1887

Abstract

is a multidrug-resistant opportunistic pathogen that affects patients with a compromised immune system and is becoming increasingly important as a hospital-derived infection. This pathogen is difficult to treat owing to its intrinsic multidrug resistance and ability to form antimicrobial-tolerant biofilms. In the present study, we aimed to assess the potential use of zerumbone as a novel anti-biofilm and/or anti-virulence agent against . The results showed that zerumbone at sub-inhibitory doses decreased biofilm formation and disrupted established biofilms. The zerumbone-induced decrease in biofilm formation was dose-dependent based on the results of microtitre plate biofilm assays and confocal laser scanning microscopy. In addition, our data validated the anti-virulence efficacy of zerumbone, wherein it significantly interfered with the motility of . To support these phenotypic results, transcriptional analysis revealed that zerumbone downregulated the expression of biofilm- and virulence-associated genes (, , and ) in . Overall, our findings suggested that zerumbone might be a promising bioactive agent for the treatment of biofilm- and virulence-related infections caused by multidrug-resistant .

Funding
This study was supported by the:
  • National Research Foundation of Korea (Award NRF-2017R1D1A1B03032960)
    • Principle Award Recipient: Yong-Bin Eom
  • Soonchunhyang University (Award SCH-20200312)
    • Principle Award Recipient: Yong-Bin Eom
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.000930
2020-05-28
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/micro/166/8/717.html?itemId=/content/journal/micro/10.1099/mic.0.000930&mimeType=html&fmt=ahah

