The Anticancer Agent 3,3'-Diindolylmethane Inhibits Multispecies Biofilm Formation by Acne-Causing Bacteria and Candida albicans

Kim, Yong‐Guy; Lee, Jin-Hyung; Park, Sunyoung

doi:10.1128/spectrum.02056-21

Cited by 22 publications

(23 citation statements)

References 46 publications

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“…Although DIM has been shown to effectively limit larval settlement, providing an antifoulant effect in the marine environment [ 91 ], to the best of our knowledge, our study is the first to show the anti-biofilm activity and virulence attenuation of the agent against Gram-negative bacteria. Moreover, a recent study showed that DIM has antibiofilm activity on Candida albicans and acne-causing bacteria [ 92 ]. Based on its anti-biofilm properties, which affect diverse strains of bacteria, the results of this study suggest that DIM is potentially suitable for attenuating a wide range of bacterial infections.…”

Section: Discussionmentioning

confidence: 99%

Anti-Virulence Activity of 3,3′-Diindolylmethane (DIM): A Bioactive Cruciferous Phytochemical with Accelerated Wound Healing Benefits

et al. 2022

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Antimicrobial resistance is among the top global health problems with antibacterial resistance currently representing the major threat both in terms of occurrence and complexity. One reason current treatments of bacterial diseases are ineffective is the occurrence of protective and resistant biofilm structures. Phytochemicals are currently being reviewed for newer anti-virulence agents. In the present study, we aimed to investigate the anti-virulence activity of 3,3′-diindolylmethane (DIM), a bioactive cruciferous phytochemical. Using a series of in vitro assays on major Gram-negative pathogens, including transcriptomic analysis, and in vivo porcine wound studies as well as in silico experiments, we show that DIM has anti-biofilm activity. Following DIM treatment, our findings show that biofilm formation of two of the most prioritized bacterial pathogens Acinetobacter baumannii and Pseudomonas aeruginosa was inhibited respectively by 65% and 70%. Combining the antibiotic tobramycin with DIM enabled a high inhibition (94%) of P. aeruginosa biofilm. A DIM-based formulation, evaluated for its wound-healing efficacy on P. aeruginosa-infected wounds, showed a reduction in its bacterial bioburden, and wound size. RNA-seq was used to evaluate the molecular mechanism underlying the bacterial response to DIM. The gene expression profile encompassed shifts in virulence and biofilm-associated genes. A network regulation analysis showed the downregulation of 14 virulence-associated super-regulators. Quantitative real-time PCR verified and supported the transcriptomic results. Molecular docking and interaction profiling indicate that DIM can be accommodated in the autoinducer- or DNA-binding pockets of the virulence regulators making multiple non-covalent interactions with the key residues that are involved in ligand binding. DIM treatment prevented biofilm formation and destroyed existing biofilm without affecting microbial death rates. This study provides evidence for bacterial virulence attenuation by DIM.

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Section: Discussionmentioning

confidence: 99%

Anti-Virulence Activity of 3,3′-Diindolylmethane (DIM): A Bioactive Cruciferous Phytochemical with Accelerated Wound Healing Benefits

et al. 2022

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“…Furthermore, alizarin also suppressed the expression of hyaluronate lyase ( hly ; a putative virulence factor), which is capable of destroying the epidermal extracellular matrix and might promote inflammation spread [ 2 ]. Interestingly, it was recently reported that 3,3′-diindolylmethane (an antibiofilm agent) downregulated the expressions of PPA1796, PPA2105, and hly in C. acnes [ 37 ]. Alizarin has also been reported to downregulate two adhesin and two invasion-related genes [ 1 ] and PPA1715 but not to affect the expressions of two other adhesins (PPA1983 and PPA1906) [ 38 ], which suggests that alizarin might inhibit the attachment to and the invasion of host tissue.…”

