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.

Distribution and diversity of glycocin biosynthesis gene clusters beyond Firmicutes

Glycobiology ◽  
2020 ◽  
Author(s):  
Vaidhvi Singh ◽  
Alka Rao
Keyword(s):  
Disulfide Bonds ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Gene Clusters ◽  
Type I ◽  
Event Analysis ◽  
Bacterial Phyla ◽  
Spoilage Bacteria ◽  
Biosynthesis Gene ◽  
Promising Source

Abstract Glycocins are the ribosomally synthesized glycosylated bacteriocins discovered and characterized in Firmicutes, only. These peptides have antimicrobial activity against several pathogenic bacteria, including Streptococcus pyogenes , methicillin-resistant Staphylococcus aureus and food-spoilage bacteria Listeria monocytogenes. Glycocins exhibit immunostimulatory properties and make a promising source of new antibiotics and food preservatives akin to Nisin. Biochemical studies of Sublancin, Glycocin F, Pallidocin and ASM1 prove that the nested disulfide-bonds are essential for their bioactivities. Using in silico approach of genome mining coupled with manual curation, here we identify 220 new putative glycocin biosynthesis gene clusters (PGBCs) spread across 153 bacterial species belonging to seven different bacterial phyla. Based on gene composition, we have grouped these PGBCs into five distinct conserved cluster Types I–V. All experimentally identified glycocins belong to Type I PGBCs. From protein sequence based phylograms, tanglegrams, global similarity heat-maps and cumulative mutual information analysis, it appears that glycocins may have originated from closely related bacteriocins, whereas recruitment of cognate glycosyltransferases (GTs) might be an independent event. Analysis further suggests that GTs may have coevolved with glycocins in cluster-specific manner to define distinctive donor specificities of GTs or to contribute to glycocin diversity across these clusters. We further identify 162 hitherto unreported PGBCs wherein the corresponding product glycocins have three or less than three cysteines. Secondary structure predictions suggest that these putative glycocins may not form di-nested disulfide-bonds. Therefore, production of such glycocins in heterologous host Escherichia coli is feasible and may provide novel antimicrobial spectrum and or mechanism of action for varied applications.

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.

Novel Antibiotics from Marine Sources

2011 ◽  
Vol 4 (3) ◽  
pp. 1446-1461 ◽  
Author(s):  
E.A. Martis ◽  
G M Doshi ◽  
G V Aggarwal ◽  
P P Shanbhag
Keyword(s):  
Pharmaceutical Industry ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Terrestrial Life ◽  
New Antibiotics ◽  
Antibiotic Compounds ◽  
New Generation ◽  
Novel Antibiotics ◽  
Untapped Resource

With the emergence of newer diseases, resistant forms of infectious diseases and multi-drug resistant bacteria, it has become essential to develop novel and more effective antibiotics. Current antibiotics are obtained from terrestrial life or made synthetically from intermediates. The ocean represents virtually untapped resource from which novel antibiotic compounds can be discovered. It is the marine world that will provide the pharmaceutical industry with the next generation of antibiotics. Marine antibiotics are antibiotics obtained from marine organisms. Scientists have reported the discovery of various antibiotics from marine bacteria (aplasmomycin, himalomycins, and pelagiomycins), sponges (Ara C, variabillin, strobilin, ircinin-1, aeroplysin, 3,5-dibromo-4-hydroxyphenylacetamide), coelenterates (asperidol and eunicin), mollusks (laurinterol and pachydictyol), tunicates (geranylhydroquinone and cystadytins), algae (cycloeudesmol, aeroplysinin-1(+), prepacifenol and tetrabromoheptanone), worms (tholepin and 3,5-dibromo-4-hydroxybezaldehyde), and actinomycetes (marinomycins C and D). This indicates that the marine environment, representing approximately half of the global diversity, is an enormous resource for new antibiotics and this source needs to be explored for the discovery of new generation antibiotics. The present article provides an overview of various antibiotics obtained from marine sources.

scholarly journals Looking for the X Factor in Bacterial Pathogenesis: Association of orfX-p47 Gene Clusters with Toxin Genes in Clostridial and Non-Clostridial Bacterial Species

Toxins ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 19 ◽  
Author(s):  
Maria B. Nowakowska ◽  
François P. Douillard ◽  
Miia Lindström
Keyword(s):  
Gene Cluster ◽  
In Silico ◽  
Botulinum Neurotoxin ◽  
Bacterial Species ◽  
Gene Clusters ◽  
Bacterial Pathogenesis ◽  
Toxin Gene ◽  
Toxin Complex ◽  
Analytical Tools ◽  
Bacillus Isolate

