This study aimed to develop synergistic
therapies to treat superbug
infections through the encapsulation of
sortase A inhibitors (SrtAIs; trans-
chalcone (TC),
curcumin (CUR),
quercetin (QC), or
berberine chloride (BR)) into
MCM-41 mesoporous
silica nanoparticles (MSNs) or a
phosphonate-modified analogue (MCM-41-PO3-) to overcome their poor aqueous solubility. A
resazurin-modified minimum inhibitory concentration (MIC) and checkerboard assays, to measure SrtAI synergy in combination with leading
antimicrobial peptides (AMPs;
pexiganan (PEX),
indolicidin (INDO), and [I5, R8]
mastoparan (MASTO)), were determined against
methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The results demonstrated that the
MCM-41 and MCM-41-PO3- formulations significantly improved the aqueous solubility of each SrtAI. The MICs for SrtAI/MCM-41-PO3- formulations were lower compared to the SrtAI/MCM-41 formulations against tested bacterial strains, except for the cases of BR/MCM-41 and QC/MCM-41 against P. aeruginosa. Furthermore, the following combinations demonstrated synergy: PEX with TC/MCM-41 (against all strains) or TC/MCM-41-PO3- (against all strains except P. aeruginosa); PEX with BR/MCM-41 or BR/MCM-41-PO3- (against MSSA and MRSA); INDO with QC/MCM-41 or QC/MCM-41-PO3- (against MRSA); and MASTO with CUR/MCM-41 (against E. coli). These combinations also reduced each components' toxicity against human embryonic kidney cells. In conclusion,
MCM-41 MSNs provide a platform to enhance SrtAI solubility and demonstrated antimicrobial synergy with AMPs and reduced toxicity, providing novel superbug treatment opportunities.