Volume 11, Issue 2 (6-2023)                   JoMMID 2023, 11(2): 86-95 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Najafi M M. Meropenem inhibits Acinetobacter baumannii biofilm formation by downregulating pgaA gene expression. JoMMID 2023; 11 (2) :86-95
URL: http://jommid.pasteur.ac.ir/article-1-400-en.html
Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
Abstract:   (817 Views)
Introduction: Acinetobacter baumannii is the cause of nosocomial infections, primarily in intensive care units. The pgaA gene plays an essential role in biofilm formation, making it a promising target for developing new strategies to tackle A. baumannii infections. This study investigated the meropenem effect on pgaA gene expression and biofilm formation in A. baumannii. Methods: Over five months, 50 urine samples were taken from patients receiving medical care in the intensive care unit, of which 20 A. baumannii isolates were detected. Antibiotic susceptibility was determined with meropenem, imipenem, trimethoprim/sulfamethoxazole, ceftazidime, ciprofloxacin, tetracycline, amikacin, as well as gentamicin disks by the Kirby-Bauer method. The minimum inhibitory concentration (MIC) of meropenem was determined using the microdilution method. Biofilm formation was investigated through the tissue culture plate (TCP) technique and imaged using an atomic force microscope (AFM). Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) determined the expression level of the pgaA gene. Results: Antibiotic susceptibility testing revealed that all A. baumannii isolates were resistant to meropenem, imipenem, ciprofloxacin, and amikacin, and 71.42% were resistant to tetracycline. The MIC for meropenem could not be determined for isolates. Meropenem prevented biofilm formation in more than 70% of the isolates, and AFM imaging revealed thin biofilms. The RT-PCR showed that exposure to meropenem significantly decreased the pgaA expression gene in over 95% of the isolates (P < 0.0001). Conclusion: Meropenem inhibited biofilm formation in most A. baumannii isolates by downregulating the pgaA expression, suggesting a potential role in preventing A. baumannii infections by reducing biofilm formation
Full-Text [PDF 1196 kb]   (304 Downloads)    
Type of Study: Original article | Subject: Anti-microbial agents, resistance and treatment protocols
Received: 2021/09/28 | Accepted: 2023/06/11 | Published: 2023/07/18

1. Brooks GF, Carroll KC, Butel JS, Morse SA. Jawetz, Melnick & Adelberg's Medical Microbiology. 24th ed. USA: McGraw-Hill; 2007. 273-5.
2. Huang LY, Chen TL, Lu PL, Tsai CA, Cho WL, Chang FY, et al. Dissemination of multidrug-resistant, class 1 integron-carrying Acinetobacter baumannii isolates in Taiwan. Clin Microbiol Infect. 2008; 14 (11): 1010-9. [DOI:10.1111/j.1469-0691.2008.02077.x] [PMID]
3. Cisneros JM, Rodríguez-Baño J. Nosocomial bacteremia due to Acinetobacter baumannii: epidemiology, clinical features and treatment. Clin Microbiol Infect. 2002; 8 (11): 687-93. [DOI:10.1046/j.1469-0691.2002.00487.x] [PMID]
4. O'Shea MK. Acinetobacter in modern warfare. Int J Antimicrob Agents. 2012; 39 (5): 363-75. [DOI:10.1016/j.ijantimicag.2012.01.018] [PMID]
5. Abdi SN, Ghotaslou R, Ganbarov K, Mobed A, Tanomand A, Yousefi M, et al. Acinetobacter baumannii Efflux Pumps and Antibiotic Resistance. Infect Drug Resist. 2020; 13: 423-34. [DOI:10.2147/IDR.S228089] [PMID] [PMCID]
6. Nasiri MJ, Zamani S, Fardsanei F, Arshadi M, Bigverdi R, Hajikhani B, et al. Prevalence and Mechanisms of Carbapenem Resistance in Acinetobacter baumannii: A Comprehensive Systematic Review of Cross-Sectional Studies from Iran. Microb Drug Resist. 2020; 26 (3): 270-83. [DOI:10.1089/mdr.2018.0435] [PMID]
