Domain dissection and characterization of the aminoglycoside resistance enzyme ANT(3″)-Ii/AAC(6′)-IId from Serratia marcescens

Green, Keith D.

doi:10.1016/j.biochi.2013.02.011

Cited by 12 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We decided to evaluate the ability of AMEs to modify our synthesized KANB derivatives 3a – e and 4c , d by measuring the relative activities of six enzymes with these KANB derivatives and comparing them to that of the parent AG, KANB (Figure 1). Among the six AMEs were APH(2″)-Ia, 34 AAC(3)-IV, 35 AAC(6′)-Ie/APH(2″)-Ia (used for its AAC(6′)-Ie activity only), 35 AAC(6′)-IId, 36 AAC(2′)-Ic, 37 and the multiacetylating enzyme Eis, 37,38 with the latter two both being specific to Mycobacterium tuberculosis . Overall, there was a noticeable decrease in activity of these AMEs with all seven derivatives 3a – e and 4c , d .…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Bioactivities of Kanamycin B-Derived Cationic Amphiphiles

et al. 2015

Self Cite

View full text Add to dashboard Cite

Cationic amphiphiles derived from aminoglycosides (AGs) have been shown to exhibit enhanced antimicrobial activity. Through the attachment of hydrophobic residues such as linear alkyl chains on the AG backbone, interesting antibacterial and antifungal agents with a novel mechanism of action have been developed. Herein, we report the design and synthesis of seven kanamycin B (KANB) derivatives. Their antibacterial and antifungal activities, along with resistance/enzymatic, hemolytic, and cytotoxicity assays were also studied. Two of these compounds, with a C12 and C14 aliphatic chain attached at the 6″-position of KANB through a thioether linkage, exhibited good antibacterial and antifungal activity, were poorer substrates than KANB for several AG-modifying enzymes, and could delay the development of resistance in bacteria and fungi. Also, they were both relatively less hemolytic than the known membrane targeting antibiotic gramicidin and the known antifungal agent amphotericin B and were not toxic at their antifungal MIC values. Their oxidation to sulfones was also demonstrated to have no effect on their activities. Moreover, they both acted synergistically with posaconazole, an azole currently used in the treatment of human fungal infections.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis and Bioactivities of Kanamycin B-Derived Cationic Amphiphiles

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…5A). Also, bifunctional enzymes, such as AAC(6′)-Ie/APH(2″)-Ia from Staphylococcus aureus , 109–112 AAC(3)-Ib/AAC(6′)-Ib′ from P. aeruginosa , 113, 114 ANT(3″)-Ii/AAC(6′)-IId from Serratia marcescens , 115–117 and AAC(6′)-30/AAC(6′)-Ib from P. aeruginosa 118, 119 exist and are capable of multiple types of AG modification. AAC(6′)-Ib is the most prevalent and clinically relevant AME; approximately fifty variants of AAC(6′)-Ib exist in numerous Gram-negative species.…”

Section: Ag-modifying Enzymesmentioning

confidence: 99%

Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives

2016

Self Cite

View full text Add to dashboard Cite

Aminoglycoside (AG) antibiotics are used to treat many Gram-negative and some Gram-positive infections and, importantly, multidrug-resistant tuberculosis. Among various bacterial species, resistance to AGs arises through a variety of intrinsic and acquired mechanisms. The bacterial cell wall serves as a natural barrier for small molecules such as AGs and may be further fortified via acquired mutations. Efflux pumps work to expel AGs from bacterial cells, and modifications here too may cause further resistance to AGs. Mutations in the ribosomal target of AGs, while rare, also contribute to resistance. Of growing clinical prominence is resistance caused by ribosome methyltransferases. By far the most widespread mechanism of resistance to AGs is the inactivation of these antibiotics by AG-modifying enzymes. We provide here an overview of these mechanisms by which bacteria become resistant to AGs and discuss their prevalence and potential for clinical relevance.

show abstract

“…The bifunctional ANT(3’’)-Ii/AAC(6’)-IId enzyme is characterized by a combination of nucleotidyltransferase activity against streptomycin and spectinomycin and acetyltransferase activity with broad substrate specificity [91].…”

Section: Bifunctional Enzymes: a New Evolutionary Trendmentioning

confidence: 99%

Bacterial Enzymes and Antibiotic Resistance

2018

View full text Add to dashboard Cite

The resistance of microorganisms to antibiotics has been developing for more than 2 billion years and is widely distributed among various representatives of the microbiological world. Bacterial enzymes play a key role in the emergence of resistance. Classification of these enzymes is based on their participation in various biochemical mechanisms: modification of the enzymes that act as antibiotic targets, enzymatic modification of intracellular targets, enzymatic transformation of antibiotics, and the implementation of cellular metabolism reactions. The main mechanisms of resistance development are associated with the evolution of superfamilies of bacterial enzymes due to the variability of the genes encoding them. The collection of all antibiotic resistance genes is known as the resistome. Tens of thousands of enzymes and their mutants that implement various mechanisms of resistance form a new community that is called the enzystome. Analysis of the structure and functional characteristics of enzymes, which are the targets for different classes of antibiotics, will allow us to develop new strategies for overcoming the resistance.

show abstract

Domain dissection and characterization of the aminoglycoside resistance enzyme ANT(3″)-Ii/AAC(6′)-IId from Serratia marcescens

Cited by 12 publications

References 28 publications

Synthesis and Bioactivities of Kanamycin B-Derived Cationic Amphiphiles

Synthesis and Bioactivities of Kanamycin B-Derived Cationic Amphiphiles

Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives

Bacterial Enzymes and Antibiotic Resistance

Contact Info

Product

Resources

About