Tackling strong biofilm and multi-virulent vancomycin-resistant Staphylococcus aureus via natural alkaloid-based porous nanoparticles: perspective towards near future eradication

Marwa I Abd El-Hamid; Doaa Ibrahim; Sara T Elazab; Wafaa M Gad; Marwa Shalaby; Wafaa M El-Neshwy; Mohammed Abdulrahman Alshahrani; Ahmed Saif; Reem M Algendy; Maha AlHarbi; Fayez M Saleh; Afaf Alharthi; Eman A A Mohamed

doi:10.3389/fcimb.2023.1287426

Tackling strong biofilm and multi-virulent vancomycin-resistant Staphylococcus aureus via natural alkaloid-based porous nanoparticles: perspective towards near future eradication

Front Cell Infect Microbiol. 2024 Jan 12:13:1287426. doi: 10.3389/fcimb.2023.1287426. eCollection 2023.

Authors

Affiliations

¹ Department of Microbiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
² Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
³ Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
⁴ Department of Bacteriology, Animal Health Research Institute (AHRI), Mansoura Branch, Agriculture Research Center, Mansoura, Egypt.
⁵ Department of Animal Medicine, Infectious Diseases, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
⁶ Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, Najran, Saudi Arabia.
⁷ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
⁸ Food Hygiene, Safety and Technology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
⁹ Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
¹⁰ Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia.
¹¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.

Abstract

Introduction: As a growing direction, nano-based therapy has become a successful paradigm used to address the phytogenic delivery-related problems in overcoming multivirulent vancomycin-resistant Staphylococcus aureus (VRSA) infection.

Methods: Hence, our aim was to develop and assess a novel nanocarrier system (mesoporous silica nanoparticles, MPS-NPs) for free berberine (Free-BR) as an antimicrobial alkaloid against strong biofilm-producing and multi-virulent VRSA strains using in vitro and in vivo mouse model.

Results and discussion: Our outcomes demonstrated vancomycin resistance in 13.7% of Staphylococcus aureus (S. aureus) strains categorized as VRSA. Notably, strong biofilm formation was observed in 69.2% of VRSA strains that were all positive for icaA gene. All strong biofilm-producing VRSA strains harbored a minimum of two virulence genes comprising clfA and icaA with 44.4% of them possessing all five virulence genes (icaA, tst, clfA, hla, and pvl), and 88.9% being multi-virulent. The study findings affirmed excellent in vitro antimicrobial and antibiofilm properties of BR-loaded MPS-NPs. Real-time quantitative reverse transcription PCR (qRT-PCR) assay displayed the downregulating role of BR-loaded MPS-NPs on strong biofilm-producing and multi-virulent VRSA strains virulence and agr genes in both in vitro and in vivo mice models. Additionally, BR-loaded MPS-NPs supplementation has a promising role in attenuating the upregulated expression of pro-inflammatory cytokines' genes in VRSA-infected mice with attenuation in pro-apoptotic genes expression resulting in reduced VRSA-induced apoptosis. In essence, the current study recommends the future scope of using BR-loaded MPS-NPs as auspicious alternatives for antimicrobials with tremendous antimicrobial, antibiofilm, anti-quorum sensing (QS), and anti-virulence effectiveness against problematic strong biofilm-producing and multi-virulent VRSA-associated infections.

Keywords: QS; VRSA; biofilm; inflammation; multi-virulent; nanoparticles; natural alkaloids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkaloids* / pharmacology
Animals
Anti-Bacterial Agents / pharmacology
Biofilms
Methicillin-Resistant Staphylococcus aureus* / genetics
Mice
Microbial Sensitivity Tests
Nanoparticles*
Porosity
Staphylococcal Infections* / drug therapy
Staphylococcus aureus
Vancomycin-Resistant Staphylococcus aureus

Substances

Anti-Bacterial Agents
Alkaloids

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The research was funded by the Princess Nourah bint Abdulrahman University Researchers Supporting Project with number PNURSP2023R182, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.