7. Talbot GH, Bradley J, Edwards JE, Jr., Gilbert D, Scheld M, Bartlett JG. Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis. 2006; 42 (5): 657-68. [DOI:10.1086/499819] [PMID]
8. Fournier PE, Richet H, Weinstein RA. The Epidemiology and Control of Acinetobacter baumannii in Health Care Facilities. Clin Infect Dis. 2006; 42 (5): 692-9. [DOI:10.1086/500202] [PMID]
9. Zarrilli R. Acinetobacter baumannii virulence determinants involved in biofilm growth and adherence to host epithelial cells. Virulence. 2016; 7 (4): 367-8. [DOI:10.1080/21505594.2016.1150405] [PMID] [PMCID]
10. Wroblewska MM, Sawicka-Grzelak A, Marchel H, Luczak M, Sivan A. Biofilm production by clinical strains of Acinetobacter baumannii isolated frompatients hospitalized in two tertiary care hospitals. FEMS Immunol Med Microbiol. 2008; 53 (1): 140-4. [DOI:10.1111/j.1574-695X.2008.00403.x] [PMID]
11. Falciglia G, Hageman JR, Schreiber M, Alexander K. Antibiotic Therapy and Early Onset Sepsis. NeoReviews. 2012; 13 (2): e86. [DOI:10.1542/neo.13-2-e86]
12. Lopes BS, Amyes SGB. Role of ISAba1 and ISAba125 in governing the expression of blaADC in clinically relevant Acinetobacter baumannii strains resistant to cephalosporins. J Med Microbiol. 2012; 61 (8): 1103-8. [DOI:10.1099/jmm.0.044156-0] [PMID]
13. Gu B, Tong M, Zhao W, Liu G, Ning M, Pan S, et al. Prevalence and Characterization of Class I Integrons among Pseudomonas aeruginosa and Acinetobacter baumannii Isolates from Patients in Nanjing, China. J Clin Microbiol. 2007; 45 (1): 241-3. [DOI:10.1128/JCM.01318-06] [PMID] [PMCID]
14. Bou G, Cerveró G, Domínguez MA, Quereda C, Martínez-Beltrán J. Characterization of a Nosocomial Outbreak Caused by a Multiresistant Acinetobacter baumannii Strain with a Carbapenem-Hydrolyzing Enzyme: High-Level Carbapenem Resistance in A. baumannii Is Not Due Solely to the Presence of β-Lactamases. J Clin Microbiol. 2000; 38 (9): 3299-305. [DOI:10.1128/JCM.38.9.3299-3305.2000] [PMID] [PMCID]
15. Sutherland IW. The biofilm matrix - an immobilized but dynamic microbial environment. Trends Microbiol. 2001;9 (5): 222-7. [DOI:10.1016/S0966-842X(01)02012-1] [PMID]
16. Stoodley P, Sauer K, Davies DG, Costerton JW. Biofilms as Complex Differentiated Communities. Annu Rev Microbiol. 2002; 56 (1): 187-209. [DOI:10.1146/annurev.micro.56.012302.160705] [PMID]
17. De la Fuente-Núñez C, Korolik V, Bains M, Nguyen U, Breidenstein EBM, Horsman S, et al. Inhibition of Bacterial Biofilm Formation and Swarming Motility by a Small Synthetic Cationic Peptide. Antimicrob Agents Chemother. 2012; 56 (5): 2696-704. [DOI:10.1128/AAC.00064-12] [PMID] [PMCID]
18. Gaddy JA, Actis LA. Regulation of Acinetobacter baumannii biofilm formation. Future Microbiol. 2009; 4 (3): 273-8. [DOI:10.2217/fmb.09.5] [PMID] [PMCID]
19. Bassler BL. How bacteria talk to each other: regulation of gene expression by quorum sensing. Curr Opin Microbiol. 1999; 2 (6): 582-7. [DOI:10.1016/S1369-5274(99)00025-9] [PMID]
20. Goh HMS, Beatson SA, Totsika M, Moriel DG, Phan M-D, Szubert J, et al. Molecular Analysis of the Acinetobacter baumannii Biofilm-Associated Protein. Appl Environ Microbiol. 2013; 79 (21): 6535-43. [DOI:10.1128/AEM.01402-13] [PMID] [PMCID]
21. Choi AHK, Slamti L, Avci FY, Pier GB, Maira-Litrán T. The pgaABCD Locus of Acinetobacter baumannii Encodes the Production of Poly-β-1-6-N-Acetylglucosamine, Which Is Critical for Biofilm Formation. J Clin Microbiol. 2009; 191 (19): 5953-63. [DOI:10.1128/JB.00647-09] [PMID] [PMCID]
