Investigation of the effect of the probiotic bacterium Lactobacillus casei on oprD gene expression in clinical isolates of imipenem-resistant Pseudomonas

Articles in Press

Document Type : Original Article- English

Authors

Department of Microbiology. Fal. C., Islamic Azad University, Isfahan, Iran

10.22108/bjm.2026.147664.1661

Abstract

OprD purine serve as a specific entry channel for drugs such as carbapenems in the outer membrane of Pseudomonas aeruginosa. Probiotics can play a role in inhibiting carbapenems resistance through efflux pumps by regulating the expression of OprD. This study aimed to investigate the effect of Lactobacillus casei on the expression of the oprD gene in clinical isolates of carbapenem-resistant P. aeruginosa. Bacteria were isolated and identified biochemically from clinical samples in Isfahan, and the carbapenem-resistant pattern was studied. The effect of L. casei and its cell-free culture supernatant (CFS) in De Man, Rogosa, and Sharpe (MRS) culture medium was investigated on oprD gene expression in the strains (one-way analysis of variance). A total of 37 P. aeruginosa strains were isolated, of which 54% were obtained from female patients and 46% from male patients. The highest number of strains (29.8%) was isolated from the age group of 21 to 30 years, and the lowest number (5.4%) was isolated from the age group of 51 to 60 years. The majority of strains were isolated from wounds (32.4%), and the lowest number was isolated from blood (19%). All strains produced biofilms, of which 10 (27%), 12 (32.4%), and 12 strains (32.4%) formed weak, moderate, and strong biofilms, respectively. The highest resistance was to the antibiotic imipenem (43.2%). All strains carrying the oprD gene exhibited resistance to the antimicrobial effects of the probiotic L. casei and its supernatant. However, the expression of the oprD gene was 67% and 36% of control after treatment with the probiotic and its CSF, respectively. Given the key role of the OprD porin in antibiotic-resistant strains of P. aeruginosa, inhibition of OprD production by L. casei and its supernatant is of particular preventive and therapeutic importance by controlling resistance to antibiotics in these strains.

