Antibiotics from predatory bacteria Korp, Juliane; Vela Gurovic, María S; Nett, Markus
Beilstein journal of organic chemistry,
03/2016, Letnik:
12, Številka:
1
Journal Article
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Bacteria, which prey on other microorganisms, are commonly found in the environment. While some of these organisms act as solitary hunters, others band together in large consortia before they attack ...their prey. Anecdotal reports suggest that bacteria practicing such a wolfpack strategy utilize antibiotics as predatory weapons. Consistent with this hypothesis, genome sequencing revealed that these micropredators possess impressive capacities for natural product biosynthesis. Here, we will present the results from recent chemical investigations of this bacterial group, compare the biosynthetic potential with that of non-predatory bacteria and discuss the link between predation and secondary metabolism.
Tubulysin은 다양한 암세포주에 대해 강한 항암활성을 보이는 점액세균 유래 이차대사 생리활성물질이다. 본 연구에서는 tubulysin을 생산하는 두 균주의 점액세균 Archangium gephyra MEHO_002와 MEHO_004의 유전체 분석을 통해 tubulysin 생합성 유전자들로 추정되는 유전자군을 발견하였으며, 플라스미드 삽입에 의한 ...유전자 불활성화를 통해 이들 유전자들이 tubulysin 생산과 직접 연관되어 있음을 확인하였다. A. gephyra MEHO_002와 MEHO_004 균주의 tubulysin 생합성 유전자군(tubA~tubF)은 DNA 염기서열이 서로 97% 동일하였으며, 암호화하는 단백질들의 아미노산 서열도 서로 97-100% 유사하였다. MEHO_002와 MEHO_004 균주의 tubulysin 생합성 유전자군은 tubulysin 생산 점액세균으로 알려진 Cystobacter sp. SBCb004의 tubulysin 생합성 유전자군과 DNA 염기서열이 86% 동일하였다. 유전자군의 구성은 tubZ 유전자가 존재하지 않는다는 점을 제외하고는 SBCb004의 tubulysin 생합성 유전자군 구성과 동일하였다. 각 유전자가 암호화하는 단백질의 아미노산 서열은 Cystobacter sp. SBCb004의 tubulysin 생합성 유전자가 암호화하는 단백질들과 88-97% 유사하였으며, 각 단백질들의 도메인 구성도 동일하였다.
Tubulysins are a group of bioactive secondary metabolites from myxobacteria exhibiting strong anticancer activity against various cancer cell lines. In this study, we describe the identification of putative tubulysin biosynthetic gene clusters (tubA~tubF) in the genome sequences of two tubulysin-producing myxobacterial strains, Archangium gephyra MEHO_002 and MEHO_004. The inactivation of the putative tubulysin biosynthetic genes resulted in a tubulysin-production defect. The DNA sequences of the A. gephyra MEHO_002 and MEHO_004 tubulysin biosynthetic genes were 97% identical, and the amino acid sequences of the encoded proteins shared a similarity of 97-100%. The nucleotide sequences of the tubulysin biosynthetic gene clusters in MEHO_002 and MEHO_004 were 86% identical to that in Cystobacter sp. SBCb004 known as a tubulysin-producing myxobacterium, and the organization of the clusters was identical except for the lack of a tubZ gene in the clusters in MEHO_002 and MEHO_004. The amino acid sequences of the proteins encoded by each gene were 88-97% similar to those encoded by SBCb004, and the domain compositions of the proteins were also identical.
