scholarly journals Looking Back to Amycolatopsis: History of the Antibiotic Discovery and Future Prospects

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1254
Author(s):  
Olga V. Kisil ◽  
Tatiana A. Efimenko ◽  
Olga V. Efremenkova
Keyword(s):  
Pathogenic Bacteria ◽  
Antibacterial Agents ◽  
Gene Clusters ◽  
Future Prospects ◽  
Genome Sequences ◽  
Biosynthetic Gene Clusters ◽  
Antibiotic Resistant ◽  
New Antibiotics ◽  
History Of ◽  
Antibiotic Discovery

The emergence of antibiotic-resistant pathogenic bacteria in recent decades leads us to an urgent need for the development of new antibacterial agents. The species of the genus Amycolatopsis are known as producers of secondary metabolites that are used in medicine and agriculture. The complete genome sequences of the Amycolatopsis demonstrate a wide variety of biosynthetic gene clusters, which highlights the potential ability of actinomycetes of this genus to produce new antibiotics. In this review, we summarize information about antibiotics produced by Amycolatopsis species. This knowledge demonstrates the prospects for further study of this genus as an enormous source of antibiotics.

scholarly journals Draft Genome Sequences of the Three Massilia Strains AB1, ST3, and ZL223

2021 ◽  
Vol 10 (30) ◽  
Author(s):  
Ariel A. Bradley ◽  
Zoephia Laughlin ◽  
Saralexis Torres ◽  
Loralyn M. Cozy
Keyword(s):  
Draft Genome ◽  
Genomic Data ◽  
Gene Clusters ◽  
Nucleotide Identity ◽  
Average Nucleotide Identity ◽  
Biosynthetic Gene ◽  
Genome Sequences ◽  
Biosynthetic Gene Clusters ◽  
Antibiotic Discovery

To increase the genomic data available for antibiotic discovery, three independently isolated antibiotic-producing Massilia strains were sequenced. No more than 84% average nucleotide identity was shared with publicly available Massilia genomes, and a low similarity of predicted biosynthetic gene clusters to known clusters was found.

scholarly journals The Missing Link: Developing a pipeline for accelerated antibiotic discovery from Streptomyces through linking ‘omics data

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Darren Scobie ◽  
Grimur Hjorleifsson ◽  
Paul Herron ◽  
Simon Rogers ◽  
Katherine Duncan
Keyword(s):  
Genome Mining ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Genome Sequences ◽  
Biosynthetic Gene Clusters ◽  
Specialized Metabolites ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Comparative Metabolomics ◽  
Antibiotic Discovery

The genus Streptomyces has proven to be a rich reservoir of specialized metabolites, accounting for 80% of all microbially produced antibiotics including chloramphenicol and nystatin from S. venezuelae and S. noursei respectively. However, the discovery of novel microbial chemistry is still greatly needed to combat antimicrobial resistance. Comparative metabolomics, using platforms such as Global Natural Products Social Molecular Networking (GNPS), as well as tools such as antiSMASH and BiGSCAPE have aided the mining of biosynthetic gene clusters (BGC’s) across datasets but comparing the chemistry to the encoding biosynthetic gene clusters is a significant bottleneck. In this study, ten Streptomyces strains were selected, based on phylogeny and availability of genome sequence. The strains were cultured on 6 types of Actinomycete-specific media to maximise metabolite diversity. Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) was used to obtain spectral data from crude metabolite extracts enabling comparative metabolomics analysis via the GNPS platform. As the genome sequences were publicly available, genome mining of BGC’s was achieved using antiSMASH resulting in 260 BGC’s across the ten strains. This revealed 53 gene cluster families when analysed using BiGSCAPE, the largest encoding for 8 metabolites. In future, both biosynthetic (BGC’s) and chemistry (parent ions) datasets will be computationally linked based on strain presence/absence. The development of standardised datasets that enable cross-‘omics comparison will aid prioritisation of novel antibiotics, especially when combined with bioactivity data.

scholarly journals SYN-View: A Phylogeny-Based Synteny Exploration Tool for the Identification of Gene Clusters Linked to Antibiotic Resistance

