The development of new antibiotics faces a severe crisis inter alia owing to a lack of innovative chemical scaffolds with activities against Gram‐negative and multiresistant pathogens. Herein, we ...report highly potent novel antibacterial compounds, the myxobacteria‐derived cystobactamids 1–3, which were isolated from Cystobacter sp. and show minimum inhibitory concentrations in the low μg mL−1 range. We describe the isolation and structure elucidation of three congeners as well as the identification and annotation of their biosynthetic gene cluster. By studying the self‐resistance mechanism in the natural producer organism, the molecular targets were identified as bacterial type IIa topoisomerases. As quinolones are largely exhausted as a template for new type II topoisomerase inhibitors, the cystobactamids offer exciting alternatives to generate novel antibiotics using medicinal chemistry and biosynthetic engineering.
Against multidrug resistance: A novel chemical scaffold with very pronounced activity against bacterial topoisomerases has been isolated from myxobacteria. Cystobactamid 919‐2, as the most active derivative, is a potent antibacterial agent against numerous pathogens, including some Gram‐negative species, such as E. coli and A. baumannii (see Scheme; rel and SC denote relaxed and supercoiled E. coli DNA, respectively).
Microbial genome mining for drug discovery and development has been accelerating in recent years, driven by technical advancements in genome sequencing, bioinformatics, metabolomics/metabologenomics, ...and synthetic biology. Microbial genome mining is a multistep process that starts with the sequencing of microbes that encode multiple secondary metabolites and identifying new and novel secondary metabolite biosynthetic gene clusters (BGCs) to pursue. The initial steps in the process are critical for the overall success, and they encompass the most innovative new technologies to revitalize natural product discovery. As microbial genome mining has matured in recent years, unvalidated conjectures about what microbes to pursue, how to identify legitimate secondary metabolite BGCs, and how to sequence DNA to satisfactory levels of completion have been identified. The solutions to correct the misconceptions around these topics are beginning to be implemented.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
When considering microbial biotic interactions, viruses as well as eukaryotic grazers are known to be important components of aquatic microbial food webs. It might be the same for bacterivorous ...bacteria but these groups have been comparatively less studied. This is typically the case of the
and like organisms (BALOs), which are obligate bacterial predators of other bacteria. Recently, the abundance and distribution of three families of this functional group were investigated in perialpine lakes, revealing their presence and quantitative importance. Here, a more in-depth analysis is provided for Lake Geneva regarding the diversity of these bacterial predators at different seasons, sites and depths. We reveal a seasonal and spatial (vertical) pattern for BALOs. They were also found to be relatively diverse (especially
) and assigned to both known and unknown phylogenetic clusters. At last we found that most BALOs were positively correlated to other bacterial groups, mainly Gram-negative, in particular
(among which many are predators of other microbes). This study is the first shedding light on this potentially important bacterial killing group in a large and deep lake.
Myxobacteria are micropredators in the soil ecosystem with the capacity to move and feed cooperatively. Some myxobacterial strains have been used to control soil-borne fungal phytopathogens. However, ...interactions among myxobacteria, plant pathogens, and the soil microbiome are largely unexplored. In this study, we aimed to investigate the behaviors of the myxobacterium Corallococcus sp. strain EGB in the soil and its effect on the soil microbiome after inoculation for controlling cucumber Fusarium wilt caused by Fusarium oxysporum f. sp. cucumerinum (FOC).
A greenhouse and a 2-year field experiment demonstrated that the solid-state fermented strain EGB significantly reduced the cucumber Fusarium wilt by 79.6% (greenhouse), 66.0% (2015, field), and 53.9% (2016, field). Strain EGB adapted to the soil environment well and decreased the abundance of soil-borne FOC efficiently. Spatiotemporal analysis of the soil microbial community showed that strain EGB migrated towards the roots and root exudates of the cucumber plants via chemotaxis. Cooccurrence network analysis of the soil microbiome indicated a decreased modularity and community number but an increased connection number per node after the application of strain EGB. Several predatory bacteria, such as Lysobacter, Microvirga, and Cupriavidus, appearing as hubs or indicators, showed intensive connections with other bacteria.
