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rendering it resistant to five antimicrobials, namely, ampicillin, chloramphenicol,
streptomycin, sulfonamides and tetracycline, has been reported. Shigella, the causative agent of shigellosis, has developed resistance against cotrimoxazole. Neisseria
gonorrhoeae, responsible for gonorrhea, has been reported to evolve reduced susceptibilities to third-generation cephalosporins and such strains were found to be
resistant to almost all antibiotics relevant for treatment. They are classified as multidrug-resistant gonococci. Microorganisms develop resistance to antimicrobials by
four general mechanisms: inactivation or modification of the antibiotic, structural
modification of the antibiotic target so as to reduce the binding affinity of the antibiotic, modification of the metabolic pathways to prevent the action of antibiotics and
reduction in intracellular accumulation of antimicrobials by decreasing the permeability of membranes or enabling efflux mechanisms to prevent entry of antibiotics.
12.3 Antimicrobial Secondary Metabolites
Secondary metabolites represent the microbial metabolites found as specially differentiated molecules restricted to specific taxonomic groups and are not essential
for cellular metabolism. The term was introduced by Bu’Lock in the early 1960s to
differentiate such molecules from the primary essential metabolites including sugars, amino acids and nucleic acids produced by all organisms. Secondary metabolites are generally low-molecular-weight microbial products synthesized by specific
microbes as part of the biochemical differentiation of the producer. They do not
have any specific role in the growth or survival of the producer in cultures, and
mutant strains that do not produce a specific metabolite remain unaffected in terms
of cellular growth and metabolism. They are most often produced as families of
similar structure and activity. Polyketides, terpenes, shikimates, peptides and alkaloids represent various classes of secondary metabolites produced by microorganism classified based on biosynthetic origin. In microorganisms grown in cultures,
secondary metabolite production is at the lowest during lag and logarithmic phases
of growth and is at the maximum during the stationary phase. Most of the pharmaceutically important bioactive molecules produced by microorganisms are secondary metabolites. The ability to produce bioactive secondary metabolites is highly
varied among microorganisms (Fig. 12.2). Among unicellular prokaryotic bacteria
order Actinomycetales, genus Bacillus and genus Pseudomonas represent the most
prolific producers of bioactive metabolites. Recently Myxobacteria and
Cyanobacteria joined the group with large number of bioactive compounds being
reported. Mycobacteria and Mycoplasmatales represent a relatively dull group of
producers with a share of only around 3800 metabolites (17%). The filamentous
Actinomycetales are the largest group of producers with more than 10,000 (around
45% of all microbial secondary metabolites) bioactive metabolites identified. About
7600 of them are produced by the genus Streptomyces and around 2500 are produced by rare actinomycetes. Among the microscopic fungi ascomycetes, basidiomycetes and other filamentous endophytic fungi are the most significant producers.
Yeasts, phycomycetes and slime molds are weak producers of bioactive secondary
D. Francis
rendering it resistant to five antimicrobials, namely, ampicillin, chloramphenicol,
streptomycin, sulfonamides and tetracycline, has been reported. Shigella, the causative agent of shigellosis, has developed resistance against cotrimoxazole. Neisseria
gonorrhoeae, responsible for gonorrhea, has been reported to evolve reduced susceptibilities to third-generation cephalosporins and such strains were found to be
resistant to almost all antibiotics relevant for treatment. They are classified as multidrug-resistant gonococci. Microorganisms develop resistance to antimicrobials by
four general mechanisms: inactivation or modification of the antibiotic, structural
modification of the antibiotic target so as to reduce the binding affinity of the antibiotic, modification of the metabolic pathways to prevent the action of antibiotics and
reduction in intracellular accumulation of antimicrobials by decreasing the permeability of membranes or enabling efflux mechanisms to prevent entry of antibiotics.
12.3 Antimicrobial Secondary Metabolites
Secondary metabolites represent the microbial metabolites found as specially differentiated molecules restricted to specific taxonomic groups and are not essential
for cellular metabolism. The term was introduced by Bu’Lock in the early 1960s to
differentiate such molecules from the primary essential metabolites including sugars, amino acids and nucleic acids produced by all organisms. Secondary metabolites are generally low-molecular-weight microbial products synthesized by specific
microbes as part of the biochemical differentiation of the producer. They do not
have any specific role in the growth or survival of the producer in cultures, and
mutant strains that do not produce a specific metabolite remain unaffected in terms
of cellular growth and metabolism. They are most often produced as families of
similar structure and activity. Polyketides, terpenes, shikimates, peptides and alkaloids represent various classes of secondary metabolites produced by microorganism classified based on biosynthetic origin. In microorganisms grown in cultures,
secondary metabolite production is at the lowest during lag and logarithmic phases
of growth and is at the maximum during the stationary phase. Most of the pharmaceutically important bioactive molecules produced by microorganisms are secondary metabolites. The ability to produce bioactive secondary metabolites is highly
varied among microorganisms (Fig. 12.2). Among unicellular prokaryotic bacteria
order Actinomycetales, genus Bacillus and genus Pseudomonas represent the most
prolific producers of bioactive metabolites. Recently Myxobacteria and
Cyanobacteria joined the group with large number of bioactive compounds being
reported. Mycobacteria and Mycoplasmatales represent a relatively dull group of
producers with a share of only around 3800 metabolites (17%). The filamentous
Actinomycetales are the largest group of producers with more than 10,000 (around
45% of all microbial secondary metabolites) bioactive metabolites identified. About
7600 of them are produced by the genus Streptomyces and around 2500 are produced by rare actinomycetes. Among the microscopic fungi ascomycetes, basidiomycetes and other filamentous endophytic fungi are the most significant producers.
Yeasts, phycomycetes and slime molds are weak producers of bioactive secondary
D. Francis