Modulating the transcriptomic profile of multidrug-resistant Klebsiella pneumoniae biofilm formation by antibiotics in combination with zinc sulfate.
Antibiotics
Biofilm
Combination
Klebsiella pneumoniae
Multidrug-resistant
Zinc sulfate
Journal
Annals of clinical microbiology and antimicrobials
ISSN: 1476-0711
Titre abrégé: Ann Clin Microbiol Antimicrob
Pays: England
ID NLM: 101152152
Informations de publication
Date de publication:
12 Sep 2023
12 Sep 2023
Historique:
received:
29
06
2023
accepted:
29
08
2023
medline:
14
9
2023
pubmed:
13
9
2023
entrez:
12
9
2023
Statut:
epublish
Résumé
Klebsiella pneumoniae is a significant healthcare-associated pathogen. We investigated the antimicrobial interaction pattern between zinc sulfate and antibiotics against K. pneumoniae biofilm on the phenotypic and genotypic levels. Determining the minimum biofilm inhibitory concentrations and the transcriptomic profile of K. pneumoniae biofilm formation genes post-treatment were carried out to evaluate the effect on the phenotypic and genotypic levels, respectively. Zinc enhanced the antibiofilm potentials of cephalosporins, aminoglycosides, and ertapenem, whereas it antagonizes the effectiveness of fluoroquinolones and meropenem on the phenotypic level. On the molecular level, zinc enhanced the anti-biofilm efficacies of cephalosporins (cefotaxime, ceftriaxone, ceftazidime, cefpirome, and cefepime) via down-regulating the expression of biofilm-related genes by 18-, 38-, 5-, 77- and 2-folds, respectively. Zinc in combination with aminoglycosides (kanamycin, gentamicin, and amikacin) reduced the expression of biofilm-related genes by 40-, 2602- and 20-folds, respectively, and by 2-folds in combination with ertapenem. However, a reduction in the down-regulatory potentials of fluoroquinolones was recorded following combination with zinc by 2-, 2-, 15- and 14-folds, respectively, and an up-regulation in the expression levels of the tested genes by 2-folds in the case of zinc/meropenem combination. Results revealed variable interaction patterns between different antibiotics in combination with zinc. Current findings also shed light on the antibiofilm potentials of zinc/antibiotics combinations especially when combining zinc with fluoroquinolones or meropenem to avoid their antagonistic effects.
Sections du résumé
BACKGROUND
BACKGROUND
Klebsiella pneumoniae is a significant healthcare-associated pathogen. We investigated the antimicrobial interaction pattern between zinc sulfate and antibiotics against K. pneumoniae biofilm on the phenotypic and genotypic levels.
METHODS
METHODS
Determining the minimum biofilm inhibitory concentrations and the transcriptomic profile of K. pneumoniae biofilm formation genes post-treatment were carried out to evaluate the effect on the phenotypic and genotypic levels, respectively.
RESULTS
RESULTS
Zinc enhanced the antibiofilm potentials of cephalosporins, aminoglycosides, and ertapenem, whereas it antagonizes the effectiveness of fluoroquinolones and meropenem on the phenotypic level. On the molecular level, zinc enhanced the anti-biofilm efficacies of cephalosporins (cefotaxime, ceftriaxone, ceftazidime, cefpirome, and cefepime) via down-regulating the expression of biofilm-related genes by 18-, 38-, 5-, 77- and 2-folds, respectively. Zinc in combination with aminoglycosides (kanamycin, gentamicin, and amikacin) reduced the expression of biofilm-related genes by 40-, 2602- and 20-folds, respectively, and by 2-folds in combination with ertapenem. However, a reduction in the down-regulatory potentials of fluoroquinolones was recorded following combination with zinc by 2-, 2-, 15- and 14-folds, respectively, and an up-regulation in the expression levels of the tested genes by 2-folds in the case of zinc/meropenem combination.
CONCLUSIONS
CONCLUSIONS
Results revealed variable interaction patterns between different antibiotics in combination with zinc. Current findings also shed light on the antibiofilm potentials of zinc/antibiotics combinations especially when combining zinc with fluoroquinolones or meropenem to avoid their antagonistic effects.
Identifiants
pubmed: 37700331
doi: 10.1186/s12941-023-00634-7
pii: 10.1186/s12941-023-00634-7
pmc: PMC10498587
doi:
Substances chimiques
Anti-Bacterial Agents
0
Zinc Sulfate
7733-02-0
Meropenem
FV9J3JU8B1
Ertapenem
G32F6EID2H
Zinc
J41CSQ7QDS
Cephalosporins
0
Fluoroquinolones
0
Aminoglycosides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
84Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
Références
Nirwati H, Sinanjung K, Fahrunissa F, Wijaya F, Napitupulu S, Hati VP, Hakim MS, Meliala A, Aman AT, Nuryastuti T. Biofilm formation and antibiotic resistance of Klebsiella pneumoniae isolated from clinical samples in a tertiary care hospital, Klaten, Indonesia. InBMC proceedings. BioMed Central. 2019;13(11):1–8.
