Aminoglycosides with Anti-MRSA Activity: A Concise Review

Abstract

: Methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of infections in human being and is usually associated with a multidrug-resistant profile, represents a significant health threat and public burden globally. The limited options of effective antibiotics motivate the search for novel anti-MRSA agents. Aminoglycoside antibiotics have been extensively applied in the medical field due to their desirable broad-spectrum antibacterial activity, especially for systemic infections caused by Gram-negative organisms. Recent studies demonstrated that aminoglycosides also possessed potential activity against MRSA, so aminoglycosides may be useful weapons to fight against MRSA. The present work aims to summarize the current scenario of aminoglycosides with anti-MRSA potential, covering articles published between 2010 and 2020. The structure-activity relationship and the mechanism of action are also discussed for the further rational design of novel potential drug candidates.

Nickel Nanoparticles: Applications and Antimicrobial Role against Methicillin-Resistant Staphylococcus aureus Infections

“…Natural combination therapies using Polysporin and Neosporin peptides have also exerted anti-MRSA effects [ 47 ]. Major chemotherapy approaches to combat MRSA have included telavancin, teicoplanin, ceftaroline, vancomycin, and oxazolidinones [ 48 , 49 ]. The combination of β-lactam and either arbekacin or vancomycin is recommended against MRSA.…”

Proteomic assay for rapid characterization ofStaphylococcus aureusantimicrobial resistance directly from blood cultures

“…Resistance toward these molecules are caused by the acquisition of aminoglycoside modifying enzymes (AMEs), which can inactivate antibiotics through the addition of a chemical group to the aminoglycoside backbone. In S. aureus, the most important AMEs are: (i) the APH(2")), encoded by the aac(6')-Ie-aph(2")-Ia gene, confers resistance to gentamicin, tobramycin, kanamycin, amikacin and neomycin (11)(12)(13)(14)(15).…”

“…Resistance toward these molecules are caused by the acquisition of aminoglycoside modifying enzymes (AMEs), which can inactivate antibiotics through the addition of a chemical group to the aminoglycoside backbone. In S. aureus , the most important AMEs are: (i) the 3’-O-phosphotransferase III (APH(3’)-III), encoded by the aph(3’)-IIIa gene, inactivates kanamycin and amikacin; (ii) the 4’-Oadenyltransferase I (ANT(4’)-I), encoded by the ant(4’)-Ia gene, inactivates kanamycin, neomycin, tobramycin and amikacin; and (iii) the 6’-N-acetyltransferase-2"O-phosphotransferase (AAC(6’)-APH(2")), encoded by the aac(6’)-Ie-aph(2")-Ia gene, confers resistance to gentamicin, tobramycin, kanamycin, amikacin and neomycin (11–15).…”

The effect of selected aminoglycoside antibiotics on human serum albumin antioxidant activity: a spectroscopic and calorimetric comparative study

“…Due to the broad spectrum of antibacterial activity, rapid bactericidal speed, and the possibility of chemical modification to amphiphilic aminoglycosides, they are important from the pharmacology research perspective [ 18 , 19 ]. Aminoglycosides are antibacterial agents with a broad spectrum of actions that disrupt protein translation on prokaryotic ribosomes (70S) [ 18 , 20 , 21 ] and are used for the treatment of infections caused by the Enterobacteriaceae family, as well as Francisella tularensis , Yersinia pestis , Staphylococcus aureus , and Pseudomonas aeruginosa [ 18 – 20 ]. Nevertheless, aminoglycosides are drugs with a narrow therapeutic window and they cause severe and often irreversible side effects, especially nephrotoxicity and ototoxicity [ 21 , 22 ].…”