The botulinum neurotoxin (BoNT) has been extensively researched over the years in regard to its structure, mode of action, and applications. Nevertheless, the biological roles of four proteins encoded from a number of BoNT gene clusters, i.e., OrfX1-3 and P47, are unknown. Here, we investigated the diversity of orfX-p47 gene clusters using in silico analytical tools. We show that the orfX-p47 cluster was not only present in the genomes of BoNT-producing bacteria but also in a substantially wider range of bacterial species across the bacterial phylogenetic tree. Remarkably, the orfX-p47 cluster was consistently located in proximity to genes coding for various toxins, suggesting that OrfX1-3 and P47 may have a conserved function related to toxinogenesis and/or pathogenesis, regardless of the toxin produced by the bacterium. Our work also led to the identification of a putative novel BoNT-like toxin gene cluster in a Bacillus isolate. This gene cluster shares striking similarities to the BoNT cluster, encoding a bont/ntnh-like gene and orfX-p47, but also differs from it markedly, displaying additional genes putatively encoding the components of a polymorphic ABC toxin complex. These findings provide novel insights into the biological roles of OrfX1, OrfX2, OrfX3, and P47 in toxinogenesis and pathogenesis of BoNT-producing and non-producing bacteria.

scholarly journals Salicylic Acid Biosynthesis and Metabolism: A Divergent Pathway for Plants and Bacteria

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 705
Author(s):  
Awdhesh Kumar Mishra ◽  
Kwang-Hyun Baek
Keyword(s):  
Salicylic Acid ◽  
Bacterial Species ◽  
Shikimate Pathway ◽  
Gene Clusters ◽  
Defense Responses ◽  
Biosynthetic Gene ◽  
Biosynthetic Enzyme ◽  
Biosynthetic Gene Clusters ◽  
Acid Biosynthesis ◽  
Common Precursor

Salicylic acid (SA) is an active secondary metabolite that occurs in bacteria, fungi, and plants. SA and its derivatives (collectively called salicylates) are synthesized from chorismate (derived from shikimate pathway). SA is considered an important phytohormone that regulates various aspects of plant growth, environmental stress, and defense responses against pathogens. Besides plants, a large number of bacterial species, such as Pseudomonas, Bacillus, Azospirillum, Salmonella, Achromobacter, Vibrio, Yersinia, and Mycobacteria, have been reported to synthesize salicylates through the NRPS/PKS biosynthetic gene clusters. This bacterial salicylate production is often linked to the biosynthesis of small ferric-ion-chelating molecules, salicyl-derived siderophores (known as catecholate) under iron-limited conditions. Although bacteria possess entirely different biosynthetic pathways from plants, they share one common biosynthetic enzyme, isochorismate synthase, which converts chorismate to isochorismate, a common precursor for synthesizing SA. Additionally, SA in plants and bacteria can undergo several modifications to carry out their specific functions. In this review, we will systematically focus on the plant and bacterial salicylate biosynthesis and its metabolism.

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 Metagenomic exploration of the marine sponge mycale hentscheli uncovers multiple polyketide-producing bacterial symbionts

2020 ◽  
Author(s):  
Mathew Storey ◽  
SK Andreassend ◽  
Joe Bracegirdle ◽  
Alistair Brown ◽  
Robert Keyzers ◽  
...  
Keyword(s):  
Marine Sponge ◽  
Bacterial Species ◽  
Gene Clusters ◽  
Taxonomic Diversity ◽  
Marine Sponges ◽  
Metagenomic Sequencing ◽  
Defensive Symbiosis ◽  
Long Read ◽  
Comprehensive Picture ◽  
Mycale Hentscheli

