341
crystallographic techniques that play crucial roles along with genomics, molecular
biology, and proteomics in the discovery and clinical availability of novel antimicrobial compounds. Reduction in turnaround times and improvements in data quality can be achieved by advancements in automation and employment of
computer- assisted data analysis.
Metagenomics is a culture-independent approach used largely to identify
microbes and get detailed information about the diversity of them from environmental samples. In metagenomics the results are obtained by DNA sequence analysis (de Castro et al. 2014). Next-generation deep sequencing and data analysis
methods raise metagenomics to a new plain by providing accurate and detailed
sequence information for understanding the compounds produced by microbes and
mechanisms of antibiotic resistance in the in situ microbial community (Forsberg
et al. 2012; McGarvey et al. 2012).
Genome sequencing of various microorganisms resulted in identification of gene
clusters that are believed to direct the production of unknown metabolites. Prediction
of role of a gene or a gene cluster in production of previously unknown natural
compounds is made possible by a novel technique called microbial genome mining
(Davies 2011). Identification of a novel peptide, coelichelin, from Streptomyces
coelicolor can be cited as an example of fruitful culmination of genome mining
(Challis and Ravel 2000). Possibility of the presence of numerous bioactive compounds that are yet to be identified and characterized is evident from such
findings.
Imaging mass spectrometry is an immensely useful technique in the field of natural product research (Esquenazi et al. 2009). IMS enables researchers to visualize
the spatial distribution of chemical compositions, e.g., compounds, metabolites, and
peptides on a substrate such as a plant part. This method helps researchers to identify symbiotic microorganisms as the true producers of secondary metabolites
(Esquenazi et al. 2009; Simmons et al. 2008a). A slight modification of IMS, called
thin layer agar natural product matrix-assisted laser desorption/ionization-time of
fligh (MALDI-TOF) imaging, brought in possibility of analyzing a complete set of
metabolites produced by microorganisms under various culturing conditions. These
microorganisms are cultured on thin agar film on a MALDI plate followed by application of matrix and analysis by MALDI (Yang et al. 2009).
Isolation chip (iChip) is a novel high-throughput platform for parallel cultivation
and isolation of previously uncultivable microbial species in situ within their natural
environments. Teixobactin is the new compound identified by employing this
method (Wright 2015). The bacterium that produces teixobactin is a hitherto undescribed microorganism, which was provisionally named as Eleftheria terrae
(Piddock 2015). Teixobactin was able to cure mice of various bacterial infections
including pneumonia and blood infections but is yet to undergo human trials. This
compound inhibits cell wall synthesis of bacteria in a unique way – by inhibiting
peptidoglycan biosynthesis by binding to a highly conserved motif of precursors of
peptidoglycan (lipid II) and teichoic acid (lipid III) – that is likely to avoid development of drug resistance (ling et al. 2015). The scientific world is optimistic about
discovery of new potential antibiotics with the help of iChip technology.
13 Novel Sources of Antimicrobials
crystallographic techniques that play crucial roles along with genomics, molecular
biology, and proteomics in the discovery and clinical availability of novel antimicrobial compounds. Reduction in turnaround times and improvements in data quality can be achieved by advancements in automation and employment of
computer- assisted data analysis.
Metagenomics is a culture-independent approach used largely to identify
microbes and get detailed information about the diversity of them from environmental samples. In metagenomics the results are obtained by DNA sequence analysis (de Castro et al. 2014). Next-generation deep sequencing and data analysis
methods raise metagenomics to a new plain by providing accurate and detailed
sequence information for understanding the compounds produced by microbes and
mechanisms of antibiotic resistance in the in situ microbial community (Forsberg
et al. 2012; McGarvey et al. 2012).
Genome sequencing of various microorganisms resulted in identification of gene
clusters that are believed to direct the production of unknown metabolites. Prediction
of role of a gene or a gene cluster in production of previously unknown natural
compounds is made possible by a novel technique called microbial genome mining
(Davies 2011). Identification of a novel peptide, coelichelin, from Streptomyces
coelicolor can be cited as an example of fruitful culmination of genome mining
(Challis and Ravel 2000). Possibility of the presence of numerous bioactive compounds that are yet to be identified and characterized is evident from such
findings.
Imaging mass spectrometry is an immensely useful technique in the field of natural product research (Esquenazi et al. 2009). IMS enables researchers to visualize
the spatial distribution of chemical compositions, e.g., compounds, metabolites, and
peptides on a substrate such as a plant part. This method helps researchers to identify symbiotic microorganisms as the true producers of secondary metabolites
(Esquenazi et al. 2009; Simmons et al. 2008a). A slight modification of IMS, called
thin layer agar natural product matrix-assisted laser desorption/ionization-time of
fligh (MALDI-TOF) imaging, brought in possibility of analyzing a complete set of
metabolites produced by microorganisms under various culturing conditions. These
microorganisms are cultured on thin agar film on a MALDI plate followed by application of matrix and analysis by MALDI (Yang et al. 2009).
Isolation chip (iChip) is a novel high-throughput platform for parallel cultivation
and isolation of previously uncultivable microbial species in situ within their natural
environments. Teixobactin is the new compound identified by employing this
method (Wright 2015). The bacterium that produces teixobactin is a hitherto undescribed microorganism, which was provisionally named as Eleftheria terrae
(Piddock 2015). Teixobactin was able to cure mice of various bacterial infections
including pneumonia and blood infections but is yet to undergo human trials. This
compound inhibits cell wall synthesis of bacteria in a unique way – by inhibiting
peptidoglycan biosynthesis by binding to a highly conserved motif of precursors of
peptidoglycan (lipid II) and teichoic acid (lipid III) – that is likely to avoid development of drug resistance (ling et al. 2015). The scientific world is optimistic about
discovery of new potential antibiotics with the help of iChip technology.
13 Novel Sources of Antimicrobials