Murphy CN, Clegg S. Klebsiella pneumoniae and type 3 fimbriae: nosocomial infection, regulation and biofilm formation. Future Microbiol. 2012;7(8):991–1002.
doi: 10.2217/fmb.12.74
pubmed: 22913357
Guerra MES, Destro G, Vieira B, Lima AS, Ferraz LFC, Hakansson AP, Darrieux M, Converso TR. Klebsiella pneumoniae biofilms and their role in disease pathogenesis. Front Cell Infect Microbiol. 2022. https://doi.org/10.3389/fcimb.2022.877995 .
doi: 10.3389/fcimb.2022.877995
pubmed: 35646720
pmcid: 9132050
Wasfi R, Elkhatib WF, Ashour HM. Molecular typing and virulence analysis of multidrug resistant Klebsiella pneumoniae clinical isolates recovered from Egyptian hospitals. Sci Rep. 2016;6(1):38929.
doi: 10.1038/srep38929
pubmed: 28004732
pmcid: 5177892
Elkhatib WF, Khairalla AS, Ashour HM. Evaluation of different microtiter plate-based methods for the quantitative assessment of Staphylococcus aureus biofilms. Future Microbiol. 2014;9(6):725–35.
doi: 10.2217/fmb.14.33
pubmed: 25046520
Elkhatib W, Noreddin A. In vitro antibiofilm efficacies of different antibiotic combinations with zinc sulfate against Pseudomonas aeruginosa recovered from hospitalized patients with urinary tract infection. Antibiotics. 2014;3(1):64–84.
doi: 10.3390/antibiotics3010064
pubmed: 27025734
pmcid: 4790350
Vuotto C, Longo F, Pascolini C, Donelli G, Balice M, Libori M, Tiracchia V, Salvia A, Varaldo P. Biofilm formation and antibiotic resistance in Klebsiella pneumoniae urinary strains. J Appl Microbiol. 2017;123(4):1003–18.
doi: 10.1111/jam.13533
pubmed: 28731269
Wu C, Labrie J, Tremblay Y, Haine D, Mourez M, Jacques M. Zinc as an agent for the prevention of biofilm formation by pathogenic bacteria. J Appl Microbiol. 2013;115(1):30–40.
doi: 10.1111/jam.12197
pubmed: 23509865
Khalil MA, Hager R, Abd-El Reheem F, Mahmoud EE, Samir T, Moawad SS, Hefzy EM. A study of the virulence traits of carbapenem-resistant Klebsiella pneumoniae isolates in a Galleria mellonella model. Microb Drug Resist. 2019;25(7):1063–71.
doi: 10.1089/mdr.2018.0270
pubmed: 31033413
Wayne P. Clinical and laboratory standards institute. Performance standards for antimicrobial susceptibility testing. 2011.
Farkas A, Pap B, Kondorosi É, Maróti G. Antimicrobial activity of NCR plant peptides strongly depends on the test assays. Front Microbiol. 2018;9:2600.
doi: 10.3389/fmicb.2018.02600
pubmed: 30425705
pmcid: 6218624
Černohorská L, Votava M. Antibiotic synergy against biofilm-forming Pseudomonas aeruginosa. Folia Microbiol. 2008;53(1):57–60.
doi: 10.1007/s12223-008-0008-z
Shenkutie AM, Yao MZ, Siu GK-H, Wong BKC, Leung PH-M. Biofilm-induced antibiotic resistance in clinical Acinetobacter baumannii isolates. Antibiotics. 2020;9(11):817.
doi: 10.3390/antibiotics9110817
pubmed: 33212840
pmcid: 7698371
Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3(6):1101–8.
doi: 10.1038/nprot.2008.73
pubmed: 18546601
Wu C-C, Lin C-T, Cheng W-Y, Huang C-J, Wang Z-C, Peng H-L. Fur-dependent MrkHI regulation of type 3 fimbriae in Klebsiella pneumoniae CG43. Microbiology. 2012;158(4):1045–56.
doi: 10.1099/mic.0.053801-0
pubmed: 22262101
Abdelaziz NA, Elkhatib WF, Sherif MM, Abourehab MA, Al-Rashood ST, Eldehna WM, Mostafa NM, Elleboudy NS. In silico docking, resistance modulation and biofilm gene expression in multidrug-resistant Acinetobacter baumannii via cinnamic and gallic acids. Antibiotics. 2022;11(7):870.
doi: 10.3390/antibiotics11070870
pubmed: 35884124
pmcid: 9311515
Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Wayne: Clinical and Laboratory Standards Institute; 2017.
