Abstract
Multidrug-resistant pathogens causing nosocomial and community acquired infections delineate a significant threat to public health. It had urged to identify new antimicrobials and thus, generated interest in studying macrocyclic metal complex, which has been studied in the past for their antimicrobial activity. Hence, in the present study, we have evaluated the antimicrobial activity of the hexadentated macrocyclic complex of copper (II) (Cu Complex) derived from thiosemicarbazide against Gram-positive and Gram-negative bacteria. We observed increased susceptibility against standard isolates of Staphylococcus aureus with a minimum inhibitory concentration (MIC) range of 6.25 to 12.5 μg/mL. Similar activity was also observed towards methicillin resistant and sensitive clinical isolates of S. aureus from human (n = 20) and animal (n = 20) infections. The compound has rapid bactericidal activity, and we did not observe any resistant mutant of S. aureus. The compound also exhibited antibiofilm activity and was able to disrupt pre-formed biofilms. Cu complex showed increased susceptibility towards intracellular S. aureus and was able to reduce more than 95% of the bacterial load at 10 μg/mL. Overall, our results suggest that Cu complex with its potent anti-microbial and anti-biofilm activity can be used to treat MRSA infections and evaluated further clinically.
Highlights
Antimicrobial resistance (AMR) has emerged as a global threat to public health and have become the leading cause of mortality
Antibacterial activity of the Cu complex was evaluated against Gram-negative (Pseudomonas aeruginosa, Acinetobacter baumanii, Klebsiella pneumonia, and Escherichia coli) and Gram-positive (Staphylococcus aureus, Clostridium difficile and Enterococcus faecalis) bacteria (Table 1)
Antimicrobial activity was observed against methicillin resistant and sensitive (MRSA & MSSA) isolates of S. aureus, which showed minimum inhibitory concentration (MIC) ranged from 6.25 to 12.5 μg/mL) (Fig. 2)
Summary
Antimicrobial resistance (AMR) has emerged as a global threat to public health and have become the leading cause of mortality. Methicillin-resistant S. aureus (MRSA) is solely responsible for many life-threatening nosocomial infections in humans which increases the treatment duration and medical costs[3,4]. They are known to cause several mild to chronic infection in animals. Biofilms are challenging to treat and considered as a bacterial reservoir for dissemination to various body sites[8,10] These infections may result in the replacement of the implanted medical device, thereby causing increased distress with additional medical costs to the patient[10,11,12]. The primary aim of our study is to determine the antibacterial activity of the Cu complex against clinically important bacterial pathogens and to investigate their mechanism of action, antibacterial and antibiofilm efficacy and capacity to kill intracellular bacteria
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