Table 1.

Antibacterial agents, their mode of action and mechanisms of resistance [15,18,20,21,36,37,38,39,40,41,42].

Drug Class	Representatives (Drug Groups or Drugs)	Mechanism of Action	Drug Target	Mechanisms of AMR
Mechanism of action
Inhibition of cell wall synthesis
β lactams	Penicillins Cephalosporins Carbapenems Monobactams	Inhibition of cell wall synthesis	Peptidoglycan biosynthesis	Drug uptake limitation (decreased number of pores or changed selectivity of porins, no outer cell membrane) Enzymatic drug inactivation by hydrolysis (β lactamase production) RND 1 efflux pumps (reduction of drug absorption in the cell) Altered targets (PBP 2 alteration in gram-positive bacteria)
Glycopeptides	Vancomycin Teicoplanin		Peptidoglycan biosynthesis	Drug uptake limitation (thickened cell wall due to mutation, no outer cell wall or impermeable outer membrane in gram-negative bacteria) Altered targets (reprogramming of peptidoglycan biosynthesis via mutation of D-Ala-D-Ala ligase and peptidoglycan modification)
Disruption of bacterial cell inner membrane
Lipopeptides	Daptomycin	Disruption of bacterial cell inner membrane	Inner membrane	Enzymatic drug inactivation by immobilization a hydrolytic cleavage of the ester bond between the threonine and kynurenine residue Altered targets (genetically determined alteration of the cell surface charge leading to the repulsion of the anionic daptomycin molecules, changes in the membrane composition via the alteration of phospholipid membrane metabolism, alteration of complex transcriptional regulatory networks governing the cell envelope stress response and membrane homeostasis, indirectly affected cell wall synthesis and consequently—thickness
Disruption of cell membranes’ structure, primarily the outer membrane, that finally causes cell lysis
Cationic peptides	Colistin Polymyxin E	Disruption of cell membranes’ structure, primarily the outer membrane, that finally causes cell lysis 1	Cell membranes	Altered targets (overproduction of capsular polysaccharide, loss of LPSs 3 from bacterial outer membrane, modification of lipid A-pEtN 4 SMR 5 efflux pumps (reduction of drug absorption in the cell)
Aminoglycosides	Streptomycin Gentamicin Kanamycin Amikacin Tobramycin Spectinomycin	Inhibition of cytoplasm protein synthesis	Translation	Drug uptake limitation (cell wall polarity) Enzymatic drug inactivation (phosphorylation, acetylation, nucleotydilation) RND efflux pumps (reduction of drug absorption in the cell) Altered targets (ribosomal alteration due to mutation in 16S rRNA gene, methylation by the 16S ribosomal methylases)
Tetracyclines	Tetracycline Doxycycline Minocycline Tigecycline		Translation	Drug uptake limitation (decreased number of pores) Enzymatic drug inactivation (hydroxylation under FAD 6-dependent monooxygenases TetX 7 and TetX2 8) Efflux pumps (reduction of drug absorption in the cell) Altered targets (ribosomal protection)
Macrolides	Erythromycin Azithromycin Clarithromycin		Translation	Enzymatic drug inactivation (hydrolysis, glycosylation, phosphorylation) ABC 9, MFS 10, RND efflux pumps (reduction of drug absorption in the cell) Altered targets (ribosomal mutation, 23S rRNA methylation, ribosomal protection by ABC 11 proteins)
Lincosamides	Clindamycin		Translation	Altered targets (ribosomal methylation due to modification of 23S rRNA by methyltransferases in gram-positive bacteria) ABC, RND efflux pumps (reduction of drug absorption in the cell) Enzymatic drug inactivation (phosphorylation, nucleotidylation)
Amphenicols	Chloramphenicol		Translation	Enzymatic drug inactivation (acetylation) MFS, RND efflux pumps (reduction of drug absorption in the cell) Altered targets (ribosomal methylation due to mutations within 23S rRNA of the 50S ribosomal subunit)
Streptogramins	Quinupristin and dalfopristin		Translation	Altered target (ribosomal alteration due to mutation of 23S rRNA in 50S ribosomal subunit) ABC efflux pumps (reduction of drug absorption in the cell) Enzymatic dug inactivation (acetylation, breakage of a carbo-oxygen bond by carbon-oxygen lyase)
Oxazolidinones	Linezolid		Translation	Altered target (ribosomal methylation by methyltransferases via modification of the 23S rRNA, ribosomal protection by ABC proteins) RND efflux pumps (reduction of drug absorption in the cell)
Fluoroquinolones	Ciprofloxacin Ofloxacin Levofloxacin	Inhibition of nucleic acid synthesis	DNA replication	Enzymatic drug inactivation (acetylation) MATE 12, MFS, RND efflux pumps (reduction of drug absorption in the cell) Altered targets (DNA gyrase modification in gram-negative bacteria, topoisomerase IV modification—in gram-positive, protection of DNA gyrase and topoisomerase IV)
Rifamycins	Rifampin		RNA synthesis	Altered targets (mutation of rpoB gene which encodes the β subunit of RNA polymerase) RND, SMR efflux pumps (reduction of drug absorption in the cell)
Pyrimidines	Trimethoprim	Inhibition of metabolic pathways (folic acid metabolism)	DHFR 13	RND efflux pumps (reduction of drug absorption in the cell) Altered targets (reduced binding and overproduction of DHFR due to modification or acquisition of novel DHFR genes)
Sulfonamides	Sulfamethoxazole		DHPS 14	RND efflux pumps (reduction of drug absorption in the cell) Altered targets (DHPS reduce d binding, overproduction of resistant DHPS due to mutations in the DHPS gene and sul1/2 genes, which encode distinct DHPSs that are less susceptible to sulphonamide

¹ RND—Resistance Nodulation and Cell Division Superfamily, ² PBP—Penicillin binding proteins, ³ LPSs—lipopolysaccharides, ⁴ lipid A-pEtN—Lipid A phosphoethanolamine transferase, ⁵ SMR—Small Multidrug Resistance Superfamily, ⁶ FAD—Flavin adenine dinucleotide, ⁷ TetX—Monooxygenase conferring resistance to tetracycline antibiotics, ⁸ TetX2—Monooxygenase conferring resistance to tetracycline and tigecycline, ⁹ ABC—Adenosine triphosphate-binding cassette Superfamily of transmembrane transporters, ¹⁰ MFS—Major Facilitator Superfamily, ¹¹ ABC proteins—Members of adenosine triphosphate-binding cassette F proteins, ¹² MATE—Multidrug and Toxic Compound Extrusion Superfamily, ¹³ DHFR—Dihydrofolate reductase, ¹⁴ DHPS—Dihydropteroate synthase.