Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?

Abstract

Background Selective toxicity antibacteribiotics is considered to be due to interactions with targets either being unique to bacteria or being characterized by a dichotomy between pro- and eukaryotic pathways with high affinities of agents to bacterial- rather than eukaryotic targets. However, the theory of selective toxicity oversimplifies the complex modes of action of antibiotics in pro- and eukaryotes. Methods and objective This review summarizes data describing multiple modes of action of antibiotics in eukaryotes. Results Aminoglycosides, macrolides, oxazolidinones, chloramphenicol, clindamycin, tetracyclines, glycylcyclines, fluoroquinolones, rifampicin, bedaquillin, ß-lactams inhibited mitochondrial translation either due to binding to mitosomes, inhibition of mitochondrial RNA-polymerase-, topoisomerase 2ß-, ATP-synthesis, transporter activities. Oxazolidinones, tetracyclines, vancomycin, ß-lactams, bacitracin, isoniazid, nitroxoline inhibited matrix-metalloproteinases (MMP) due to chelation with zinc and calcium, whereas fluoroquinols fluoroquinolones and chloramphenicol chelated with these cations, too, but increased MMP activities. MMP-inhibition supported clinical efficacies of ß-lactams and daptomycin in skin-infections, and of macrolides, tetracyclines in respiratory-diseases. Chelation may have contributed to neuroprotection by ß-lactams and fluoroquinolones. Aminoglycosides, macrolides, chloramphenicol, oxazolidins oxazolidinones, tetracyclines caused read-through of premature stop codons. Several additional targets for antibiotics in human cells have been identified like interaction of fluoroquinolones with DNA damage repair in eukaryotes, or inhibition of mucin overproduction by oxazolidinones. Conclusion The effects of antibiotics on eukaryotes are due to identical mechanisms as their antibacterial activities because of structural and functional homologies of pro- and eukaryotic targets, so that the effects of antibiotics on mammals are integral parts of their overall mechanisms of action.

Correlation between Drug Resistance of Klebsiella Pneumonia and Antimicrobial Drug Usage

“…Antibacterial agents refer to products obtained from microorganisms such as bacteria, actinomycetes, and fungi in culture and also include various antibiotics, sulfonamides, imidazoles, nitroimidazoles, quinolones, and other chemically synthesized drugs [ 7 ]. Antimicrobial drugs have inhibitory and killing effects on pathogens at certain concentrations and are widely used in clinical practice [ 8 ]. Related studies have shown that the relationship between the use of antimicrobial drugs and bacterial resistance may provide guidance for the use of antimicrobial drugs [ 9 , 10 ].…”

The Very First Modification of Pleuromutilin and Lefamulin by Photoinitiated Radical Addition Reactions—Synthesis and Antibacterial Studies

“…The 2hydroxyethyl (14j) derivative was found to show potent antimicrobial activity against VanA resistant Enterococcus faecium strains isolated from urine, blood culture, drain and wound. Although the 50S ribosomal subunit occurs only in prokaryotes, antibiotics that inhibit protein synthesis by binding to the 50S subunit-as pleuromutilin derivates do-may be severely toxic to eukaryotes [36]. Therefore, it is essential to perform in vitro and in vivo toxicological studies of the active derivatives in the future.…”

The New Face of a Well-Known Antibiotic: A Review of the Anticancer Activity of Enoxacin and Its Derivatives

“…ENX is a 1,8-naphthyridine derivative of 1,4-dihydro-1,8naphthyridine with an ethyl group at the 1 position, a carboxy group at the 3-position, an oxo-substituent at the 4-position, a fluorine-substituent at the 5-position and a piperazin-1-yl group at the 7 position. Enoxacin inhibits bacterial DNA gyrase and topoisomerase IV [7,8]. Reports concerning its ability to interfere with human topoisomerase are contrary [1,[8][9][10] and it seems that this interaction is concentration-dependent [8].…”

“…Enoxacin inhibits bacterial DNA gyrase and topoisomerase IV [7,8]. Reports concerning its ability to interfere with human topoisomerase are contrary [1,[8][9][10] and it seems that this interaction is concentration-dependent [8].…”