Tailocins are nano-scale phage tail-like protein complexes that can mediate antagonistic interactions between closely related bacterial species. While the capacity to produce R-type tailocin was found widely across Gammaproteobacteria, the production of F-type tailocins seems comparatively rare. In this study, we examined the freshwater isolate, Pragia fontium 24613, which can produce both R- and F-type tailocins. We investigated their inhibition spectrum, focusing on clinically relevant enterobacteria, and identified the associated tailocin gene cluster. Transmission electron microscopy confirmed that inactivation of the tape measure protein within the tailocin cluster disrupted R-tailocin production. Comparative analysis of Budviciaceae gene clusters showed high conservation of R-type tailocin genes, whereas F-type tailocin genes were found in only a few species, with little conservation. Our findings indicate a high prevalence of bacteriocin production among underexplored Enterobacteriales species. Detected tailocins showed potential as antimicrobials targeting clinically significant pathogens.
- Klíčová slova
- Antibiotics, Antimicrobial agent, Enterobacteria, Fonticin, Phage tail-like particle, Yersinia enterocolitica,
- MeSH
- antibakteriální látky farmakologie biosyntéza MeSH
- bakteriociny * genetika farmakologie MeSH
- bakteriofágy * genetika metabolismus MeSH
- Enterobacteriaceae * genetika metabolismus účinky léků MeSH
- fylogeneze MeSH
- multigenová rodina MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- bakteriociny * MeSH
In natural environments, antibiotics are important means of interspecies competition. At subinhibitory concentrations, they act as cues or signals inducing antibiotic production; however, our knowledge of well-documented antibiotic-based sensing systems is limited. Here, for the soil actinobacterium Streptomyces lincolnensis, we describe a fundamentally new ribosome-mediated signaling cascade that accelerates the onset of lincomycin production in response to an external ribosome-targeting antibiotic to synchronize antibiotic production within the population. The entire cascade is encoded in the lincomycin biosynthetic gene cluster (BGC) and consists of three lincomycin resistance proteins in addition to the transcriptional regulator LmbU: a lincomycin transporter (LmrA), a 23S rRNA methyltransferase (LmrB), both of which confer high resistance, and an ATP-binding cassette family F (ABCF) ATPase, LmrC, which confers only moderate resistance but is essential for antibiotic-induced signal transduction. Specifically, antibiotic sensing occurs via ribosome-mediated attenuation, which activates LmrC production in response to lincosamide, streptogramin A, or pleuromutilin antibiotics. Then, ATPase activity of the ribosome-associated LmrC triggers the transcription of lmbU and consequently the expression of lincomycin BGC. Finally, the production of LmrC is downregulated by LmrA and LmrB, which reduces the amount of ribosome-bound antibiotic and thus fine-tunes the cascade. We propose that analogous ABCF-mediated signaling systems are relatively common because many ribosome-targeting antibiotic BGCs encode an ABCF protein accompanied by additional resistance protein(s) and transcriptional regulators. Moreover, we revealed that three of the eight coproduced ABCF proteins of S. lincolnensis are clindamycin responsive, suggesting that the ABCF-mediated antibiotic signaling may be a widely utilized tool for chemical communication. IMPORTANCE Resistance proteins are perceived as mechanisms protecting bacteria from the inhibitory effect of their produced antibiotics or antibiotics from competitors. Here, we report that antibiotic resistance proteins regulate lincomycin biosynthesis in response to subinhibitory concentrations of antibiotics. In particular, we show the dual character of the ABCF ATPase LmrC, which confers antibiotic resistance and simultaneously transduces a signal from ribosome-bound antibiotics to gene expression, where the 5' untranslated sequence upstream of its encoding gene functions as a primary antibiotic sensor. ABCF-mediated antibiotic signaling can in principle function not only in the induction of antibiotic biosynthesis but also in selective gene expression in response to any small molecules targeting the 50S ribosomal subunit, including clinically important antibiotics, to mediate intercellular antibiotic signaling and stress response induction. Moreover, the resistance-regulatory function of LmrC presented here for the first time unifies functionally inconsistent ABCF family members involving antibiotic resistance proteins and translational regulators.
