Antibiofilm and Antivirulence Efficacies of Flavonoids and Curcumin Against Acinetobacter baumannii

Acinetobacter baumannii is well adapted to hospital environments, and the persistence of its chronic infections is mainly due to its ability to form biofilms resistant to conventional antibiotics and host immune systems. Hence, the inhibitions of biofilm formation and virulence characteristics provide other means of addressing infections. In this study, the antibiofilm activities of twelve flavonoids were initially investigated. Three most active flavonoids, namely, fisetin, phloretin, and curcumin, dose-dependently inhibited biofilm formation by a reference A. baumannii strain and by several clinical isolates, including four multidrug-resistant isolates. Furthermore, the antibiofilm activity of curcumin (the most active flavonoid) was greater than that of the well-known biofilm inhibitor gallium nitrate. Curcumin inhibited pellicle formation and the surface motility of A. baumannii. Interestingly, curcumin also showed antibiofilm activity against Candida albicans and mixed cultures of C. albicans and A. baumannii. In silico molecular docking of the biofilm response regulator BfmR showed that the binding efficacy of flavonoids with BfmR was correlated with antibiofilm efficacy. In addition, curcumin treatment diminished A. baumannii virulence in an in vivo Caenorhabditis elegans model without cytotoxicity. The study shows curcumin and other flavonoids have potential for controlling biofilm formation by and the virulence of A. baumannii.

[1]  D. Moser,et al.  Antibiofilm efficacy of curcumin in combination with 2-aminobenzimidazole against single- and mixed-species biofilms of Candida albicans and Staphylococcus aureus. , 2019, Colloids and surfaces. B, Biointerfaces.

[2]  S. K. Rajasekharan,et al.  LED based real-time survival bioassays for nematode research , 2018, Scientific Reports.

[3]  Prince Sharma,et al.  Curcumin alleviates persistence of Acinetobacter baumannii against colistin , 2018, Scientific Reports.

[4]  S. Knight,et al.  Structural basis forAcinetobacter baumanniibiofilm formation. , 2018 .

[5]  S. Knight,et al.  Structural basis for Acinetobacter baumannii biofilm formation , 2018, Proceedings of the National Academy of Sciences.

[6]  S. Filler,et al.  The Hyr1 protein from the fungus Candida albicans is a cross kingdom immunotherapeutic target for Acinetobacter bacterial infection , 2018, PLoS pathogens.

[7]  J. Cavanagh,et al.  The Structure of the Biofilm-controlling Response Regulator BfmR from Acinetobacter baumannii Reveals Details of Its DNA-binding Mechanism. , 2018, Journal of molecular biology.

[8]  P. Mishra,et al.  Antimicrobial and antibiofilm activity of curcumin-silver nanoparticles with improved stability and selective toxicity to bacteria over mammalian cells , 2017, Medical Microbiology and Immunology.

[9]  Muhammad Saad Khan,et al.  Use of Nanoscale Materials for the Effective Prevention and Extermination of Bacterial Biofilms , 2018, Biotechnology and Bioprocess Engineering.

[10]  Jintae Lee,et al.  Alizarin and Chrysazin Inhibit Biofilm and Hyphal Formation by Candida albicans , 2017, Front. Cell. Infect. Microbiol..

[11]  B. Mishra,et al.  Curcumin Quantum Dots Mediated Degradation of Bacterial Biofilms , 2017, Front. Microbiol..

[12]  M. Bonten,et al.  P. aeruginosa colonization at ICU admission as a risk factor for developing P. aeruginosa ICU pneumonia , 2017, Antimicrobial Resistance & Infection Control.

[13]  E. Combet,et al.  The Anti-Adhesive Effect of Curcumin on Candida albicans Biofilms on Denture Materials , 2017, Front. Microbiol..

[14]  S. K. Rajasekharan,et al.  Antibiofilm and Anti-β-Lactamase Activities of Burdock Root Extract and Chlorogenic Acid against Klebsiella pneumoniae. , 2017, Journal of microbiology and biotechnology.

[15]  I. Rasooli,et al.  Filamentous hemagglutinin adhesin FhaB limits A.baumannii biofilm formation. , 2017, Frontiers in bioscience.

[16]  Jayme L. Dahlin,et al.  The Essential Medicinal Chemistry of Curcumin , 2017, Journal of medicinal chemistry.

[17]  Sheela Chandra,et al.  Flavonoids: an overview , 2016, Journal of Nutritional Science.

[18]  S. Peh,et al.  Antibacterial Action of Curcumin against Staphylococcus aureus: A Brief Review , 2016, Journal of tropical medicine.

[19]  P. Visca,et al.  Acinetobacter baumannii Biofilm Formation in Human Serum and Disruption by Gallium , 2016, Antimicrobial Agents and Chemotherapy.

[20]  J. Hardouin,et al.  Global Dynamic Proteome Study of a Pellicle-forming Acinetobacter baumannii Strain , 2016, Molecular & Cellular Proteomics.

[21]  Yuehua Wu,et al.  Biofilm-Related Genes: Analyses in Multi-Antibiotic Resistant Acinetobacter Baumannii Isolates From Mainland China , 2016, Medical science monitor : international medical journal of experimental and clinical research.

[22]  T. Umland,et al.  The Response Regulator BfmR Is a Potential Drug Target for Acinetobacter baumannii , 2016, mSphere.