The predatory myxobacterium Corallococcus sp. strain EGB controlled cucumber Fusarium wilt by migrating to the plant root and regulating the soil microbial community. This strain has the potential to be developed as a novel biological control agent of soil-borne Fusarium wilt. Video abstract.
Herein, we describe the myxobacterial natural product Corramycin isolated from Corallococcus coralloides. The linear peptide structure contains an unprecedented (2R,3S)‐γ‐N‐methyl‐β‐hydroxy‐histidine ...moiety. Corramycin exhibits anti‐Gram‐negative activity against Escherichia coli (E. coli) and is taken up via two transporter systems, SbmA and YejABEF. Furthermore, the Corramycin biosynthetic gene cluster (BGC) was identified and a biosynthesis model was proposed involving a 12‐modular non‐ribosomal peptide synthetase/polyketide synthase. Bioinformatic analysis of the BGC combined with the development of a total synthesis route allowed for the elucidation of the molecule's absolute configuration. Importantly, intravenous administration of 20 mg kg−1 of Corramycin in an E. coli mouse infection model resulted in 100 % survival of animals without toxic side effects. Corramycin is thus a promising starting point to develop a potent antibacterial drug against hospital‐acquired infections.
Corramycin is a novel natural product produced by the myxobacterium Corallococcus coralloides. The structure, extraordinary total synthesis and biosynthesis of the antibiotic is described for the first time. Its promise as an in vivo septicemia model, the absence of cross‐resistance with commonly used antibiotic classes, and the lack of cytotoxicity make Corramycin a potential new drug in the fight against multidrug‐resistant pathogens.
Many microbes produce stress-resistant spores to survive unfavorable conditions 1–4 and enhance dispersal 1, 5. Cooperative behavior is integral to the process of spore formation in some species 3, ...6, but the degree to which germination of spore populations involves social interactions remains little explored. Myxococcus xanthus is a predatory soil bacterium that upon starvation forms spore-filled multicellular fruiting bodies that often harbor substantial diversity of endemic origin 7, 8. Here we demonstrate that germination of M. xanthus spores formed during fruiting-body development is a social process involving at least two functionally distinct social molecules. Using pairs of natural isolates each derived from a single fruiting body that emerged on soil, we first show that spore germination exhibits positive density dependence due to a secreted “public-good” germination factor. Further, we find that a germination defect of one strain under saline stress in pure culture is complemented by addition of another strain that germinates well in saline environments and mediates cheating by the defective strain. Glycine betaine, an osmo-protectant utilized in all domains of life, is found to mediate saline-specific density dependence and cheating. Density dependence in non-saline conditions is mediated by a distinct factor, revealing socially complex spore germination involving multiple social molecules.
•Microbial spore germination can be a cooperative, density-dependent social process•Myxococcus xanthus spore germination involves multiple public-good molecules•Glycine betaine mediates density dependence of germination under saline conditions•Glycine-betaine non-producers cheat to germinate more efficiently in mixed groups
Pande et al. demonstrate that germination of M. xanthus spores is a socially multifaceted process mediated by multiple diffusible public-good molecules.
The motility mechanism of certain prokaryotes has long been a mystery, since their motion, known as gliding, involves no external appendages. The physical principles behind gliding still remain ...poorly understood. Using myxobacteria as an example of such organisms, we identify here the physical principles behind gliding motility and develop a theoretical model that predicts a 2-regime behavior of the gliding speed as a function of the substrate stiffness. Our theory describes the elasto-capillary–hydrodynamic interactions between the membrane of the bacteria, the slime it secretes, and the soft substrate underneath. Defining gliding as the horizontal translation under zero net force, we find the 2-regime behavior is due to 2 distinct mechanisms of motility thrust. On mildly soft substrates, the thrust arises from bacterial shape deformations creating a flow of slime that exerts a pressure along the bacterial length. This pressure in conjunction with the bacterial shape provides the necessary thrust for propulsion. On very soft substrates, however, we show that capillary effects must be considered that lead to the formation of a ridge at the slime–substrate–air interface, thereby creating a thrust in the form of a localized pressure gradient at the bacterial leading edge. To test our theory, we perform experiments with isolated cells on agar substrates of varying stiffness and find the measured gliding speeds in good agreement with the predictions from our elasto-capillary–hydrodynamic model. The mechanisms reported here serve as an important step toward an accurate theory of friction and substrate-mediated interactions between bacteria proliferating in soft media.