Myxobacteria have a complex life cycle and unique social behavior, and obtain nutrients by preying on bacteria and fungi in soil. Chitinase, β-1,3 glucanase and β-1,6 glucanase produced by ...myxobacteria can degrade the glycosidic bond of cell wall of some plant pathogenic fungi, resulting in a perforated structure in the cell wall. In addition, isooctanol produced by myxobacteria can lead to the accumulation of intracellular reactive oxygen species in some pathogenic fungi and induce cell apoptosis. Myxobacteria can also perforate the cell wall of some plant pathogenic oomycetes by β-1,3 glucanase, reduce the content of intracellular soluble protein and protective enzyme activity, affect the permeability of oomycete cell membrane, and aggravate the oxidative damage of pathogen cells. Small molecule compounds such as diisobutyl phthalate and myxovirescin produced by myxobacteria can inhibit the formation of biofilm and lipoprotein of bacteria, and cystobactamids can inhibit the activity of DNA gyrase, thus changing the permeability of bacterial cell membrane. Myxobacteria, as a new natural compound resource bank, can control plant pathogenic fungi, oomycetes and bacteria by producing carbohydrate active enzymes and small molecular compounds, so it has great potential in plant disease control.
•1. Whole genome sequencing and function annotation of a biocontrol Myxococcus xanthus R31.•2. Comparative genomic analysis of Myxococcus xanthus was revealed.•3 Provide new molecular insights of ...Myxococcus xanthus R31 and closely species.
Tomato bacterial wilt (TBW) caused by Ralstonia solanacearum is one of the most destructive soil-borne diseases. Myxococcus xanthus R31, isolated from healthy tomato rhizosphere soil using the R. solanacearum baiting method, exhibiting good biocontrol efficacy against TBW. However, the genomic information and evolutionary features of R31 are largely unclear. Here, the high-quality genome assembly of R31 was presented. Using Nanopore sequencing technology, we assembled the 9.25 Mb complete genome of R31 and identified several extracellular enzyme proteins, including carbohydrate-active enzymes (CAZymes) and peptidases. We also performed a comparative genome analysis of R31 and 17 other strains of M. xanthus with genome sequences in the NCBI database to gain insights into myxobacteria predation and genome size expansion. Average nucleotide identity and digital DNA-DNA hybridization calculation and phylogenetic analysis indicated that R31 was closely related to the species M. xanthus. Further comparative genomics analysis suggested that, in addition to characteristics of predatory microorganisms, R31 contains many strain-specific genes, which may provide a genetic basis for its proficient predatory ability. This study provides new insights into R31 and other closely related species and facilitates studies using genetic approaches to further elucidate the predation mechanism of myxobacteria.
Myxobacteria are special bacteria with wide adaptability, which are rich sources of structurally diverse natural products with intriguing biological properties. Here, a gram-negative myxobacterium ...strain s54d21 T was isolated from the sediment of a wetland park in China using the Escherichia coli baiting method. Based on 16S rRNA gene sequence and genomic data, the strain was demonstrated to be a novel species of a rare genus Hyalangium , designated Hyalangium ruber sp. nov (type strain s54d21 T = GDMCC 1.1945 T = JCM 39263 T ). The subsequent chemical investigation of the strain s54d21 T led to the isolation of three rare 3,5,6-trisubstituted 2(1 H )-pyrazinones, namely, hyalanones A–C ( 1 – 3 ), together with a known macrolactin A ( 4 ). Those new structures and their absolute configurations were unambiguously assigned by extensive analyses of spectroscopic data and density functional theory (DFT) calculations. In biological assays, compound 4 exhibited moderate cytotoxic activities against human cell lines RKO, A549, and NCM460 with IC 50 values ranging from 27.21 to 32.14 μ M.
Bacterial predation impacts microbial community structures, which can have both positive and negative effects on plant and animal health and on environmental sustainability.