22. Longo F, Vuotto C, Donelli G. Biofilm formation in Acinetobacter baumannii. New Microbiol. 2014; 37 (2): 119-27.
23. Dubrovin EV, Popova AV, Kraevskiy SV, Ignatov SG, Ignatyuk TE, Yaminsky IV, et al. Atomic Force Microscopy Analysis of the Acinetobacter baumannii Bacteriophage AP22 Lytic Cycle. PLoS ONE. 2012; 7 (10): e47348. [DOI:10.1371/journal.pone.0047348] [PMID] [PMCID]
24. Soon RL, Nation RL, Harper M, Adler B, Boyce JD, Tan C-H, et al. Effect of colistin exposure and growth phase on the surface properties of live Acinetobacter baumannii cells examined by atomic force microscopy. Int J Antimicrob Agents. 2011; 38 (6): 493-501. [DOI:10.1016/j.ijantimicag.2011.07.014] [PMID] [PMCID]
25. Ghajavand H, Esfahani BN, Havaei SA, Moghim S, Fazeli H. Molecular identification of Acinetobacter baumannii isolated from intensive care units and their antimicrobial resistance patterns. Adv Biomed Res. 2015; 4: 110. [DOI:10.4103/2277-9175.157826] [PMID] [PMCID]
26. Hudzicki J. Kirby-Bauer disk diffusion susceptibility test protocol: American Society for Microbiology; 2009 [updated 08 December. 1-23]. Available from: https://www.asmscience.org/content/education/protocol/protocol.3189?crawler=true.
27. Weinstein MP, Patel JB, Campeau S, Eliopoulos GM, Marcelo MF, Humphries RM, et al. Performance Standards for Antimicrobial Susceptibility Testing M100. 28th ed. USA: Clinical and Laboratory Standards Institute (CLSI); 2018.
28. Jorgensen JH, Ferraro MJ. Antimicrobial susceptibility testing: a review of general principles and contemporary practices. Clin Infect Dis. 2009; 49 (11): 1749-55. [DOI:10.1086/647952] [PMID]
29. Mathur T, Singhal S, Khan S, Upadhyay DJ, Fatma T, Rattan A. Detection of biofilm formation among the clinical isolates of Staphylococci: an evaluation of three different screening methods. Indian J Med Microbiol. 2006;24(1):25-9. https://doi.org/10.1016/S0255-0857(21)02466-X [DOI:10.4103/0255-0857.19890] [PMID]
30. Nosrati N, Honarmand Jahromy S, Zare Karizi S. Comparison of Tissue Culture Plate, Congo red Agar and Tube Methods for Evaluation of Biofilm Formation among Uropathogenic E. coli Isolates. Iran J Med Microbiol. 2017; 11 (3): 49-58.
