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multi drug resistant bacteria due to the misuse of the current antibiotics led to the
present urgent need to develop new antibiotics. In fact, the first antibiotic was purified from microorganisms. For instance, in the laboratory of Selman Waksman
dozen antibiotics were isolated from soil microorganisms, including a very potent
antibiotic known as Streptomycin (Waksman 1973). For the discovery of
Streptomycin, Waksman was awarded the Nobel Prize in Physiology or Medicine
in 1952.
This approach of antimicrobial drug discovery is based on bioactive screening on
whole cell, known as classical pharmacology. Having been identified a chemical
with antibacterial properties its molecular target has tried to be figured out. Most of
the antibiotics were discovered applying this approach during the “golden era”
(Waksman and Flynn 1973). This approach is also applicable to the present days.
Another method for antibacterial drug discovery is based on the high throughput
screening of chemical libraries for binding to a specific molecular target. An additional approach to antibacterial drug development is based on the rational design of
molecules that specifically bind to a predefined molecular target.
There are several recent trends to develop unconventional approaches to antibacterial drug discovery, which should be much more efficient than the currently
applied approaches. They include the genome wide search for novel antibacterial
targets and applying novel mechanisms of antibacterial drug action such as antisense oligonucleotides, phage based antibacterial and others.
9.5 Approaches for Antibiotic Discovery Including
Unconventional and Genomic Approaches
With the advancements of next generation sequencing technology, the genomes of
many strains of pathogenic bacteria are now well known. We can apply various
bioinformatics and experimental methods promising targets for antibacterial drug
discovery (Kaloudas et al. 2018). Moreover, applying metagenomics approaches,
we can investigate various horizontal transfers of genetic information among pathogenic bacteria and their interactions with other bacteria in the human body, for
instance, the gut microbiome. This gives us the opportunity to apply probiotic bacteria that can inhibit the proliferation of pathogenic bacteria, also using fecal microbiota transplantation methods.
Due to the advancements of structural biology and structural genomics, we can
use the 3D structures of key cellular organelles to develop drug candidates using
various computational methods. For instance, after solving the 3D structure of the
bacterial ribosome, many researchers are trying to rationally design antibiotics that
inhibit the function of the bacterial ribosome but are harmless to the human ribosome (Shasmal and Sengupta 2012). As a result of the discovery of regulation of
gene expression by bacterial riboswitches (Pavlova and Penchovsky 2019), a whole
class of new antibacterial drug targets are discovered that can be targeted not only
9 Drug Discovery for Targeting Drug Resistant Bacteria
multi drug resistant bacteria due to the misuse of the current antibiotics led to the
present urgent need to develop new antibiotics. In fact, the first antibiotic was purified from microorganisms. For instance, in the laboratory of Selman Waksman
dozen antibiotics were isolated from soil microorganisms, including a very potent
antibiotic known as Streptomycin (Waksman 1973). For the discovery of
Streptomycin, Waksman was awarded the Nobel Prize in Physiology or Medicine
in 1952.
This approach of antimicrobial drug discovery is based on bioactive screening on
whole cell, known as classical pharmacology. Having been identified a chemical
with antibacterial properties its molecular target has tried to be figured out. Most of
the antibiotics were discovered applying this approach during the “golden era”
(Waksman and Flynn 1973). This approach is also applicable to the present days.
Another method for antibacterial drug discovery is based on the high throughput
screening of chemical libraries for binding to a specific molecular target. An additional approach to antibacterial drug development is based on the rational design of
molecules that specifically bind to a predefined molecular target.
There are several recent trends to develop unconventional approaches to antibacterial drug discovery, which should be much more efficient than the currently
applied approaches. They include the genome wide search for novel antibacterial
targets and applying novel mechanisms of antibacterial drug action such as antisense oligonucleotides, phage based antibacterial and others.
9.5 Approaches for Antibiotic Discovery Including
Unconventional and Genomic Approaches
With the advancements of next generation sequencing technology, the genomes of
many strains of pathogenic bacteria are now well known. We can apply various
bioinformatics and experimental methods promising targets for antibacterial drug
discovery (Kaloudas et al. 2018). Moreover, applying metagenomics approaches,
we can investigate various horizontal transfers of genetic information among pathogenic bacteria and their interactions with other bacteria in the human body, for
instance, the gut microbiome. This gives us the opportunity to apply probiotic bacteria that can inhibit the proliferation of pathogenic bacteria, also using fecal microbiota transplantation methods.
Due to the advancements of structural biology and structural genomics, we can
use the 3D structures of key cellular organelles to develop drug candidates using
various computational methods. For instance, after solving the 3D structure of the
bacterial ribosome, many researchers are trying to rationally design antibiotics that
inhibit the function of the bacterial ribosome but are harmless to the human ribosome (Shasmal and Sengupta 2012). As a result of the discovery of regulation of
gene expression by bacterial riboswitches (Pavlova and Penchovsky 2019), a whole
class of new antibacterial drug targets are discovered that can be targeted not only
9 Drug Discovery for Targeting Drug Resistant Bacteria