294
12.2.1.2 Antibiotics
Antibiotics are low-molecular-weight metabolites produced by microorganisms that
at low concentrations interfere with the growth of other microorganisms. Antibiotics
generally fall within the size limit of about a few thousand Daltons at the maximum.
Microbial products of higher molecular weight like lysozyme and other complex
proteins do inhibit the growth of other microorganisms but are not considered as
antibiotics. The concentration at which an antibiotic acts is an important part of the
definition. At high concentrations, even amino acids like glycine and products of
anaerobic fermentation like ethanol or butanol can have a detrimental effect on the
growth of microorganisms but are not considered antibiotics. Although by definition
all antibiotics are strictly natural products, now the term encompasses semisynthetic
and completely synthetic variants of natural products too. Antibiotics are chemically
heterogeneous in nature. Based on the chemical structures, several families of antibiotics are identified. β-Lactam antibiotics are the first group to be discovered and are
characterized by a four-member ring closed by an amide bond. They are subdivided
into classes like penicillins, cephalosporins, carbapenems and monobactams. The
aminoglycoside group of antibiotics contains an alicyclic six- member ring with
hydroxyl and amino substitutes called the aminocyclitol ring along with a few sugars
or aminosugars. The tetracyclines contain four linearly condensed rings and act by
inhibiting protein synthesis, while the anthracyclines having the same structure act at
the DNA level. Macrolides with antibacterial activity are characterized by a large
lactone ring, while those with antifungal activity contain a few conjugated double
bonds in the lactone ring. Rifamycin group of antibiotics is made of aromatic rings
spanned by an aliphatic chain closed by an amide bond.
12.2.2 Modes of Action
Antimicrobials especially antibiotics exert their inhibitory potential by many different mechanisms essentially targeting vital steps in the survival or reproduction of
the microorganisms (Fig. 12.1). These mechanisms include inhibition of bacterial or
fungal cell wall assembly, blocking the synthesis of proteins, inhibition of nucleic
acid replication and inhibition of metabolism and alteration of plasma membrane
permeability.
12.2.3 Resistance to Antimicrobials
The clinical use of antimicrobials for the treatment of infections has been in practice
since the 1940s. The wonder drug penicillin was introduced into clinical practice
around this time. It did not take much for microorganisms to evolve strategies to
combat antimicrobials. By the mid-1940s penicillin-resistant Staphylococcus
aureus was reported. These strains of S. aureus produced a plasmid-encoded enzyme
called penicillinase (β-lactamase) that cleaved the β-lactam ring of penicillin. In an
attempt to combat antimicrobial resistance, the structure of penicillin was modified
D. Francis
12.2.1.2 Antibiotics
Antibiotics are low-molecular-weight metabolites produced by microorganisms that
at low concentrations interfere with the growth of other microorganisms. Antibiotics
generally fall within the size limit of about a few thousand Daltons at the maximum.
Microbial products of higher molecular weight like lysozyme and other complex
proteins do inhibit the growth of other microorganisms but are not considered as
antibiotics. The concentration at which an antibiotic acts is an important part of the
definition. At high concentrations, even amino acids like glycine and products of
anaerobic fermentation like ethanol or butanol can have a detrimental effect on the
growth of microorganisms but are not considered antibiotics. Although by definition
all antibiotics are strictly natural products, now the term encompasses semisynthetic
and completely synthetic variants of natural products too. Antibiotics are chemically
heterogeneous in nature. Based on the chemical structures, several families of antibiotics are identified. β-Lactam antibiotics are the first group to be discovered and are
characterized by a four-member ring closed by an amide bond. They are subdivided
into classes like penicillins, cephalosporins, carbapenems and monobactams. The
aminoglycoside group of antibiotics contains an alicyclic six- member ring with
hydroxyl and amino substitutes called the aminocyclitol ring along with a few sugars
or aminosugars. The tetracyclines contain four linearly condensed rings and act by
inhibiting protein synthesis, while the anthracyclines having the same structure act at
the DNA level. Macrolides with antibacterial activity are characterized by a large
lactone ring, while those with antifungal activity contain a few conjugated double
bonds in the lactone ring. Rifamycin group of antibiotics is made of aromatic rings
spanned by an aliphatic chain closed by an amide bond.
12.2.2 Modes of Action
Antimicrobials especially antibiotics exert their inhibitory potential by many different mechanisms essentially targeting vital steps in the survival or reproduction of
the microorganisms (Fig. 12.1). These mechanisms include inhibition of bacterial or
fungal cell wall assembly, blocking the synthesis of proteins, inhibition of nucleic
acid replication and inhibition of metabolism and alteration of plasma membrane
permeability.
12.2.3 Resistance to Antimicrobials
The clinical use of antimicrobials for the treatment of infections has been in practice
since the 1940s. The wonder drug penicillin was introduced into clinical practice
around this time. It did not take much for microorganisms to evolve strategies to
combat antimicrobials. By the mid-1940s penicillin-resistant Staphylococcus
aureus was reported. These strains of S. aureus produced a plasmid-encoded enzyme
called penicillinase (β-lactamase) that cleaved the β-lactam ring of penicillin. In an
attempt to combat antimicrobial resistance, the structure of penicillin was modified
D. Francis