Section: Discussionmentioning

confidence: 99%

Phytopigment Alizarin Inhibits Multispecies Biofilm Development by Cutibacterium acnes, Staphylococcus aureus, and Candida albicans

et al. 2022

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Acne vulgaris is a common chronic inflammatory skin disease involving Cutibacterium acnes with other skin commensals such as Staphylococcus aureus and Candida albicans in the anaerobic and lipid-rich conditions of pilosebaceous units. These microbes readily form multispecies biofilms that are tolerant of traditional antibiotics as well as host immune systems. The phytopigment alizarin was previously found to prevent biofilm formation by S. aureus and C. albicans strains under aerobic conditions. Hence, we hypothesized that alizarin might control C. acnes and multispecies biofilm development. We found that under anaerobic conditions, alizarin efficiently inhibited single biofilm formation and multispecies biofilm development by C. acnes, S. aureus, and C. albicans without inhibiting planktonic cell growth. Alizarin increased the hydrophilicities of S. aureus and C. albicans cells, decreased lipase production by S. aureus, diminished agglutination by C. acnes, and inhibited the aggregation of C. albicans cells. Furthermore, the co-administration of alizarin and antibiotics enhanced the antibiofilm efficacies of alizarin against C. acnes. A transcriptomic study showed that alizarin repressed the transcriptions of various biofilm-related genes such as lipase, hyaluronate lyase, adhesin/invasion-related, and virulence-related genes of C. acnes. Furthermore, alizarin at 100 µg/mL prevented C. acnes biofilm development on porcine skin. Our results show that alizarin inhibits multispecies biofilm development by acne-causing microbes and suggest it might be a useful agent for treating or preventing C. acnes-causing skin diseases.

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“…Fungi and bacteria are the most common causes of UTI. A single species infection was generally treated with existing antimicrobials, but the polymicrobial cultures are recalcitrance to conventional treatments (Kim et al, 2022;Orazi & O'Toole, 2019;Raj et al, 2022). Therefore, we initially examined the inhibitory activity of BcN16E in killing the planktonic cells was analysed by fluorescence bioimaging.…”

Section: Discussionmentioning

confidence: 99%

Phytolectin conjugated positively charged fatty acid amide impairs virulence factors and inhibits cross-kingdom biofilm formation of Candida albicans and uropathogenic Escherichia coli

Subramaniyan

Ameen

Singaravelu

et al. 2022

Journal of Applied Microbiology

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Aim Polymicrobial biofilm encasing cross‐kingdom micro‐organisms are apparent in medicine, which imposes serious resistance to conventional antimicrobial treatment. The objective of the study was to explore Butea monosperma seed lectin (BMSL) conjugated antimicrobial lipid, 2‐((N‐[2‐hydroxyethyl]palmitamido)methyl)‐1‐methylpyridin‐1‐ium iodide (cN16E) to inhibit mixed‐species biofilm of uropathogenic Escherichia coli–Candida albicans. Methods and Results Antimicrobial activity and antibiofilm of cN16E and cN16E‐BMSL conjugate (BcN16E) were analysed against single‐ and mixed microbial cultures. The minimum inhibitory concentration (MIC) indicates that the MIC of cN16E‐BMSL conjugate (BcN16E) against cohabiting UPEC‐C. albicans was eightfold lower than the cN16E. BcN16E affects membrane integrity to elicit antimicrobial activity. BcN16E inhibits the dual‐species biofilm even with 16 times lower MIC of cN16E. BcN16E impairs the biofilm‐associated virulence factors which include extracellular polysaccharides, cell surface hydrophobicity, swimming, swarming motilities, hyphal filamentous morphology, curli formation and haemolysin activity. As a proof of concept, we demonstrated BcN16E ability to inhibit dual‐species biofilm formation on a urinary catheter. Conclusion The study revealed that the BcN16E is better than cN16E in impairing biofilm‐associated virulence factors and exerting antimicrobial activity. Significance and Impact of the Study The findings emphasize that phytolectin has the potential to enhance the anti‐virulence strategies of antimicrobials against cross‐kingdom biofilm‐related infections.

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The Anticancer Agent 3,3'-Diindolylmethane Inhibits Multispecies Biofilm Formation by Acne-Causing Bacteria and Candida albicans

Cited by 22 publications

References 46 publications

Anti-Virulence Activity of 3,3′-Diindolylmethane (DIM): A Bioactive Cruciferous Phytochemical with Accelerated Wound Healing Benefits

Anti-Virulence Activity of 3,3′-Diindolylmethane (DIM): A Bioactive Cruciferous Phytochemical with Accelerated Wound Healing Benefits

Phytopigment Alizarin Inhibits Multispecies Biofilm Development by Cutibacterium acnes, Staphylococcus aureus, and Candida albicans

Phytolectin conjugated positively charged fatty acid amide impairs virulence factors and inhibits cross-kingdom biofilm formation of Candida albicans and uropathogenic Escherichia coli

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