1 research outputs found
A Highly Potent Antibacterial Agent Targeting Methicillin-Resistant Staphylococcus aureus Based on Cobalt Bis(1,2-Dicarbollide) Alkoxy Derivative
Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious superbug
that is potentially life-threatening.
Among conventional antibiotics, vancomycin is a āgold standardā
agent used to treat serious MRSA infections. Such therapy, however,
is often ineffective because of the emergence of less-susceptible
strains. Therefore, the exploration of new antimicrobial agents, especially
nonantibiotic drugs, to cope with the growing threat of MRSA has become
an urgent necessity. Herein, we have investigated the possibility
to develop a metallacarborane antimicrobial agent, cobalt bisĀ(1,2-dicarbollide)
alkoxy derivative (K121), and we have evaluated the relevant anti-MRSA
behaviors. We demonstrated that K121 has a dose-dependent anti-MRSA
activity with a low minimal inhibitory concentration of 8 Ī¼g/mL
and a high selectivity over mammalian cells. In particular, a high
bacteria-killing efficiency was observed with eradication of all MRSA
cells within 30 min. In addition, K121 showed a high inhibition effect
on the formation of bacterial biofilm. More importantly, unlike vancomycin,
a repeated use of K121 would not induce drug resistance even after
20 passages of MRSA. The mechanistic study showed that K121 kills
MRSA by inducing an increase in the reactive oxygen species (ROS)
production and consequentially inducing irreversible damage to the
cell wall/membrane, which ultimately leads to the death of MRSA. Our
results suggested that K121 may be used as a promising nonantibiotic
therapeutic agent against MRSA infections in future clinical practices