Kewcharoenwong C, Sein MM, Nithichanon A, Khongmee A, Wessells KR, Hinnouho G-M, Barffour MA, Kounnavong S, Hess SY, Stephensen CB. Daily preventive zinc supplementation increases the antibody response against pathogenic Escherichia coli in children with zinc insufficiency: a randomised controlled trial. Sci Rep. 2022;12(1):1–9.
doi: 10.1038/s41598-022-20445-8
Mulcahy LR, Burns JL, Lory S, Lewis K. Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis. J Bacteriol. 2010;192(23):6191–9.
doi: 10.1128/JB.01651-09
pubmed: 20935098
pmcid: 2981199
Moriarty T, Elborn J, Tunney M. Effect of pH on the antimicrobial susceptibility of planktonic and biofilm-grown clinical Pseudomonas aeruginosa isolates. Br J Biomed Sci. 2007;64(3):101–4.
doi: 10.1080/09674845.2007.11732766
pubmed: 17910277
Ashwath P, Deekshit VK, Rohit A, Dhinakaran I, Karunasagar I, Karunasagar I, Akhila DS. Biofilm formation and associated gene expression in multidrug-resistant Klebsiella pneumoniae isolated from clinical specimens. Curr Microbiol. 2022;79(3):1–10.
doi: 10.1007/s00284-022-02766-z
Mulcahy H, Charron-Mazenod L, Lewenza S. Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms. PLoS Pathog. 2008;4(11):e1000213.
doi: 10.1371/journal.ppat.1000213
pubmed: 19023416
pmcid: 2581603
Hancock V, Dahl M, Klemm P. Abolition of biofilm formation in urinary tract Escherichia coli and Klebsiella isolates by metal interference through competition for fur. Appl Environ Microbiol. 2010;76(12):3836–41.
doi: 10.1128/AEM.00241-10
pubmed: 20418434
pmcid: 2893501
Jenal U, Malone J. Mechanisms of cyclic-di-GMP signaling in bacteria. Annu Rev Genet. 2006;40:385–407.
doi: 10.1146/annurev.genet.40.110405.090423
pubmed: 16895465
Isaei E, Mansouri S, Mohammadi F, Taheritarigh S, Mohammadi Z. Novel combinations of synthesized ZnO NPs and ceftazidime: evaluation of their activity against standards and new clinically isolated Pseudomonas aeruginosa. Avicenna J Med Biotechnol. 2016;8(4):169.
pubmed: 27920884
pmcid: 5124253
Vos M, Sibleyras L, Lo LK, Hesse E, Gaze W, Klümper U. Zinc can counteract selection for ciprofloxacin resistance. FEMS Microbiol Lett. 2020;367(3):fnaa038.
doi: 10.1093/femsle/fnaa038
pubmed: 32105320
pmcid: 7082703
Turel I. The interactions of metal ions with quinolone antibacterial agents. Coord Chem Rev. 2002;232(1–2):27–47.
doi: 10.1016/S0010-8545(02)00027-9
Lemire JA, Harrison JJ, Turner RJ. Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat Rev Microbiol. 2013;11(6):371–84.
doi: 10.1038/nrmicro3028
pubmed: 23669886
Klümper U, Maillard A, Hesse E, Bayer F, van Houte S, Longdon B, Gaze W, Buckling A. Short-term evolution under copper stress increases probability of plasmid uptake. BioRxiv. 2019. https://doi.org/10.1101/610873 .
doi: 10.1101/610873
Principe L, Vecchio G, Sheehan G, Kavanagh K, Morroni G, Viaggi V, di Masi A, Giacobbe DR, Luzzaro F, Luzzati R. Zinc chelators as Carbapenem adjuvants for Metallo-β-lactamase-producing bacteria: in vitro and in vivo evaluation. Microb Drug Resist. 2020;26(10):1133–43.
doi: 10.1089/mdr.2020.0037
pubmed: 32364820
Murphy TA, Catto LE, Halford SE, Hadfield AT, Minor W, Walsh TR, Spencer J. Crystal structure of Pseudomonas aeruginosa SPM-1 provides insights into variable zinc affinity of metallo-β-lactamases. J Mol Biol. 2006;357(3):890–903.
doi: 10.1016/j.jmb.2006.01.003
pubmed: 16460758
Liu Y-L, Zhang M-N, Tong G-Y, Sun S-Y, Zhu Y-H, Cao Y, Zhang J, Huang H, Niu B, Li H. The effectiveness of zinc supplementation in men with isolated hypogonadotropic hypogonadism. Asian J Androl. 2017;19(3):280.
doi: 10.4103/1008-682X.189621
pubmed: 27768007