Promising Antibiofilm Agents: Recent Breakthrough against Biofilm Producing Methicillin-Resistant Staphylococcus aureus

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.

Keywords: HAM; MRSA; ZnO-NPs; antibiofilm; antimicrobial; proteinase-K.

Figure 1

Antimicrobial resistance of biofilm producing methicillin-resistant Staphylococcus aureus isolates from different sources. DA: clindamycin; CN: gentamicin; VA: vancomycin; FOX: cefoxitin; CRO: ceftriaxone; IPM: imipenem; ME: methicillin; AMC: amoxicillin-clavulanic acid; RF: rifamycin SV; C: chloramphenicol; E: erythromycin; SXT: trimethoprim-sulfamethoxazole; CIP: ciprofloxacin.

Figure 2

Correlation between biofilm production and antimicrobial resistance, toxin genes, and agr genotypes of methicillin-resistant Staphylococcus aureus isolates. VA: vancomycin; IPM: imipenem; DA: clindamycin; C: chloramphenicol; RF: rifamycin SV; E: erythromycin; SXT: trimethoprim-sulfamethoxazole; AMC: amoxicillin-clavulanic acid; CRO: ceftriaxone; CN: gentamicin; CIP: ciprofloxacin; agr: accessory gene regulator; pvl: Panton-Valentine leucocidin; sea, see and sec: staphylococcal enterotoxins A, B and C; tst: toxic shock syndrome toxin; eta and etb: exfoliative toxins A and B; * above the columns indicate significant differences (p < 0.05).

Figure 3

Fold changes in the expression of icaA and agr genes for all biofilm producing isolates post exposure to ZnO NPs, HAM, and proteinase K. agr: accessory gene regulator; icaA: intercellular adhesion A gene; ZnO NPs: zinc oxide nanoparticles; HAM: hamamelitannin.