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The Activity of Gold Nanoparticles Synthesized Using Helichrysum odoratissimum Against Cutibacterium acnes Biofilms.

ABSTRACT: The human skin is home to millions of bacteria, fungi, and viruses which form part of a unique microbiome. Commensal microbes, including Cutibacterium acnes can occasionally become opportunistic resulting in the onset of dermatological diseases such as acne. Acne is defined as a chronic inflammatory disorder based on its ability to persist for long periods throughout an individual's life. The synthesis of gold nanoparticles (AuNPs) was performed using the bottom-up approach by reduction of a gold salt (HAuCl₄.3H₂O) by the methanol extract (HO-MeOH) and aqueous decoction prepared from the dried aerial parts of Helichrysum odoratissimum (HO-Powder). The HO-MeOH and HO-Powder AuNPs were prepared as unstabilised (-GA) or stabilized (+GA) by the omission or addition of Gum Arabic (GA) as the capping agent. The characterization of the AuNPs was performed using Transmission Electron Microscopy (TEM), dynamic light scattering (DLS), Ultraviolet-Visual spectroscopy (UV-Vis), Thermogravimetric Analysis (TGA), X-Ray Diffraction (XRD) and Zeta-potential. The MBIC₅₀ values for HO-MeOH - GA and HO-MeOH + GA were 1.79 ± 0.78% v/v and 0.22 ± 0.16% v/v, respectively. The HO-Powder AuNPs showed potent inhibition of C. acnes cell adhesion to the 96-well plates. The HO-MeOH - GA and HO-Powder + GA exhibited IC₅₀ of 22.01 ± 6.13% v/v and 11.78 ± 1.78% v/v, respectively. The activity of the AuNPs validated the anti-adhesion activity of the methanol extract in the crude form. The study emphasizes the selectivity of H. odoratissimum AuNPs for the prevention of C. acnes cell adhesion and not antimicrobial activity, which may prevent the emergence of resistant strains of C. acnes through reduced bactericidal or bacteriostatic activity, while targeting mechanisms of pathogenesis.

SUBMITTER: De Canha MN

PROVIDER: S-EPMC8473823 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The Gram-positive bacterium Cutibacterium acnes (previously Propionibacterium acnes), plays an important role in the pathogenesis and progression of the dermatological skin disorder acne vulgaris. The methanolic extract of Helichrysum odoratissimum (L.) Sweet (HO-MeOH) was investigated for its ability to target bacterial growth and pathogenic virulence factors associated with acne progression. The gas chromatography-mass spectrometry (GC-MS) analysis of HO-MeOH identified α-humulene (3.94%), α-curcumene (3.74%), and caryophyllene (8.12%) as major constituents, which correlated with previous reports of other Helichrysum species. The HO-MeOH extract exhibited potent antimicrobial activity against C. acnes (ATCC 6919) with a minimum inhibitory concentration (MIC) of 7.81 µg/ml. It enhanced the antimicrobial activity of benzoyl peroxide (BPO). The extract showed high specificity against C. acnes cell aggregation at sub-inhibitory concentrations, preventing biofilm formation. Mature C. acnes biofilms were disrupted at a sub-inhibitory concentration of 3.91 µg/ml. At 100 µg/ml, HO-MeOH reduced interleukin-1α (IL-1α) cytokine levels in C. acnes-induced human keratinocytes (HaCaT) by 11.08%, highlighting its potential as a comedolytic agent for the treatment of comedonal acne. The extract exhibited a 50% inhibitory concentration (IC50) of 157.50 µg/ml against lipase enzyme activity, an enzyme responsible for sebum degradation, ultimately causing inflammation. The extract's anti-inflammatory activity was tested against various targets associated with inflammatory activation by the bacterium. The extract inhibited pro-inflammatory cytokine levels of IL-8 by 48.31% when compared to C. acnes-induced HaCaT cells at 7.81 µg/ml. It exhibited cyclooxygenase-II (COX-II) enzyme inhibition with an IC50 of 22.87 µg/ml. Intracellular nitric oxide (NO) was inhibited by 40.39% at 7.81 µg/ml when compared with NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The intracellular NO inhibition was potentially due to the 2.14 fold reduction of inducible nitric oxide synthase (iNOS) gene expression. The HO-MeOH extract exhibited an IC50 of 145.45 µg/ml against virulent hyaluronidase enzyme activity, which is responsible for hyaluronan degradation and scar formation. This study provides scientific validation for the traditional use of H. odoratissimum as an ointment for pimples, not only due to its ability to control C. acnes proliferation but also due to its inhibitory activity on various targets associated with bacterial virulence leading to acne progression.

Project description:Cutibacterium acnes is a human skin-resident bacterium. Although C. acnes maintains skin health by inhibiting invasion from pathogens like Staphylococcus aureus, it also contributes to several diseases, including acne. Studies suggest that differences in genetic background may explain the diverse phenotypes of C. acnes strains. In this study, we investigated the effects of C. acnes strains on the Caenorhabditis elegans life span and observed that some strains shortened the life span, whereas other strains, such as strain HL110PA4, did not alter it. Next, we assessed the effects of C. acnes HL110PA4 on host resistance against S. aureus. The survival time of C. acnes HL110PA4-fed wild-type animals was significantly longer than that of Escherichia coli OP50 control bacterium-fed worms upon infection with S. aureus. Although the survival times of worms harboring mutations at the daf-16/FoxO and skn-1/Nrf2 loci were similar to those of wild-type worms after S. aureus infection, administration of C. acnes failed to improve survival times of tir-1/SARM1, nsy-1/mitogen-activated protein kinase kinase kinase (MAPKKK), sek-1/mitogen-activated protein kinase kinase (MAPKK), and pmk-1/p38 mitogen-activated protein kinase (MAPK) mutants. These results suggest that the TIR-1 and p38 MAPK pathways are involved in conferring host resistance against S. aureus in a C. acnes-mediated manner. IMPORTANCE Cutibacterium acnes is one of the most common bacterial species residing on the human skin. Although the pathogenic properties of C. acnes, such as its association with acne vulgaris, have been widely described, its beneficial aspects have not been well characterized. Our study classifies C. acnes strains based on its pathogenic potential toward the model host C. elegans and reveals that the life span of C. elegans worms fed on C. acnes was consistent with the clinical association of C. acnes ribotypes with acne or nonacne. Furthermore, nonpathogenic C. acnes confers host resistance against the opportunistic pathogen Staphylococcus aureus. Our study provides insights into the impact of C. acnes on the host immune system and its potential roles in the ecosystem of skin microbiota.

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The Activity of Gold Nanoparticles Synthesized Using Helichrysum odoratissimum Against Cutibacterium acnes Biofilms.

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