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 144
Author(s):  
Jason Stahlecker ◽  
Erik Mingyar ◽  
Nadine Ziemert ◽  
Mehmet Direnç Mungan
Keyword(s):  
Natural Products ◽  
Pathogenic Bacteria ◽  
Target Genes ◽  
Genome Mining ◽  
Gene Clusters ◽  
Biosynthetic Gene Clusters ◽  
Antibiotic Resistant ◽  
The Arts ◽  
Exploration Tool

The development of new antibacterial drugs has become one of the most important tasks of the century in order to overcome the posing threat of drug resistance in pathogenic bacteria. Many antibiotics originate from natural products produced by various microorganisms. Over the last decades, bioinformatical approaches have facilitated the discovery and characterization of these small compounds using genome mining methodologies. A key part of this process is the identification of the most promising biosynthetic gene clusters (BGCs), which encode novel natural products. In 2017, the Antibiotic Resistant Target Seeker (ARTS) was developed in order to enable an automated target-directed genome mining approach. ARTS identifies possible resistant target genes within antibiotic gene clusters, in order to detect promising BGCs encoding antibiotics with novel modes of action. Although ARTS can predict promising targets based on multiple criteria, it provides little information about the cluster structures of possible resistant genes. Here, we present SYN-view. Based on a phylogenetic approach, SYN-view allows for easy comparison of gene clusters of interest and distinguishing genes with regular housekeeping functions from genes functioning as antibiotic resistant targets. Our aim is to implement our proposed method into the ARTS web-server, further improving the target-directed genome mining strategy of the ARTS pipeline.

Future directions for the discovery of antibiotics from actinomycete bacteria

2017 ◽  
Vol 1 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Rebecca Devine ◽  
Matthew I. Hutchings ◽  
Neil A. Holmes
Keyword(s):  
New Technologies ◽  
Gene Clusters ◽  
Biosynthetic Gene Clusters ◽  
Future Directions ◽  
Streptomyces Species ◽  
Genus Streptomyces ◽  
New Antibiotics ◽  
The Uk ◽  
Almost All ◽  
New Generation

Antimicrobial resistance (AMR) is a growing societal problem, and without new anti-infective drugs, the UK government-commissioned O'Neil report has predicted that infectious disease will claim the lives of an additional 10 million people a year worldwide by 2050. Almost all the antibiotics currently in clinical use are derived from the secondary metabolites of a group of filamentous soil bacteria called actinomycetes, most notably in the genus Streptomyces. Unfortunately, the discovery of these strains and their natural products (NPs) peaked in the 1950s and was then largely abandoned, partly due to the repeated rediscovery of known strains and compounds. Attention turned instead to rational target-based drug design, but this was largely unsuccessful and few new antibiotics have made it to clinic in the last 60 years. In the early 2000s, however, genome sequencing of the first Streptomyces species reinvigorated interest in NP discovery because it revealed the presence of numerous cryptic NP biosynthetic gene clusters that are not expressed in the laboratory. Here, we describe how the use of new technologies, including improved culture-dependent and -independent techniques, combined with searching underexplored environments, promises to identify a new generation of NP antibiotics from actinomycete bacteria.

scholarly journals Complete Genome Sequences of Five Burkholderia Strains with Biocontrol Activity against Various Lettuce Pathogens

2022 ◽  
Author(s):  
Adrien Biessy ◽  
Marie Ciotola ◽  
Mélanie Cadieux ◽  
Daphné Albert ◽  
Martin Filion
Keyword(s):  
Complete Genome ◽  
Burkholderia Cepacia ◽  
Gene Clusters ◽  
Antimicrobial Compounds ◽  
Bacterial Strains ◽  
Genome Sequences ◽  
Biosynthetic Gene Clusters ◽  
Content Type ◽  
Biocontrol Activity ◽  
Complex Display

Numerous bacterial strains from the Burkholderia cepacia complex display biocontrol activity. Here, we report the complete genome sequences of five Burkholderia strains isolated from soil. Biosynthetic gene clusters responsible for the production of antimicrobial compounds were found in the genome of these strains, which display biocontrol activity against various lettuce pathogens.

scholarly journals Thinking Outside the Bug: Molecular Targets and Strategies to Overcome Antibiotic Resistance

2019 ◽  
Vol 20 (6) ◽  
pp. 1255 ◽  
Author(s):  
Ana Monserrat-Martinez ◽  
Yann Gambin ◽  
Emma Sierecki
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Rational Design ◽  
Disease Onset ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
New Antibiotics ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Antibiotic Discovery

