This approach effectively restores the desired antimicrobial property (Brown 2015;
Fazly Bazzaz et al. 2018; Rana et al. 2018).
Antimicrobial agents exhibit their actions through various ways, including the
interfering with the biosynthesis or inhibiting bioactivities of bacterial components.
The established targets for antibiotics may include (a) biosynthesis of bacterial
proteins; (b) biosynthesis of bacterial cell wall; (c) damage of bacterial cell membrane; (d) interfering with bacterial DNA replication and/or repair mechanisms, and
(e) suppressing metabolic pathways. Some classes of antibiotic drugs like tetracyclines, macrolides, and aminoglycosides exhibit their antibacterial properties,
which particularly inhibit protein biosynthesis via targeting the ribosomal subunits
(Swamy et al. 2016; Khameneh et al. 2019). A protein is generally synthesized
inside the cells by several means of the molecular processes, including initiation,
elongation, termination, and assembly of protein-mediated by ribosomes. Hence,
bacterial pathogens can be targeted by inhibiting the actions of ribosomes and
affecting protein synthesis (Walsh 2003). Further, some antibiotics can modify the
permeability of the bacterial exterior cell membrane, and later disrupt the structural
alterations of cell membrane, leading to a rapid bacterial death by creating osmotic
imbalances. The polymyxin class of antibiotics attach to the lipid A constituent of
lipopolysaccharide, and results to cause cell membrane structural modifications
(McBain et al. 2003; Tenover 2006). Several classes of antibiotics inhibit cell wall
synthesis. Bacterial cell wall has covalently cross-linked strands of peptide and
glycan, and can be responsible for increased mechanical strength, and prevents cell
lysis due to osmotic pressure. The enzymes transglycosylases and transpeptidases
are responsible for forming this layer. Antibiotics such as penicillins and cephalosporins are shown to target the cell wall assembly, and exhibit bactericidal
properties. Antibiotics such as vancomycin is proved to, particularly disrupting the
peptidoglycan layer, and weaken the cell wall structure to result in bacterial cell
death (Schneider and Sahl 2010). The DNA gyrase enzyme is accounted to perform
the uncoiling and supercoiling of DNA strands, and controls DNA replication
process. Thus, targeting this enzyme can be another target for antibacterial drugs/
antibiotics. The antibiotics, ciprofloxacin (a fluoroquinolone), and nalidixic acid
suppress the replication of DNA by attaching to DNA Gyrase enzyme bound DNA
complex (Maxwell 1997). Bacteria might exhibit drug-resistance property to one or
more antibiotics via different types of mechanisms. The resistance property may
vary from one bacterial species to another and to different classes of antimicrobial
agents. So, knowing about the resistance mechanisms exhibited by bacterial strains
can be very useful in designing novel antibacterial drugs (Walsh 2003; Tenover
2006; Khameneh et al. 2016).
Noteworthy to mention here that the drug-resistance could be linked to a single
or more types of mode of actions together (Fig. 7.1). Some of the major proved
mechanisms of antibacterial drug-resistance by bacteria includes the destruction of
the antibiotic drugs by producing damaging enzymes, modifying antibiotic drugs by
secreting modifying enzymes, stimulation of efflux pumps, and changing the
structure of target in the bacterial cells, so that it will have less affinity for recognizing antibacterial agents (Khameneh et al. 2016; Munita and Arias 2016; Peterson
266
L. E. da Silva et al.
Fazly Bazzaz et al. 2018; Rana et al. 2018).
Antimicrobial agents exhibit their actions through various ways, including the
interfering with the biosynthesis or inhibiting bioactivities of bacterial components.
The established targets for antibiotics may include (a) biosynthesis of bacterial
proteins; (b) biosynthesis of bacterial cell wall; (c) damage of bacterial cell membrane; (d) interfering with bacterial DNA replication and/or repair mechanisms, and
(e) suppressing metabolic pathways. Some classes of antibiotic drugs like tetracyclines, macrolides, and aminoglycosides exhibit their antibacterial properties,
which particularly inhibit protein biosynthesis via targeting the ribosomal subunits
(Swamy et al. 2016; Khameneh et al. 2019). A protein is generally synthesized
inside the cells by several means of the molecular processes, including initiation,
elongation, termination, and assembly of protein-mediated by ribosomes. Hence,
bacterial pathogens can be targeted by inhibiting the actions of ribosomes and
affecting protein synthesis (Walsh 2003). Further, some antibiotics can modify the
permeability of the bacterial exterior cell membrane, and later disrupt the structural
alterations of cell membrane, leading to a rapid bacterial death by creating osmotic
imbalances. The polymyxin class of antibiotics attach to the lipid A constituent of
lipopolysaccharide, and results to cause cell membrane structural modifications
(McBain et al. 2003; Tenover 2006). Several classes of antibiotics inhibit cell wall
synthesis. Bacterial cell wall has covalently cross-linked strands of peptide and
glycan, and can be responsible for increased mechanical strength, and prevents cell
lysis due to osmotic pressure. The enzymes transglycosylases and transpeptidases
are responsible for forming this layer. Antibiotics such as penicillins and cephalosporins are shown to target the cell wall assembly, and exhibit bactericidal
properties. Antibiotics such as vancomycin is proved to, particularly disrupting the
peptidoglycan layer, and weaken the cell wall structure to result in bacterial cell
death (Schneider and Sahl 2010). The DNA gyrase enzyme is accounted to perform
the uncoiling and supercoiling of DNA strands, and controls DNA replication
process. Thus, targeting this enzyme can be another target for antibacterial drugs/
antibiotics. The antibiotics, ciprofloxacin (a fluoroquinolone), and nalidixic acid
suppress the replication of DNA by attaching to DNA Gyrase enzyme bound DNA
complex (Maxwell 1997). Bacteria might exhibit drug-resistance property to one or
more antibiotics via different types of mechanisms. The resistance property may
vary from one bacterial species to another and to different classes of antimicrobial
agents. So, knowing about the resistance mechanisms exhibited by bacterial strains
can be very useful in designing novel antibacterial drugs (Walsh 2003; Tenover
2006; Khameneh et al. 2016).
Noteworthy to mention here that the drug-resistance could be linked to a single
or more types of mode of actions together (Fig. 7.1). Some of the major proved
mechanisms of antibacterial drug-resistance by bacteria includes the destruction of
the antibiotic drugs by producing damaging enzymes, modifying antibiotic drugs by
secreting modifying enzymes, stimulation of efflux pumps, and changing the
structure of target in the bacterial cells, so that it will have less affinity for recognizing antibacterial agents (Khameneh et al. 2016; Munita and Arias 2016; Peterson
266
L. E. da Silva et al.