References

  1. Cisneros JM, Reyes MJ, Pachon J, Becerril B, Caballero FJ et al. Bacteremia due to Acinetobacter baumannii: epidemiology, clinical findings, and prognostic features. Clin Infect Dis 1996; 22:1026–1032 [View Article]
    [Google Scholar]
  2. Gaynes R, Edwards JR. National Nosocomial Infections Surveillance System. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis 2005; 41:848–854
    [Google Scholar]
  3. Yang M, Hu Z, Hu F. Nosocomial meningitis caused by Acinetobacter baumannii: risk factors and their impact on patient outcomes and treatments. Future Microbiol 2012; 7:787–793 [View Article]
    [Google Scholar]
  4. Bergogne-Bérézin E. The increasing role of Acinetobacter species as nosocomial pathogens. Curr Infect Dis Rep 2001; 3:440–444 [View Article]
    [Google Scholar]
  5. Joly-Guillou M-L. Clinical impact and pathogenicity of Acinetobacter . Clin Microbiol Infect 2005; 11:868–873 [View Article]
    [Google Scholar]
  6. Chaari A, Mnif B, Bahloul M, Mahjoubi F, Chtara K et al. Acinetobacter baumannii ventilator-associated pneumonia: epidemiology, clinical characteristics, and prognosis factors. Int J Infect Dis 2013; 17:e1225–e1228 [View Article]
    [Google Scholar]
  7. Perez F, Hujer AM, Hujer KM, Decker BK, Rather PN et al. Global challenge of multidrug-resistant Acinetobacter baumannii . Antimicrob Agents Chemother 2007; 51:3471–3484 [View Article]
    [Google Scholar]
  8. Jain R, Danziger LH. Multidrug-resistant Acinetobacter infections: an emerging challenge to clinicians. Ann Pharmacother 2004; 38:1449–1459 [View Article]
    [Google Scholar]
  9. Tomaras AP, Dorsey CW, Edelmann RE, Actis LA. Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: involvement of a novel chaperone-usher pili assembly system. Microbiology 2003; 149:3473–3484 [View Article]
    [Google Scholar]
  10. Jefferson KK. What drives bacteria to produce a biofilm?. FEMS Microbiol Lett 2004; 236:163–173 [View Article]
    [Google Scholar]
  11. Kennedy P, Brammah S, Wills E, Burns WE. Burns, biofilm and a new appraisal of burn wound sepsis. Burns 2010; 36:49–56 [View Article]
    [Google Scholar]
  12. Singh S, Singh SK, Chowdhury I, Singh R. Understanding the mechanism of bacterial biofilms resistance to antimicrobial agents. Open Microbiol J 2017; 11:53–62 [View Article]
    [Google Scholar]
  13. Singh R, Ray P, Das A, Sharma M. Penetration of antibiotics through Staphylococcus aureus and Staphylococcus epidermidis biofilms. J Antimicrob Chemoth 2010; 65:1955–1958 [View Article]
    [Google Scholar]
  14. Eze E, Chenia H, El Zowalaty M. Acinetobacter baumannii biofilms: effects of physicochemical factors, virulence, antibiotic resistance determinants, gene regulation, and future antimicrobial treatments. Infect Drug Resist 2018; 11:2277–2299 [View Article]
    [Google Scholar]
  15. Hentzer M, Givskov M. Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. J Clin Invest 2003; 112:1300–1307 [View Article]
    [Google Scholar]
  16. Delattin N, De Brucker K, Craik DJ, Cheneval O, Frohlich M et al. Plant-Derived Decapeptide OSIP108 Interferes with Candida albicans Biofilm Formation without Affecting Cell Viability. Antimicrob Agents Chemother 2014; 58:2647–2656 [View Article]
    [Google Scholar]
  17. Lu L, Hu W, Tian Z, Yuan D, Yi G et al. Developing natural products as potential anti-biofilm agents. Chin Med 2019; 14:11 [View Article][PubMed]
    [Google Scholar]
  18. Molhoek EM, van Dijk A, Veldhuizen EJA, Haagsman HP, Bikker FJ. A cathelicidin-2-derived peptide effectively impairs Staphylococcus epidermidis biofilms. Int J Antimicrob Agents 2011; 37:476–479 [View Article]
    [Google Scholar]
  19. de Lima Pimenta A, Chiaradia-Delatorre LD, Mascarello A, de Oliveira KA, Leal PC et al. Synthetic organic compounds with potential for bacterial biofilm inhibition, a path for the identification of compounds interfering with quorum sensing. Int J Antimicrob Agents 2013; 42:519–523 [View Article]
    [Google Scholar]
  20. Imperi F, Fiscarelli EV, Visaggio D, Leoni L, Visca P. Activity and impact on resistance development of two antivirulence fluoropyrimidine drugs in Pseudomonas aeruginosa . Front Cell Infect Microbiol 2019; 9:49 [View Article]
    [Google Scholar]
  21. Yob NJ, Jofrry SM, Affandi MM, Teh LK, Salleh MZ et al. Zingiber zerumbet (L.) Smith: A Review of Its Ethnomedicinal, Chemical, and Pharmacological Uses. Evid Based Complement Alternat Med 2011; 2011:1–12 [View Article]
    [Google Scholar]
  22. Sidahmed HMA, Hashim NM, Abdulla MA, Ali HM, Mohan S et al. Antisecretory, gastroprotective, antioxidant and anti-Helicobcter pylori activity of zerumbone from Zingiber zerumbet (L.) Smith. PLoS One 2015; 10:e0121060 [View Article]
    [Google Scholar]
  23. Shin D-S, Eom Y-B. Zerumbone inhibits Candida albicans biofilm formation and hyphal growth. Can J Microbiol 2019; 65:713–721 [View Article]
    [Google Scholar]
  24. Kim H-R, Rhee K-J, Eom Y-B. Anti-biofilm and antimicrobial effects of zerumbone against Bacteroides fragilis . Anaerobe 2019; 57:99–106 [View Article]
    [Google Scholar]
  25. Xia J, Qian F, Xu W, Zhang Z, Wei X. In vitro inhibitory effects of farnesol and interactions between farnesol and antifungals against biofilms of Candida albicans resistant strains. Biofouling 2017; 33:283–293 [View Article]
    [Google Scholar]
  26. Woo S-G, Lee S-Y, Lee S-M, Lim K-H, Ha E-J et al. Activity of novel inhibitors of Staphylococcus aureus biofilms. Folia Microbiol 2017; 62:157–167 [View Article][PubMed]
    [Google Scholar]
  27. O'Toole GA. Microtiter dish biofilm formation assay. JoVE 2011 [View Article]