A newly isolated alkaline protease-producing myxobacterium was isolated from soil. The strain was identified as
Pyxidicoccus
sp. S252 on the basis of 16S rRNA sequence analysis. The extracellular ...alkaline proteases produced by isolate S252 (PyCP) was optimally active in the pH range of 11.0–12.0 and temperature range of 40–50°C The zymogram of PyCP showed six caseinolytic protease bands. The proteases were stable in the pH range of 8.0–10.0 and temperature range of 40–50°C. The activity of PyCP was enhanced in the presence of Na
+
, Mg
2+
, Cu
2+
, Tween-20, and hydrogen peroxide (H
2
O
2
) (hydrogen peroxide), whereas in Triton X-100, glycerol, ethylenediaminetetraacetic acid (EDTA), and Co
2+
, it was stable. PyCP showed a potential in various applications. The addition of PyCP in the commercial detergent enhanced the wash performance of the detergent by efficiently removing the stains of tomato ketchup and coffee. PyCP efficiently hydrolyzed the gelatin layer on X-ray film to release the embedded silver. PyCP also showed potent dehairing of goat skin and also efficiently deproteinized sea shell waste indicating its application in chitin extraction. Thus, the results of the present study indicate that
Pyxidicoccus
sp. S252 proteases have the potential to be used as an ecofriendly replacement of chemicals in several industrial processes.
The antibiotic crisis: How bacterial predators can help Pérez, Juana; Contreras-Moreno, Francisco Javier; Marcos-Torres, Francisco Javier ...
Computational and structural biotechnology journal,
01/2020, Letnik:
18
Journal Article
Recenzirano
Odprti dostop
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Discovery of antimicrobials in the past century represented one of the most important advances in public health. Unfortunately, the massive use of these compounds in medicine and ...other human activities has promoted the selection of pathogens that are resistant to one or several antibiotics. The current antibiotic crisis is creating an urgent need for research into new biological weapons with the ability to kill these superbugs. Although a proper solution requires this problem to be addressed in a variety of ways, the use of bacterial predators is emerging as an excellent strategy, especially when used as whole cell therapeutic agents, as a source of new antimicrobial agents by awakening silent metabolic pathways in axenic cultures, or as biocontrol agents. Moreover, studies on their prey are uncovering mechanisms of resistance that can be shared by pathogens, representing new targets for novel antimicrobial agents. In this review we discuss potential of the studies on predator-prey interaction to provide alternative solutions to the problem of antibiotic resistance.
In the multifaceted soil habitat, predation is one of the most successful strategies for obtaining food. An example of prokaryotic predators is myxobacteria. Although the prey spectra of some ...myxobacteria have been the subject of numerous studies, these myxobacteria are usually rare in soils compared to other myxobacterial families. Consequently, predation assays featuring easily cultivable myxobacteria provide only limited information on the myxobacterial potential and their interactions with organisms in the soil. Therefore, the prey spectrum of representatives of more common families was tested and compared with members of the model family Myxococcaceae. In a newly developed assay, the extent of lysis was tested against various Gram-positive and Gram-negative bacteria, as well as four yeasts. It was shown that Kofleria flava and Haliangium ochraceum have an equally diverse prey spectrum as the model genera Myxococcus and Corallococcus. However, less well-studied myxobacteria often lyse the prey colonies to a larger extent. Yeasts were lysed just as efficiently as bacteria. Furthermore, it was tested whether different myxobacteria can inhibit the growth of filamentous fungi. Almost every strain was able to prevent the spread of at least one fungus. H. ochraceum showed the highest activity and inhibited all fungi, including plant pathogenic Fusarium. These multiple interactions together with the high relative abundance in situ, suggest that myxobacteria, especially understudied families, could have a more important role in the soil food web than previously thought. The individual interaction spectra of the different myxobacteria provide only a glimpse at the complex relationships between the organisms in soil, which still remain understudied.
•Myxobacteria lyse different yeasts, bacteria and inhibit fungal growth.•Species specific predation spectrum.•Myxobacteria add complexity to soil food webs.•Myxobacteria potentially affect bacterial and fungal energy channels simultaneously.•Haliangium ochraceum as microbial broad-spectrum predator.
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