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References

  • Fortunato G, Vaz-Moreira I, Gajic I, Manaia CM. Insight into phylogenomic bias of blaVIM-2 or blaNDM-1 dissemination amongst carbapenem-resistant Pseudomonas aeruginosa. International Journal of Antimicrobial Agents. 2023;61(5):106788. https://doi.org/10.1016/j.ijantimicag.2023.106788
  • Sada M, Kimura H, Nagasawa N, Akagawa M, Okayama K, Shirai T, Sunagawa S, Kimura R, Saraya T, Ishii H, Kurai D. Molecular evolution of the Pseudomonas aeruginosa DNA gyrase gyrA gene. 2022;10(8): 1660. https://doi.org/10.3390/microorganisms10081660
  • Li F, Chen D, Li L, Liang D, Wang F, Zhang B. Analysis of metallo-β-lactamases, oprD mutation, and multidrug resistance of β-lactam antibiotic-resistant strains of Pseudomonas aeruginosa isolated from Southern China. Current Microbiology. 2020;77:3264-3269. https://doi.org/10.1007/s00284-020-02148-3
  • Alimoghadam S, Eslami A, Alimoghadam R, Mianrood IB, Looha MA, Khodadadi S, Shokouhi S, Darazam IA. The frequency of AmpC overproduction, OprD downregulation and OprM efflux pump expression in Pseudomonas aeruginosa: A comprehensive meta-analysis. Journal of Global Antimicrobial Resistance. 2024; 39: 159-69. https://doi.org/10.1016/j.jgar.2024.08.014
  • Nguyen T, Brody H, Radaic A, Kapila Probiotics for periodontal health—Current molecular findings. Periodontology. 2000; 87(1): 254-67. https://doi.org/10.1111/prd.12382
  • Hill D, Sugrue I, Tobin C, Hill C, Stanton C, Ross RP. The Lactobacillus casei group: history and health related applications. Frontiers in Microbiology. 2018;9:2107. https://doi.org/10.3389/fmicb.2018.02107
  • Naghavi NS, Rezaeizadeh G, Sarami F, Khayam-Nekooii MS, Khosravi-Darani K. A comparison between different methods for the preservation of lactic acid bacteria for usage as a starter culture. Journal of Microbial Biology. 2022;11(44):77-94. https://doi.org/22108/bjm.2022.133007.1459
  • Riedel S, Morse SA, Mietzner T, Miller S. Jawetz Melnick and Adelbergs medical microbiology. USA: MacGraw Hill; 2019.
  • Jebali N, Rabbani Khorasgani M, Kianfar M, Emami H. Evalution of the effects of honey, vinegar and rosewateron adhesion and biofilm formation of Streptococcus mutans and Streptococcus sobrinus. Journal of Isfahan Dental School. 2016;12(3): 232-247. https://sid.ir/paper/126183/en [In Persian]
  • Ducret V, Gonzalez MR, Scrignari T, Perron K. OprD Repression upon metal treatment requires the RNA chaperone Hfq in Pseudomonas aeruginosa. 2016; 7(82):1-15. https://doi.org/10.3390/genes7100082
  • Dori k A, Modarresi F, Shakibaei M R, MA. Frequency of strains producing algD, rhlR, rhlL and aprA genes in clinical isolates of Pseudomonas aeruginosa isolated from patients in hospitals in southern Fars. Pars Journal of Medical Sciences. 2023; 20(2): 47-39. https://doi.org/22034/pjms.2022.700542 [In Persian]
  • Baghbani Arani F, Sharifan M, Mahmoudi Khalidi A. Determination of antibiotic and molecular resistance characteristics of Pseudomonas aeruginosa isolated from cystic fibrosis (CF) patients referred to the Qolhak Pathobiology Laboratory in Tehran during 2016-2018. Journal of Qom University of Medical Sciences. 2019; 13(12): 55-64. https://www.cabidigitallibrary.org/doi/full/10.5555/20203223267
  • Tran NB, Truong QM, Nguyen LQ, Nguyen NM, Tran QH, Dinh TT, Hua VS, Nguyen VD, Lambert PA, Nguyen TT. Prevalence and virulence of commensal Pseudomonas aeruginosa isolates from healthy individuals in Southern Vietnam (2018–2020). 2022; 11(1): 54. https://doi.org/10.3390/biomedicines11010054
  • Al-Zaidi JR. Antibiotic susceptibility patterns of Pseudomonas aeruginosa isolated from clinical and hospital environmental samples in Nasiriyah, Iraq. African Journal of Microbiology Research. 2016;10(23): 844-9. https://doi.org/10.5897/AJMR2016.8042
  • Al-Hasan MN, Wilson JW, Lahr BD, Eckel-Passow JE, Baddour LM. Incidence of Pseudomonas aeruginosa bacteremia: a population-based study. The American Journal of Medicine. 2008; 121(8): 702-8. https://doi.org/1016/j.amjmed.2008.03.029
  • Abdelraheem WM, Ismail DE, Hammad SS. Prevalence of bla OXA-48 and other carbapenemase encoding genes among carbapenem-resistant Pseudomonas aeruginosa clinical isolates in Egypt. BMC Infectious Diseases .2024; 24(1): 1278. https://doi.org/10.1186/s12879-024-10123-7
  • Ahmad Hasan Al-F, Mohammed Jasim Al-S, Haidar Chayad Al-J. The role of oprD gene in the carbapenems resistance in Pseudomonas aeruginosa isolated from burns infection in Al-Najaf province. Al-Kufa University Journal for Biology. 2023; 14(3): 8-16. https://doi.org/10.36320/ajb/v14.i3.11150
  • Mehboudi N, Rahimi HR, Bakhtiari HA, Alimardani M, Jalili A. The impact of probiotic cell-free metabolites in MDR Pseudomonas aeruginosa: antibacterial properties and effect on antibiotic resistance genes expression. Letters in Applied Microbiology. 2023; 76(10): ovad111. https://doi.org/1093/lambio/ovad111
  • Mishra S, Singh S, Raavi. Prevention of OprD regulated antibiotic resistance in Pseudomonas aeruginosa Microbial Pathogenesis. 2017; 112: 221-229. https://doi.org/10.1016/j.micpath.2017.08.007

Gaurav A, Bakht P, Saini M, Pandey S, Pathania R. Role of bacterial efflux pumps in antibiotic resistance, virulence, and strategies to discover novel efflux pump inhibitors. Microbiology. 2023; 169(5): 001333. https://doi.org/10.1099/mic.0.001333 

Journal of Microbial Biology

Articles in Press, Corrected Proof
Available Online from 21 April 2026

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