Since their discovery in the early 20th century, antibiotics have been used as the primary weapon against bacterial infections. Due to their prophylactic effect, they are also used as part of the cocktail of drugs given to treat complex diseases such as cancer or during surgery, in order to prevent infection. This has resulted in a decrease of mortality from infectious diseases and an increase in life expectancy in the last 100 years. However, as a consequence of administering antibiotics broadly to the population and sometimes misusing them, antibiotic-resistant bacteria have appeared. The emergence of resistant strains is a global health threat to humanity. Highly-resistant bacteria like Staphylococcus aureus (methicillin-resistant) or Enterococcus faecium (vancomycin-resistant) have led to complications in intensive care units, increasing medical costs and putting patient lives at risk. The appearance of these resistant strains together with the difficulty in finding new antimicrobials has alarmed the scientific community. Most of the strategies currently employed to develop new antibiotics point towards novel approaches for drug design based on prodrugs or rational design of new molecules. However, targeting crucial bacterial processes by these means will keep creating evolutionary pressure towards drug resistance. In this review, we discuss antibiotic resistance and new options for antibiotic discovery, focusing in particular on new alternatives aiming to disarm the bacteria or empower the host to avoid disease onset.

scholarly journals Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites

2020 ◽  
Vol 8 (12) ◽  
pp. 1897
Author(s):  
Shraddha Shitut ◽  
Güniz Özer Bergman ◽  
Alexander Kros ◽  
Daniel E. Rozen ◽  
Dennis Claessen
Keyword(s):  
Cell Wall ◽  
Secondary Metabolites ◽  
Gene Clusters ◽  
Chemical Diversity ◽  
Biosynthetic Gene Clusters ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Genome Recombination ◽  
Antibiotic Discovery ◽  
Insight Into

Filamentous actinobacteria are widely used as microbial cell factories to produce valuable secondary metabolites, including the vast majority of clinically relevant antimicrobial compounds. Secondary metabolites are typically encoded by large biosynthetic gene clusters, which allow for a modular approach to generating diverse compounds through recombination. Protoplast fusion is a popular method for whole genome recombination that uses fusion of cells that are transiently wall-deficient. This process has been applied for both inter- and intraspecies recombination. An important limiting step in obtaining diverse recombinants from fused protoplasts is regeneration of the cell wall, because this forces the chromosomes from different parental lines to segregate, thereby preventing further recombination. Recently, several labs have gained insight into wall-deficient bacteria that have the ability to proliferate without their cell wall, known as L-forms. Unlike protoplasts, L-forms can stably maintain multiple chromosomes over many division cycles. Fusion of such L-forms would potentially allow cells to express genes from both parental genomes while also extending the time for recombination, both of which can contribute to an increased chemical diversity. Here, we present a perspective on how L-form fusion has the potential to become a platform for novel compound discovery and may thus help to overcome the antibiotic discovery void.

scholarly journals Quorum Sensing: A Non-conventional Target for Antibiotic Discovery

2013 ◽  
Vol 8 (10) ◽  
pp. 1934578X1300801
Author(s):  
Varsha Naik ◽  
Girish Mahajan
Keyword(s):  
Quorum Sensing ◽  
Pathogenic Bacteria ◽  
Model Organism ◽  
Homoserine Lactone ◽  
Virulence Determinants ◽  
Antibiotic Resistant ◽  
Pigment Synthesis ◽  
Time Points ◽  
Antibiotic Discovery ◽  
Different Doses

