Abstract
Multidrug resistant (MDR) methicillin-resistant Staphylococcus aureus (MRSA) is a superbug pathogen that causes serious diseases. One of the main reasons for the lack of the effectiveness of antibiotic therapy against infections caused by this resistant pathogen is the recalcitrant nature of MRSA biofilms, which results in an increasingly serious situation worldwide. Consequently, the development of innovative biofilm inhibitors is urgently needed to control the biofilm formation by this pathogen. In this work, we thus sought to evaluate the biofilm inhibiting ability of some promising antibiofilm agents such as zinc oxide nanoparticles (Zno NPs), proteinase K, and hamamelitannin (HAM) in managing the MRSA biofilms. Different phenotypic and genotypic methods were used to identify the biofilm producing MDR MRSA isolates and the antibiofilm/antimicrobial activities of the used promising agents. Our study demonstrated strong antibiofilm activities of ZnO NPs, proteinase K, and HAM against MRSA biofilms along with their transcriptional modulation of biofilm (intercellular adhesion A, icaA) and quorum sensing (QS) (agr) genes. Interestingly, only ZnO NPs showed a powerful antimicrobial activity against this pathogen. Collectively, we observed overall positive correlations between the biofilm production and the antimicrobial resistance/agr genotypes II and IV. Meanwhile, there was no significant correlation between the toxin genes and the biofilm production. The ZnO NPs were recommended to be used alone as potent antimicrobial and antibiofilm agents against MDR MRSA and their biofilm-associated diseases. On the other hand, proteinase-K and HAM can be co-administrated with other antimicrobial agents to manage such types of infections.
Highlights
Staphylococcus aureus (S. aureus) is a widely distributed pathogen responsible for a variety of disease conditions
Correlation analyses used to unravel the extent of association between biofilm production ability and antimicrobial resistances, toxin genes, and agr genotypes revealed that there was no significant correlation between biofilm production and toxin genes
The results revealed that HAM exerted a pronounced antibiofilm activity against biofilm associated methicillin-resistant Staphylococcus aureus (MRSA) isolates with a mean reducing capacity of 99.66%
Summary
Staphylococcus aureus (S. aureus) is a widely distributed pathogen responsible for a variety of disease conditions. It can cause invasive infections in humans and animals with high mortality rates worldwide [1]. Numerous different diseases are associated with S. aureus infection. This has been attributed to the expression of a large repertoire of virulence genes such as coagulase (coa), S. aureus protein A (spa), Panton–Valentine leucocidin (pvl), toxic shock syndrome toxin (tst), exfoliative toxins A (eta) and B (etb), and staphylococcal enterotoxins A–G (sea–seg), which cause harmful toxic effects to the host [2,3]. The agr system increases the production of many virulence factors and decreases the expression of several colonization factors under conditions of high cell density
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