Antimicrobial Activity of Arthrospira platensis-Mediated Gold Nanoparticles against Streptococcus pneumoniae: A Metabolomic and Docking Study

Abstract

The emergence of antibiotic-resistant Streptococcus pneumoniae necessitates the discovery of novel therapeutic agents. This study investigated the antimicrobial potential of green-synthesized gold nanoparticles (AuNPs) fabricated using Arthrospira platensis extract. Characterization using Fourier transform infrared spectroscopy revealed the presence of functional groups such as ketones, aldehydes, and carboxylic acids in the capping agents, suggesting their role in AuNP stabilization. Transmission electron microscopy demonstrated the formation of rod-shaped AuNPs with a mean diameter of 134.8 nm, as determined by dynamic light scattering, and a zeta potential of -27.2 mV, indicating good colloidal stability. The synthesized AuNPs exhibited potent antibacterial activity against S. pneumoniae, with a minimum inhibitory concentration (MIC) of 12 μg/mL, surpassing the efficacy of the control antibiotic, tigecycline. To elucidate the underlying mechanisms of action, an untargeted metabolomic analysis of the A. platensis extract was performed, identifying 26 potential bioactive compounds belonging to diverse chemical classes. In silico studies focused on molecular docking simulations revealed that compound 22 exhibited a strong binding affinity to S. pneumoniae topoisomerase IV, a critical enzyme for bacterial DNA replication. Molecular dynamics simulations further validated the stability of this protein-ligand complex. These findings collectively highlight the promising antimicrobial potential of A. platensis-derived AuNPs and their constituent compounds, warranting further investigation for the development of novel anti-pneumococcal therapeutics.

Keywords: Arthrospira platensis; Streptococcus pneumoniae; antimicrobial; gold nanoparticles; metabolics; molecular docking; protein-protein interaction.

Figure 1

(A) UV-Vis spectral analysis of biosynthesized AuNPs using A. platensis methanolic extract. (B) FTIR spectra of the biosynthesized AuNPs.

Figure 2

(A) TEM analysis showing the shape and size of synthesized AuNPs using A. platensis methanolic extract. (B) The histogram illustrates the size distribution of the synthesized AuNPs.

Figure 3

(A) Dynamic light scattering analysis of the synthesized AuNPs of A. platensis methanolic extract, and (B) Zeta potential analysis of the synthesized AuNPs of A. platensis methanolic extract.

Figure 4

Chemical structures of identified metabolites in A. platensis extract as detected in LC–MS total ion chromatogram.

Figure 5

Total ion chromatograms (TIC) of A. platensis extract in (A) negative and (B) positive following analysis by ultra-performance liquid chromatography–tandem mass spectrometry.

Figure 6

STITCH analysis of S. pneumoniae targets and key active compounds in A. platensis extract.

Figure 7

PPI network for A. platensis extract against S. pneumoniae infections. The nodes represent various proteins involved in biological processes related to the immune response, cell signaling, apoptosis, and metabolic regulation. The color coding of the nodes indicates their functional categories: Red for apoptosis regulators, Green for immune response proteins, Blue for cell signaling proteins, Purple for metabolic enzymes, Yellow for inflammatory response proteins, Orange for transcription regulators, and Pink for proteins involved in cell proliferation and growth.

Figure 8

Bubble chart illustrating gene ontology classifications for the antibacterial properties of A. platensis extract against S. pneumoniae: biological process, cellular component, and molecular function.

Figure 9

Bar plot illustrating the significant KEGG pathways enriched by A. platensis extract, showcasing their potential antibacterial effects against S. pneumoniae.

Figure 10

Th17 cell differentiation pathway illustrating how A. platensis extract modulates immune responses to combat S. pneumoniae infections. Solid lines represent direct interactions or activation steps in the signaling pathways, while dashed lines indicate indirect interactions, regulatory effects, or transcriptional regulation.

Figure 11

Key hub genes identified in the PPI network related to the antibacterial effects of A. platensis extract against S. pneumoniae.

Figure 12

Binding interactions with topoisomerase IV of S. pneumoniae. (A) interaction map of compound 22 highlighting the conventional hydrogen bonds and alkyl interactions. (B) interaction map of Levofloxacin.

Figure 13

RMSD analysis of topoisomerase IV complexed with compound 22 (blue line) and Levofloxacin (red line) over 150 ns of molecular dynamics simulation.

Figure 14

Radius of gyration (Rg) analysis of topoisomerase IV complexed with compound 22 (blue line) and Levofloxacin (red line) over 150 ns of molecular dynamics simulation.

Figure 15

Potential energy analysis of topoisomerase IV complexed with compound 22 (blue line) and Levofloxacin (red line) over 150 ns of molecular dynamics simulation.