussler S. Evolution of biofilm-adapted gene expression profiles in lasR-deficient clinical Pseudomonas aeruginosa isolates. NPJ Biofilms Microbiomes 2022; 8: 6.
32. Perez LR, Machado AB, Barth AL. The presence of quorum-sensing genes in Pseudomonas isolates infecting cystic fibrosis and non-cystic fibrosis patients. Curr Microbiol 2013; 66: 418-420.
| Files | ||
| Issue | Vol 17 No 5 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i5.19886 | |
| Keywords | ||
| Pseudomonas aeruginosa Cystic fibrosis Drug resistance Quorum sensing | ||
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How to Cite
1.
Ehsani A, Soleimani N, Modaresi Estehbanati M. Evaluation of the relationship between quorum sensing system genes and antibiotic resistance in isolated Pseudomonas aeruginosa from cystic fibrosis patients. Iran J Microbiol. 2025;17(5):773-782.
