Novel Insights into the Antimicrobial and Antibiofilm Activity of Pyrroloquinoline Quinone (PQQ); In Vitro , In Silico , and Shotgun Proteomic Studies

Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a...

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Published in:	Biomolecules (Basel, Switzerland) Vol. 14; no. 8; p. 1018
Main Authors:	Labib, Mai M, Alqahtani, Alaa M, Abo Nahas, Hebatallah H, Aldossari, Rana M, Almiman, Bandar Fahad, Ayman Alnumaani, Sarah, El-Nablaway, Mohammad, Al-Olayan, Ebtesam, Alsunbul, Maha, Saied, Essa M
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 01-08-2024 MDPI
Subjects:	Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Anti-Infective Agents - chemistry Anti-Infective Agents - pharmacology Antibacterial activity antibiofilm activity Antibiotics Antifungal activity Antifungal agents Antifungal Agents - chemistry Antifungal Agents - pharmacology Antimicrobial activity Antimicrobial agents Bacteria Bacterial infections Biofilms Biofilms - drug effects Cell membranes Cellular biology Cellular stress response Computer Simulation COVID-19 Disease transmission DNA repair Drug resistance E coli Endonuclease Flexibility Fungal infections Fungi Fungi - drug effects Gram-negative bacteria Gram-Negative Bacteria - drug effects Gram-positive bacteria Gram-Positive Bacteria - drug effects Medical research Membrane proteins Metabolism Methicillin Microbial Sensitivity Tests Microorganisms Minimum inhibitory concentration Molecular Docking Simulation Molecular modelling MRSA Performance evaluation Physiological aspects PQQ Cofactor - chemistry PQQ Cofactor - pharmacology Protein binding Proteomics Public health Pyrroloquinoline quinone R&D Research & development Staphylococcus epidermidis Staphylococcus infections Strains (organisms) Streptococcus infections Transmission electron microscopy Tropical diseases Saudi Arabia Germany antibacterial activity pyrroloquinoline quinone TEM analysis antimicrobial agents molecular modeling MRSA shotgun proteomic analysis antifungal activity antibiofilm activity
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Summary:	Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against , , , and . The MIC values varied between fungal strains, and exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against , , and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, , and strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2218-273X 2218-273X
DOI:	10.3390/biom14081018