is an epibiotic soil ...predator with a broad range of prey, including
, which establishes nitrogen-fixing symbiosis with legumes. During the
-
interaction, the predator must adapt its transcriptome to kill and lyse the target (predatosome), and the prey must orchestrate a transcriptional response (defensome) to protect itself against the biotic stress caused by the predatory attack. Here, we describe the transcriptional changes taking place in
in response to myxobacterial predation. The results indicate that the predator induces massive changes in the prey transcriptome with up-regulation of protein synthesis and secretion, energy generation, and fatty acid (FA) synthesis, while down-regulating genes required for FA degradation and carbohydrate transport and metabolism. The reconstruction of up-regulated pathways suggests that
modifies the cell envelop by increasing the production of different surface polysaccharides (SPSs) and membrane lipids. Besides the barrier role of SPSs, additional mechanisms involving the activity of efflux pumps and the peptide uptake transporter BacA, together with the production of H
O
and formaldehyde have been unveiled. Also, the induction of the iron-uptake machinery in both predator and prey reflects a strong competition for this metal. With this research we complete the characterization of the complex transcriptional changes that occur during the
-
interaction, which can impact the establishment of beneficial symbiosis with legumes.
Adjusting motility patterns according to environmental cues is important for bacterial survival.
, a bacterium moving on surfaces by gliding and twitching mechanisms, modulates the reversal frequency ...of its front-back polarity in response to mechanical cues like substrate stiffness and cell-cell contact. In this study, we propose that
's gliding machinery senses environmental mechanical cues during force generation and modulates cell reversal accordingly. To examine our hypothesis, we expand an existing mathematical model for periodic polarity reversal in
, incorporating the experimental data on the intracellular dynamics of the gliding machinery and the interaction between the gliding machinery and a key polarity regulator. The model successfully reproduces the dependence of cell reversal frequency on substrate stiffness observed in
gliding. We further propose reversal control networks between the gliding and twitching motility machineries to explain the opposite reversal responses observed in wild type
cells that possess both motility mechanisms. These results provide testable predictions for future experimental investigations. In conclusion, our model suggests that the gliding machinery in
can function as a mechanosensor, which transduces mechanical cues into a cell reversal signal.
Introduction
Natural products discovered from bacteria provide critically needed therapeutic leads for drug discovery, and myxobacteria are an established source for metabolites with unique chemical ...scaffolds and biological activities. Myxobacterial genomes accommodate an exceptional number and variety of biosynthetic gene clusters (BGCs) which encode for features involved in specialized metabolism.
Methods
In this study, we describe the collection, sequencing, and genome mining of 20 myxobacteria isolated from rhizospheric soil samples collected in North America.
Results
Nine isolates were determined to be novel species of myxobacteria including representatives from the genera
Archangium, Myxococcus, Nannocystis, Polyangium, Pyxidicoccus, Sorangium
, and
Stigmatella
. Growth profiles, biochemical assays, and descriptions were provided for all proposed novel species. We assess the BGC content of all isolates and observe differences between Myxococcia and Polyangiia clusters.
Discussion
Continued discovery and sequencing of novel myxobacteria from the environment provide BGCs for the genome mining pipeline. Utilizing complete or near-complete genome sequences, we compare the chromosomal organization of BGCs of related myxobacteria from various genera and suggest that the spatial proximity of hybrid, modular clusters contributes to the metabolic adaptability of myxobacteria.
Natural product discovery from microorganisms provided important sources for antibiotics, anti-cancer agents, immune-modulators, anthelminthic agents, and insecticides during a span of 50 years ...starting in the 1940s, then became less productive because of rediscovery issues, low throughput, and lack of relevant new technologies to unveil less abundant or not easily detected drug-like natural products. In the early 2000s, it was observed from genome sequencing that
Streptomyces
species encode about ten times as many secondary metabolites as predicted from known secondary metabolomes. This gave rise to a new discovery approach—microbial genome mining. As the cost of genome sequencing dropped, the numbers of sequenced bacteria, fungi and archaea expanded dramatically, and bioinformatic methods were developed to rapidly scan whole genomes for the numbers, types, and novelty of secondary metabolite biosynthetic gene clusters. This methodology enabled the identification of microbial taxa gifted for the biosynthesis of drug-like secondary metabolites. As genome sequencing technology progressed, the realities relevant to drug discovery have emerged, the conjectures and misconceptions have been clarified, and opportunities to reinvigorate microbial drug discovery have crystallized. This perspective addresses these critical issues for drug discovery.
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