Bottger, E. C. & Crich, D. Aminoglycosides: time for the resurrection of a neglected class of antibacterials? ACS Infect. Dis. 6, 168–172 (2020).

Article  CAS  PubMed  Google Scholar 

Ban, Y. H., Song, M. C., Park, J. W. & Yoon, Y. J. Minor components of aminoglycosides: recent advances in their biosynthesis and therapeutic potential. Nat. Prod. Rep. 37, 301–311 (2020).

Article  CAS  PubMed  Google Scholar 

Vicens, Q. & Westhof, E. RNA as a drug target: the case of aminoglycosides. ChemBioChem 4, 1018–1023 (2003).

Article  CAS  PubMed  Google Scholar 

Serio, A. W., Magalhães, M. L., Blanchard, J. S. & Connolly, L. E. A in Antimicrobial Drug Resistance (eds. Mayers, D. L. et al.) 213–229 (Springer, 2017).

Matt, T. et al. Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin. Proc. Natl Acad. Sci. USA 109, 10984–10989 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bassenden, A. V., Rodionov, D., Shi, K. & Berghuis, A. M. Structural analysis of the tobramycin and gentamicin clinical resistome reveals limitations for next-generation aminoglycoside design. ACS Chem. Biol. 11, 1339–1346 (2016).

Article  CAS  PubMed  Google Scholar 

Zárate, S. G. et al. Overcoming aminoglycoside enzymatic resistance: design of novel antibiotics and inhibitors. Molecules 23, 284 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Pfister, P., Hobbie, S., Vicens, Q., Bottger, E. C. & Westhof, E. The molecular basis for A-site mutations conferring aminoglycoside resistance: relationship between ribosomal susceptibility and X-ray crystal structures. ChemBioChem 4, 1078–1088 (2003).

Article  CAS  PubMed  Google Scholar 

Cox, G. et al. Plazomicin retains antibiotic activity against most aminoglycoside modifying enzymes. ACS Infect. Dis. 4, 980–987 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Doi, Y., Wachino, J. I. & Arakawa, Y. Aminoglycoside resistance: the emergence of acquired 16S ribosomal RNA methyltransferases. Infect. Dis. Clin. North Am. 30, 523–537 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Juhas, M. et al. In vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii. J. Antimicrob. Chemother. 74, 944–952 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hu, Y., Liu, L., Zhang, X., Feng, Y. & Zong, Z. In vitro activity of neomycin, streptomycin, paromomycin and apramycin against carbapenem-resistant Enterobacteriaceae clinical strains. Front. Microbiol. 8, 2275 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Ishikawa, M. et al. Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use. Sci. Rep. 9, 2410 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Matsushita, T. et al. Design, multigram synthesis, and in vitro and in vivo evaluation of propylamycin: a semisynthetic 4,5-deoxystreptamine class aminoglycoside for the treatment of drug-resistant Enterobacteriaceae and other Gram-negative pathogens. J. Am. Chem. Soc. 141, 5051–5061 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sati, G. C. et al. Modification at the 2′-position of the 4,5-series of 2-deoxystreptamine aminoglycoside antibiotics to resist aminoglycoside modifying enzymes and increase ribosomal target selectivity. ACS Infect. Dis. 5, 1718–1730 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Plattner, M., Gysin, M., Haldimann, K., Becker, K. & Hobbie, S. N. Epidemiologic, phenotypic, and structural characterization of aminoglycoside-resistance gene aac(3)-IV. Int. J. Mol. Sci. 21, 6133 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Magalhaes, M. L. & Blanchard, J. S. The kinetic mechanism of AAC(3)-IV aminoglycoside acetyltransferase from Escherichia coli. Biochemistry 44, 16275–16283 (2005).

Article  CAS  PubMed  Google Scholar 

Fessler, A. T., Kadlec, K. & Schwarz, S. Novel apramycin resistance gene apmA in bovine and porcine methicillin-resistant Staphylococcus aureus ST398 isolates. Antimicrob. Agents Chemother. 55, 373–375 (2011).

Article  CAS  PubMed  Google Scholar 

Bordeleau, E. et al. ApmA is a unique aminoglycoside antibiotic acetyltransferase that inactivates apramycin. mBio 12, e02705-20 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Quirke, J. C. K. et al. Apralogs: apramycin 5-O-glycosides and ethers with improved antibacterial activity and ribosomal selectivity and reduced susceptibility to the aminoacyltranserferase (3)-IV resistance determinant. J. Am. Chem. Soc. 142, 530–544 (2020).