[23]  Chuanfu Zhang,et al.  Relationship between Antibiotic Resistance, Biofilm Formation, and Biofilm-Specific Resistance in Acinetobacter baumannii , 2016, Front. Microbiol..

[24]  E. Mylonakis,et al.  Impact of a Cross-Kingdom Signaling Molecule of Candida albicans on Acinetobacter baumannii Physiology , 2015, Antimicrobial Agents and Chemotherapy.

[25]  U. H. Stroeher,et al.  Identification of genes essential for pellicle formation in Acinetobacter baumannii , 2015, BMC Microbiology.

[26]  A. Kumari,et al.  Bactericidal Activity of Curcumin I Is Associated with Damaging of Bacterial Membrane , 2015, PloS one.

[27]  Li-juan Wu,et al.  Enhancing pili assembly and biofilm formation in Acinetobacter baumannii ATCC19606 using non-native acyl-homoserine lactones , 2015, BMC Microbiology.

[28]  N. Høiby,et al.  Strategies for combating bacterial biofilm infections , 2014, International Journal of Oral Science.

[29]  O. Lesouhaitier,et al.  Characterisation of Pellicles Formed by Acinetobacter baumannii at the Air-Liquid Interface , 2014, PloS one.

[30]  S. Ryu,et al.  Stilbenes reduce Staphylococcus aureus hemolysis, biofilm formation, and virulence. , 2014, Foodborne pathogens and disease.

[31]  C. Tang,et al.  The sensor kinase BfmS mediates virulence in Acinetobacter baumannii. , 2014, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[32]  D. Wareham,et al.  In vitro activity of curcumin in combination with epigallocatechin gallate (EGCG) versus multidrug-resistant Acinetobacter baumannii , 2014, BMC Microbiology.

[33]  Rishan Singh Determination of Minimum Inhibitory Concentration of Cycloserine in Multidrug Resistant Mycobacterium tuberculosis Isolates , 2014 .

[34]  G. Allam,et al.  Hesperidin Inhibits Inflammatory Response Induced by Aeromonas hydrophila Infection and Alters CD4+/CD8+ T Cell Ratio , 2014, Mediators of inflammation.

[35]  J. Boyce,et al.  Biological Cost of Different Mechanisms of Colistin Resistance and Their Impact on Virulence in Acinetobacter baumannii , 2013, Antimicrobial Agents and Chemotherapy.

[36]  Sean D. Stowe,et al.  Identification of BfmR, a response regulator involved in biofilm development, as a target for a 2-Aminoimidazole-based antibiofilm agent. , 2012, Biochemistry.

[37]  Jintae Lee,et al.  Flavone Reduces the Production of Virulence Factors, Staphyloxanthin and α-Hemolysin, in Staphylococcusaureus , 2012, Current Microbiology.

[38]  Donoghue,et al.  Acinetobacter baumannii , 2012, Virulence.

[39]  Karl A. Hassan,et al.  Adherence and motility characteristics of clinical Acinetobacter baumannii isolates. , 2011, FEMS microbiology letters.

[40]  Jung-Ae Kim,et al.  Apple Flavonoid Phloretin Inhibits Escherichia coli O157:H7 Biofilm Formation and Ameliorates Colon Inflammation in Rats , 2011, Infection and Immunity.

[41]  R. Bonomo,et al.  Genetic analysis of surface motility in Acinetobacter baumannii. , 2011, Microbiology.

[42]  S. Zinjarde,et al.  Biofilm formation by Acinetobacter baumannii strains isolated from urinary tract infection and urinary catheters. , 2011, FEMS immunology and medical microbiology.

[43]  J. Vila,et al.  Biofilm formation at the solid-liquid and air-liquid interfaces by Acinetobacter species , 2011, BMC Research Notes.

[44]  J. Gaddy,et al.  The Opportunistic Human Pathogen Acinetobacter baumannii Senses and Responds to Light , 2010, Journal of bacteriology.

[45]  W. Bowen,et al.  Inhibitory effects of cranberry polyphenols on formation and acidogenicity of Streptococcus mutans biofilms. , 2006, FEMS microbiology letters.

[46]  L. Actis,et al.  Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: involvement of a novel chaperone-usher pili assembly system. , 2003, Microbiology.

[47]  G. Beecher,et al.  Liquid chromatographic method for the separation and quantification of prominent flavonoid aglycones. , 2000, Journal of chromatography. A.

[48]  J. Costerton,et al.  Bacterial biofilms: a common cause of persistent infections. , 1999, Science.

[49]  A. Schulze,et al.  Plasmid DNA fingerprinting of Acinetobacter species other than Acinetobacter baumannii , 1994, Journal of clinical microbiology.

[50]  Howard C. Berg,et al.  Genetic analysis , 1957, Nature Biotechnology.

[51]  T. Wood,et al.  Repurposing the anticancer drug mitomycin C for the treatment of persistent Acinetobacter baumannii infections. , 2017, International journal of antimicrobial agents.

[52]  M. Bonten,et al.  Staphylococcus aureus colonization at ICU admission as a risk factor for developing S. aureus ICU pneumonia. , 2017, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[53]  Clinical,et al.  Performance standards for antimicrobial disk and dilution susceptibilty tests for bacteria isolated from animals : approved standard , 2008 .

[54]  J. Bryers Bacterial biofilms. , 1993, Current opinion in biotechnology.