Quorum sensing (QS) is known to regulate different functions viz. pathogenesis, biofilm formation, and host colonization, along with other functions by regulating bacterial virulence determinants. Therefore, QS is deemed to be an interesting target to modulate pathogenesis. Also, there have been global reports of continuous emergence of antibiotic-resistant microbes; hence, an alternative treatment that compliments antibiotic activity is highly desirable. One such approach is to look for QS inhibitors, which can quench the virulence phenotypes exerted by pathogenic bacteria and compliment antibiotic treatment. In the present study, Pseudomonas aeruginosa strain was used as the model organism which produces three pigments viz. pyocyanin, pyoverdin and pyorubin. Pyocyanin synthesis is reported to be QS dependent and is one of the virulence factors of P. aeruginosa. Hence, we envisage inhibition of pyocyanin pigment would indicate QS inhibition (QSI). Auto-inducers like N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL/3-oxo-C12-HSL) and N-butyryl-L- homoserine lactone (BHL/C4-HSL) were used to enhance the pyocyanin pigment production by the model strain at different doses and time points. BHL, at 25 μM was found to be a better inducer of pyocyanin. Tannic acid (TA) was tested to suppress this pigment synthesis and it was found to be effective when assessed at different time points. About 5.12 mg/mL TA was found to be the optimum concentration at which pyocyanin was inhibited by 77.3%. Thus, we confirm that TA can be used as a QSI, either in its purest form or in the crude form found in various plant species, and could be considered for development to compliment antibiotic therapy.

Something old, something new: revisiting natural products in antibiotic drug discovery

2014 ◽  
Vol 60 (3) ◽  
pp. 147-154 ◽  
Author(s):  
Gerard D. Wright
Keyword(s):  
Natural Products ◽  
New Drugs ◽  
Clinical Use ◽  
Antibiotic Resistant ◽  
Antibiotic Drug ◽  
New Antibiotics ◽  
Bacteria And Fungi ◽  
Antibiotic Discovery ◽  
Novel Drug ◽  
New Strategies

Antibiotic discovery is in crisis. Despite a growing need for new drugs resulting from the increasing number of multi-antibiotic-resistant pathogens, there have been only a handful of new antibiotics approved for clinical use in the past 2 decades. Faced with scientific, economic, and regulatory challenges, the pharmaceutical sector seems unable to respond to what has been called an “apocalyptic” threat. Natural products produced by bacteria and fungi are genetically encoded products of natural selection that have been the mainstay sources of the antibiotics in current clinical use. The pharmaceutical industry has largely abandoned these compounds in favor of large libraries of synthetic molecules because of difficulties in identifying new natural product antibiotics scaffolds. Advances in next-generation genome sequencing, bioinformatics, and analytical chemistry are combining to overcome barriers to natural products. Coupled with new strategies in antibiotic discovery, including inhibition of resistance, novel drug combinations, and new targets, natural products are poised for a renaissance to address what is a pressing health care crisis.

scholarly journals Co-culture of soil biofilm isolates enables the discovery of novel antibiotics

2018 ◽  
Author(s):  
Chun-Hui Gao ◽  
Peng Cai ◽  
Zhunjie Li ◽  
Yichao Wu ◽  
Qiaoyun Huang
Keyword(s):  
Bacterial Species ◽  
Gene Clusters ◽  
The Social ◽  
New Antibiotics ◽  
Interaction Strategy ◽  
Transcriptomic Changes ◽  
Antibiotic Discovery ◽  
Promising Source ◽  
Novel Antibiotics ◽  
Biofilm Community

AbstractBacterial natural products (NPs) are considered to be a promising source of drug discovery. However, the biosynthesis gene clusters (BGCs) of NP are not often expressed, making it difficult to identify them. Recently, the study of biofilm community showed bacteria may gain competitive advantages by the secretion of antibiotics, implying a possible way to screen antibiotic by evaluating the social behavior of bacteria. In this study, we have described an efficient workflow for novel antibiotic discovery by employing the bacterial social interaction strategy with biofilm cultivation, co-culture, transcriptomic and genomic methods. We showed that a biofilm dominant species, i.e. Pseudomonas sp. G7, which was isolated from cultivated soil biofilm community, was highly competitive in four-species biofilm communities, as the synergistic combinations preferred to exclude this strain while the antagonistic combinations did not. Through the analysis of transcriptomic changes in four-species co-culture and the complete genome of Pseudomonas sp. G7, we finally discovered two novel non-ribosomal polypeptide synthetic (NRPS) BGCs, whose products were predicted to have seven and six amino acid components, respectively. Furthermore, we provide evidence showing that only when Pseudomonas sp. G7 was co-cultivated with at least two or three other bacterial species can these BGC genes be induced, suggesting that the co-culture of the soil biofilm isolates is critical to the discovery of novel antibiotics. As a conclusion, we set a model of applying microbial interaction to the discovery of new antibiotics.

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