Article  CAS  PubMed  Google Scholar 

Draker, K. A. & Wright, G. D. Molecular mechanism of the enterococcal aminoglycoside 6′-N-acetyltransferase: role of GNAT-conserved residues in the chemistry of antibiotic inactivation. Biochemistry 43, 446–454 (2004).

Article  CAS  PubMed  Google Scholar 

Stogios, P. J. et al. Potential for reduction of streptogramin A resistance revealed by structural analysis of acetyltransferase VatA. Antimicrob. Agents Chemother. 58, 7083–7092 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Beaman, T. W., Sugantino, M. & Roderick, S. L. Structure of the hexapeptide xenobiotic acetyltransferase from Pseudomonas aeruginosa. Biochemistry 37, 6689–6696 (1998).

Article  CAS  PubMed  Google Scholar 

Murray, I. A. & Shaw, W. V. O-Acetyltransferases for chloramphenicol and other natural products. Antimicrob. Agents Chemother. 41, 1–6 (1997).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Botto, R. E. & Coxon, B. Two-dimensional proton J-resolved NMR spectroscopy of neomycin B. J. Carbohydr. Chem. 3, 545–563 (1984).

Article  CAS  Google Scholar 

Hanessian, S., Takamoto, T., Massé, R. & Patil, G. Aminoglycoside antibiotics: chemical conversion of neomycin B, paromomycin, and lividomycin B into bioactive pseudosaccharides. Can. J. Chem. 56, 1482–1491 (1978).

Article  CAS  Google Scholar 

Eneva, G. I., Spassov, S. L., Haimova, M. A. & Sandström, J. Complete 1H and 13C NMR assignments for apramycin, sisomicin and some N‐ and N, O‐polyacetylated aminoglycosides. Magn. Reson. Chem. 30, 841–846 (1992).

Article  CAS  Google Scholar 

Koshland, D. E. Protein shape and biological control. Sci. Am. 229, 52–67 (1973).

Article  CAS  PubMed  Google Scholar 

Radika, K. & Northrop, D. B. Correlation of antibiotic resistance with Vmax/Km ratio of enzymatic modification of aminoglycosides by kanamycin acetyltransferase. Antimicrob. Agents Chemother. 25, 479–482 (1984).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ellis, J., Bagshaw, C. R. & Shaw, W. V. Substrate binding to chloramphenicol acetyltransferase: evidence for negative cooperativity from equilibrium and kinetic constants for binary and ternary complexes. Biochemistry 30, 10806–10813 (1991).

Article  CAS  PubMed  Google Scholar 

Yoshii, A., Moriyama, H. & Fukuhara, T. The novel kasugamycin 2′-N-acetyltransferase gene aac(2′)-IIa, carried by the IncP island, confers kasugamycin resistance to rice-pathogenic bacteria. Appl. Environ. Microbiol. 78, 5555–5564 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Draker, K. A., Northrop, D. B. & Wright, G. D. Kinetic mechanism of the GC N5-related chromosomal aminoglycoside acetyltransferase AAC(6′)-Ii from Enterococcus faecium: evidence of dimer subunit cooperativity. Biochemistry 42, 6565–6574 (2003).

Article  CAS  PubMed  Google Scholar 

Boehr, D. D., Jenkins, S. I. & Wright, G. D. The molecular basis of the expansive substrate specificity of the antibiotic resistance enzyme aminoglycoside acetyltransferase-6′-aminoglycoside phosphotransferase-2′. The role of Asp-99 as an active site base important for acetyl transfer. J. Biol. Chem. 278, 12873–12880 (2003).

Article  CAS  PubMed  Google Scholar 

Han, Q. et al. Molecular recognition by glycoside pseudo base pairs and triples in an apramycin–RNA complex. Angew. Chem. Int. Ed. Engl. 44, 2694–2700 (2005).

Article  CAS  PubMed  Google Scholar 

Golkar, T. et al. Structural basis for plazomicin antibiotic action and resistance. Commun. Biol. 4, 729 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Walter, F., Vicens, Q. & Westhof, E. Aminoglycoside–RNA interactions. Curr. Opin. Chem. Biol. 3, 694–704 (1999).

Article  CAS  PubMed