© 2020 Storey et al. Marine sponges have been a prolific source of unique bioactive compounds that are presumed to act as a deterrent to predation. Many of these compounds have potential therapeutic applications; however, the lack of efficient and sustainable synthetic routes frequently limits clinical development. Here, we describe a metag-enomic investigation of Mycale hentscheli, a chemically gifted marine sponge that pos-sesses multiple distinct chemotypes. We applied shotgun metagenomic sequencing, hybrid assembly of short-and long-read data, and metagenomic binning to obtain a comprehensive picture of the microbiome of five specimens, spanning three chemo-types. Our data revealed multiple producing species, each having relatively modest secondary metabolomes, that contribute collectively to the chemical arsenal of the holo-biont. We assembled complete genomes for multiple new genera, including two species that produce the cytotoxic polyketides pateamine and mycalamide, as well as a third high-abundance symbiont harboring a proteusin-type biosynthetic pathway that appears to encode a new polytheonamide-like compound. We also identified an additional 188 biosynthetic gene clusters, including a pathway for biosynthesis of peloruside. These re-sults suggest that multiple species cooperatively contribute to defensive symbiosis in M. hentscheli and reveal that the taxonomic diversity of secondary-metabolite-producing sponge symbionts is larger and richer than previously recognized. IMPORTANCE Mycale hentscheli is a marine sponge that is rich in bioactive small mol-ecules. Here, we use direct metagenomic sequencing to elucidate highly complete and contiguous genomes for the major symbiotic bacteria of this sponge. We identify complete biosynthetic pathways for the three potent cytotoxic polyketides which have previously been isolated from M. hentscheli. Remarkably, and in contrast to previous studies of marine sponges, we attribute each of these metabolites to a different producing mi-crobe. We also find that the microbiome of M. hentscheli is stably maintained among in-dividuals, even over long periods of time. Collectively, our data suggest a cooperative mode of defensive symbiosis in which multiple symbiotic bacterial species cooperatively contribute to the defensive chemical arsenal of the holobiont.

scholarly journals Bacterial secondary metabolite biosynthetic potential in soil varies with phylum, depth, and vegetation type

2019 ◽  
Author(s):  
Allison M. Sharrar ◽  
Alexander Crits-Christoph ◽  
Raphaël Méheust ◽  
Spencer Diamond ◽  
Evan P. Starr ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Vegetation Type ◽  
Bacterial Species ◽  
Gene Clusters ◽  
Metagenomic Sequencing ◽  
Soil Bacterial Diversity ◽  
Community Members ◽  
Clinical Value ◽  
Specialized Metabolites ◽  
Shallow Soils

AbstractBacteria isolated from soils are major sources of specialized metabolites, including antibiotics and other compounds with clinical value that likely shape interactions among microbial community members and impact biogeochemical cycles. Yet, isolated lineages represent a small fraction of all soil bacterial diversity. It remains unclear how the production of specialized metabolites varies across the phylogenetic diversity of bacterial species in soils, and whether the genetic potential for production of these metabolites differs with soil type. We sampled soils and saprolite from three sites in a northern California Critical Zone Observatory with varying vegetation and bedrock characteristics and used metagenomic sequencing and assembly to reconstruct 1,334 microbial genomes containing diverse biosynthetic gene clusters (BGCs) for secondary metabolite production. We obtained genomes for prolific producers of secondary metabolites, including novel groups within the Actinobacteria, Chloroflexi and candidate phylum Dormibactereota. Surprisingly, one genome of a Candidate Phyla Radiation bacterium encoded for a ribosomally synthesized linear azole/azoline-containing peptide, a capacity we found in other publicly available CPR bacterial genomes. Overall, bacteria with higher biosynthetic potential were enriched in shallow soils and grassland soils, with patterns of abundance of BGC type varying by taxonomy.

Colombian frogs: promising source of new antibiotics

2020 ◽  
Author(s):  
Esteban Alzate ◽  
Laura Mejía ◽  
Maria Clara Nuñez ◽  
Julie Benavides ◽  
David Galvis-Pareja ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
E Coli ◽  
Microdilution Method ◽  
Comparable Effect ◽  
Frog Species ◽  
New Antibiotics ◽  
Inhibition Zones ◽  
Human Use ◽  
Promising Source ◽  
Positive Controls

Abstract Background: In middle Magdalena of the Antioquia region, Colombia frog secretions have been used as antibacterial agents, the purpose of this study is to assess the antibacterial activity of six frog species secretions. Methods: the Kirby-Bauer and the microdilution methods were used to evaluate antibacterial activity of the frogs secretions against S. aureus and E. coli, using two positive controls, ampicillin and ciprofloxacin. Results: secretions of all six families showed inhibition zones, the concentration at which this zone was bigger was assayed later by the microdilution method and compared to ampicillin and ciprofloxacin. Only the secretion from the Phyllomedusidae exhibited a comparable effect to that one of control antibiotics. Conclusions: in here we provide evidence that secretions from local frogs have an antibacterial effect against two strains of bacteria, further studies are needed to identify the peptides in the secretions and a wider range of safe concentrations for human use.

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.

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