    [Google Scholar]
  28. Field D, O’ Connor R, Cotter PD, Ross RP, Hill C. In Vitro Activities of Nisin and Nisin Derivatives Alone and In Combination with Antibiotics against Staphylococcus Biofilms. Front Microbiol 2016; 7:508 [View Article]
    [Google Scholar]
  29. Nosyk O, ter Haseborg E, Metzger U, Frimmel FH. A standardized pre-treatment method of biofilm flocs for fluorescence microscopic characterization. J Microbiol Methods 2008; 75:449–456 [View Article]
    [Google Scholar]
  30. Murray TS, Kazmierczak BI. FlhF is required for swimming and swarming in Pseudomonas aeruginosa . J Bacteriol 2006; 188:6995–7004 [View Article]
    [Google Scholar]
  31. Pereira EM, Schuenck RP, Malvar KL, Iorio NLP, Matos PDM et al. Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus: methicillin-resistant isolates are detected directly in blood cultures by multiplex PCR. Microbiol Res 2010; 165:243–249 [View Article]
    [Google Scholar]
  32. Coyne Sébastien, Guigon G, Courvalin P, Périchon B. Screening and quantification of the expression of antibiotic resistance genes in Acinetobacter baumannii with a microarray. Antimicrob Agents Chemother 2010; 54:333–340 [View Article]
    [Google Scholar]
  33. Azizi O, Shahcheraghi F, Salimizand H, Modarresi F, Shakibaie MR et al. Molecular Analysis and Expression of bap Gene in Biofilm-Forming Multi-Drug-Resistant Acinetobacter baumannii . Rep Biochem Mol Biol 2016; 5:62–72
    [Google Scholar]
  34. Modarresi F, Azizi O, Shakibaie MR, Motamedifar M, Valibeigi B et al. Effect of iron on expression of efflux pump (adeABC) and quorum sensing (luxI, luxR) genes in clinical isolates of Acinetobacter baumannii . APMIS 2015; 123:959–968 [View Article]
    [Google Scholar]
  35. Marchand I, Damier-Piolle L, Courvalin P, Lambert T. Expression of the RND-type efflux pump AdeABC in Acinetobacter baumannii is regulated by the AdeRS two-component system. Antimicrob Agents Chemother 2004; 48:3298–3304 [View Article]
    [Google Scholar]
  36. Fernandes RA, Monteiro DR, Arias LS, Fernandes GL, Delbem ACB et al. Biofilm formation by Candida albicans and Streptococcus mutans in the presence of farnesol: a quantitative evaluation. Biofouling 2016; 32:329–338 [View Article]
    [Google Scholar]
  37. Maragakis LL, Perl TM. Acinetobacter baumannii: epidemiology, antimicrobial resistance, and treatment options. Clin Infect Dis 2008; 46:1254–1263
    [Google Scholar]
  38. Sperandio V. Novel approaches to bacterial infection therapy by interfering with bacteria-to-bacteria signaling. Expert Rev Anti Infect Ther 2007; 5:271–276 [View Article]
    [Google Scholar]
  39. Abdel Wahab SI, Abdul AB, Alzubairi AS, Mohamed Elhassan M, Mohan S. In vitro ultramorphological assessment of apoptosis induced by zerumbone on (HeLa). J Biomed Biotechnol 2009; 2009:1–10 [View Article]
    [Google Scholar]
  40. Tanaka T, Shimizu M, Kohno H, Yoshitani S-ichiro, Tsukio Y et al. Chemoprevention of azoxymethane-induced rat aberrant crypt foci by dietary zerumbone isolated from Zingiber zerumbet . Life Sci 2001; 69:1935–1945 [View Article]
    [Google Scholar]
  41. Keong YS, Alitheen NB, Mustafa S, Abdul Aziz S, Abdul Rahman M et al. Immunomodulatory effects of zerumbone isolated from roots of Zingiber zerumbet . Pak J Pharm Sci 2010; 23:75–82
    [Google Scholar]
  42. Ramirez MS, Penwell WF, Traglia GM, Zimbler DL, Gaddy JA et al. Identification of potential virulence factors in the model strain Acinetobacter baumannii A118. Front Microbiol 2019; 10:1599 [View Article]
    [Google Scholar]
  43. Magnet S, Courvalin P, Lambert T. Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454. Antimicrob Agents Chemother 2001; 45:3375–3380 [View Article]
    [Google Scholar]
  44. Manchanda V, Sinha S, Singh NP. Multidrug resistant Acinetobacter . J Glob Infect Dis 2010; 2:291–304 [View Article]
    [Google Scholar]
  45. Pages JM, Amaral L. Mechanisms of drug efflux and strategies to combat them: challenging the efflux pump of Gram-negative bacteria. Biochim Biophys Acta 1794; 2009:826–833
    [Google Scholar]
  46. Yoon E-J, Nait Chabane Y, Goussard S, Snesrud E, Courvalin P et al. Contribution of resistance-nodulation-cell division efflux systems to antibiotic resistance and biofilm formation in Acinetobacter baumannii . mBio 2015; 6: [View Article]
    [Google Scholar]
  47. Richmond GE, Evans LP, Anderson MJ, Wand ME, Bonney LC et al. The Acinetobacter baumannii Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner. mBio 2016; 7:e00430–00416 [View Article]
    [Google Scholar]
  48. Loehfelm TW, Luke NR, Campagnari AA. Identification and characterization of an Acinetobacter baumannii biofilm-associated protein. J Bacteriol 2008; 190:1036–1044 [View Article]
    [Google Scholar]
  49. Roilides E, Simitsopoulou M, Katragkou A, Walsh TJ. How biofilms evade host defenses. Microbiol Spectr 2015; 3: [View Article]
    [Google Scholar]
  50. Duan L, Perez RE, Davaadelger B, Dedkova EN, Blatter LA et al. P53-Regulated autophagy is controlled by glycolysis and determines cell fate. Oncotarget 2015; 6:23135–23156 [View Article]
    [Google Scholar]
  51. Haghighi F, Mohammadi SR, Mohammadi P, Eskandari M, Hosseinkhani S. The evaluation of Candida albicans biofilms formation on silicone catheter, PVC and glass coated with titanium dioxide nanoparticles by XTT method and ATPase assay. BLL 2012; 113:707–711 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.000930
Loading
/content/journal/micro/10.1099/mic.0.000930
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error