31. StepanoviĆ S, VukoviĆ D, Hola V, Bonaventura GD, DjukiĆ S, ĆIrkoviĆ I, et al. Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. APMIS. 2007; 115 (8): 891-9. [DOI:10.1111/j.1600-0463.2007.apm_630.x] [PMID]
32. Tollersrud T, Berge T, Andersen SR, Lund A. Imaging the surface of Staphylococcus aureus by atomic force microscopy. APMIS. 2001; 109 (7‐8): 541-5. [DOI:10.1111/j.1600-0463.2001.907808.x] [PMID]
33. Boudjemaa R, Steenkeste K, Canette A, Briandet R, Fontaine-Aupart M-P, Marlière C. Direct observation of the cell-wall remodeling in adhering Staphylococcus aureus 27217: An AFM study supported by SEM and TEM. Cell Surf. 2019; 5: 100018. [DOI:10.1016/j.tcsw.2019.100018] [PMID] [PMCID]
34. Chao Y, Zhang T. Optimization of fixation methods for observation of bacterial cell morphology and surface ultrastructures by atomic force microscopy. Appl Microbiol Biotechnol. 2011; 92 (2): 381-92. [DOI:10.1007/s00253-011-3551-5] [PMID] [PMCID]
35. Liu BY, Zhang GM, Li XL, Chen H. Effect of glutaraldehyde fixation on bacterial cells observed by atomic force microscopy. Scanning. 2012; 34 (1): 6-11. [DOI:10.1002/sca.20269] [PMID]
36. Eales MG, Ferrari E, Goddard AD, Lancaster L, Sanderson P, Miller C. Mechanistic and phenotypic studies of bicarinalin, BP100 and colistin action on Acinetobacter baumannii. Res Microbiol. 2018; 169 (6): 296-302. [DOI:10.1016/j.resmic.2018.04.005] [PMID]
37. Marinho AR, Martins PD, Ditmer EM, d'Azevedo PA, Frazzon J, Sand STVD, et al. Biofilm formation on polystyrene under different temperatures by antibiotic resistant Enterococcus faecalis and Enterococcus faecium isolated from food. Braz J Microbiol. 2013; 44 (2): 423-6. [DOI:10.1590/S1517-83822013005000045] [PMID] [PMCID]
38. Selasi GN, Nicholas A, Jeon H, Na SH, Kwon HI, Kim YJ, et al. Differences in Biofilm Mass, Expression of Biofilm-Associated Genes, and Resistance to Desiccation between Epidemic and Sporadic Clones of Carbapenem-Resistant Acinetobacter baumannii Sequence Type 191. PLoS ONE. 2016; 11 (9): e0162576. [DOI:10.1371/journal.pone.0162576] [PMID] [PMCID]
39. Clifford RJ, Milillo M, Prestwood J, Quintero R, Zurawski DV, Kwak YI, et al. Detection of Bacterial 16S rRNA and Identification of Four Clinically Important Bacteria by Real-Time PCR. PLoS ONE. 2012; 7 (11): e48558. [DOI:10.1371/journal.pone.0048558] [PMID] [PMCID]
40. Nasr P. Genetics, epidemiology, and clinical manifestations of multidrug-resistant Acinetobacter baumannii. J Hosp Infect. 2020; 104 (1): 4-11. [DOI:10.1016/j.jhin.2019.09.021] [PMID]
41. Howard A, O'Donoghue M, Feeney A, Sleator RD. Acinetobacter baumannii. Virulence. 2012; 3 (3): 243-50. [DOI:10.4161/viru.19700] [PMID] [PMCID]
42. Klevens RM, Edwards JR, Richards CL, Horan TC, Gaynes RP, Pollock DA, et al. Estimating Health Care-Associated Infections and Deaths in U.S. Hospitals, 2002. Publ Health Rep. 2007; 122 (2): 160-6. [DOI:10.1177/003335490712200205] [PMID] [PMCID]
43. Jahangiri S, Malekzadegan Y, Motamedifar M, Hadi N. Virulence genes profile and biofilm formation ability of Acinetobacter baumannii strains isolated from inpatients of a tertiary care hospital in southwest of Iran. Gene Rep. 2019; 17: 100481. [DOI:10.1016/j.genrep.2019.100481]
44. Motbainor H, Bereded F, Mulu W. Multi-drug resistance of blood stream, urinary tract and surgical site nosocomial infections of Acinetobacter baumannii and Pseudomonas aeruginosa among patients hospitalized at Felegehiwot referral hospital, Northwest Ethiopia: a cross-sectional study. BMC Infect Dis. 2020; 20 (1): 92. [DOI:10.1186/s12879-020-4811-8] [PMID] [PMCID]
45. Afshar Yavari SH, Rota S, Caglar K, Fidan I. DETERMINATION OF RESISTANCE PATTERN OF ISOLATED ACINETOBACTER BAUMANNII FROM INTENSIVE CARE UNITS (ICUS) IN GAZI HOSPITAL, ANKARA. Nursing and Midwifery Journal 2016; 13 (10) : 912-918. URL: http://unmf.umsu.ac.ir/article-1-2772-en.html
46. Farsiani H, Mosavat A, Soleimanpour S, Nasab MN, Salimizand H, Jamehdar SA, et al. Limited genetic diversity and extensive antimicrobial resistance in clinical isolates of Acinetobacter baumannii in north-east Iran. J Med Microbiol. 2015; 64 (7): 767-73. [DOI:10.1099/jmm.0.000090] [PMID]
47. Moradi J, Hashemi FB, Bahador A. Antibiotic Resistance of Acinetobacter baumannii in Iran: A Systemic Review of the Published Literature. Osong Public Health Res Perspect. 2015; 6 (2): 79-86. [DOI:10.1016/j.phrp.2014.12.006] [PMID] [PMCID]
48. Beganovic M, Luther MK, Daffinee KE, LaPlante KL. Biofilm prevention concentrations (BPC) of minocycline compared to polymyxin B, meropenem, and amikacin against Acinetobacter baumannii. Diagn Microbiol Infect Dis. 2019; 94 (3): 223-6. [DOI:10.1016/j.diagmicrobio.2019.01.016] [PMID]
49. Wang Y-C, Kuo S-C, Yang Y-S, Lee Y-T, Chiu C-H, Chuang M-F, et al. Individual or Combined Effects of Meropenem, Imipenem, Sulbactam, Colistin, and Tigecycline on Biofilm-Embedded Acinetobacter baumannii and Biofilm Architecture. Antimicrob Agents Chemother. 2016; 60 (8): 4670-6. [DOI:10.1128/AAC.00551-16] [PMID] [PMCID]
50. Yang C-H, Su P-W, Moi S-H, Chuang L-Y. Biofilm Formation in Acinetobacter Baumannii: Genotype-Phenotype Correlation. Molecules. 2019; 24 (10): 1849. [DOI:10.3390/molecules24101849] [PMID] [PMCID]
51. Perez LRR. Acinetobacter baumannii displays inverse relationship between meropenem resistance and biofilm production. J Chemother. 2015; 27 (1): 13-6. [DOI:10.1179/1973947813Y.0000000159] [PMID]
52. Bazari PAM, Honarmand Jahromy S, Zare Karizi S. Phenotypic and genotypic characterization of biofilm formation among Staphylococcus aureus isolates from clinical specimens, an Atomic Force Microscopic (AFM) study. Microb Pathog. 2017; 110: 533-9. [DOI:10.1016/j.micpath.2017.07.041] [PMID]
53. Honarmand jahromi S, Noorbakhsh F, Hosseini O, Sajdeh A. Visualization of acidic and alkaline pH effect on biofilm formation of Staphylococcus aureus isolates by Atomic force microscope. Int J Mol Clin Microbiol. 2018; 8 (1): 942-9.
54. Hatami R. The frequency of multidrug-resistance and extensively drug-resistant Acinetobacter baumannii in west of Iran. J Exp Clin Med. 2018; 1 (1): 4-8.

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.