- Klíčová slova
- ABCF ATPase, Streptomyces, antibiotic biosynthesis, antibiotic resistance, antibiotic-mediated signaling, chemical communication, regulation of gene expression, ribosomal regulation, signal transduction, specialized metabolism,
- MeSH
- adenosintrifosfatasy metabolismus MeSH
- antibakteriální látky biosyntéza farmakologie MeSH
- bakteriální léková rezistence MeSH
- bakteriální proteiny genetika metabolismus MeSH
- linkomycin biosyntéza farmakologie MeSH
- methyltransferasy MeSH
- multigenová rodina MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům genetika metabolismus MeSH
- regulace genové exprese u bakterií účinky léků MeSH
- ribozomy metabolismus MeSH
- signální transdukce MeSH
- Streptomyces metabolismus MeSH
- transkripční faktory MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenosintrifosfatasy MeSH
- antibakteriální látky MeSH
- bakteriální proteiny MeSH
- linkomycin MeSH
- methyltransferasy MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům MeSH
- rRNA (adenosine-O-2'-)methyltransferase MeSH Prohlížeč
- transkripční faktory MeSH
Myxobacteria belong to a group of bacteria that are known for their well-developed communication system and synchronized or coordinated movement. This typical behavior of myxobacteria is mediated through secondary metabolites. They are capable of producing secondary metabolites belonging to several chemical classes with unique and wide spectrum of bioactivities. It is predominantly significant that myxobacteria specialize in mechanisms of action that are very rare with other producers. Most of the metabolites have been explored for their medical and pharmaceutical values while a lot of them are still unexplored. This review is an attempt to understand the role of potential metabolites produced by myxobacteria in different applications. Different myxobacterial metabolites have demonstrated antibacterial, antifungal, and antiviral properties along with cytotoxic activity against various cell lines. Beside their metabolites, these myxobacteria have also been discussed for better exploitation and implementation in different industrial sectors.
- MeSH
- antibakteriální látky biosyntéza MeSH
- Myxococcales * chemie metabolismus MeSH
- průmyslová mikrobiologie * trendy MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antibakteriální látky MeSH
INTRODUCTION: The emergence and spread of antibiotic resistance among pathogenic bacteria drives the search for alternative antimicrobial therapies. Bacteriocins represent a potential alternative to antibiotic treatment. In contrast to antibiotics, bacteriocins are peptides or proteins that have relatively narrow spectra of antibacterial activities and are produced by a wide range of bacterial species. Bacteriocins of Escherichia coli are historically classified as microcins and colicins, and, until now, more than 30 different bacteriocin types have been identified and characterized. AREAS COVERED: We performed bibliographical searches of online databases to review the literature regarding bacteriocins produced by E. coli with respect to their occurrence, bacteriocin role in bacterial colonization and pathogenicity, and application of their antimicrobial effect. EXPERT OPINION: The potential use of bacteriocins for applications in human and animal medicine and the food industry includes (i) the use of bacteriocin-producing probiotic strains, (ii) recombinant production in plants and application in food, and (iii) application of purified bacteriocins.
- Klíčová slova
- Antimicrobials, E. coli, Escherichia, Shigella, bacteriocin, colicin, diarrhea, microcin, probiotic, virulence,
- MeSH
- antibakteriální látky biosyntéza izolace a purifikace farmakologie MeSH
- bakteriociny biosyntéza izolace a purifikace farmakologie MeSH
- Escherichia coli metabolismus MeSH
- koliciny biosyntéza izolace a purifikace farmakologie MeSH
- lidé MeSH
- probiotika farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antibakteriální látky MeSH
- bakteriociny MeSH
- koliciny MeSH
- microcin MeSH Prohlížeč
Ecosystems worldwide are exposed to pollutants connected to the industrial production of pharmaceuticals. The objective of this study was to study the composition and characteristics of the soil microbial communities that had been exposed to long-term selection pressure caused by the industrial production of penicillin G. Soil samples from four sites among the penicillin G production plant were analysed using 16S rRNA profiling via Illumina MiSeq platform and were compared with the control samples from four sites outside the plant. Total metagenomic DNA from the impacted soil was also used for the preparation of E. coli T1R-based fosmid library which was consequently qualitatively tested for the presence of penicillin G acylase (PGA)-encoding genes using the method of sequence homology. Analyses of alpha diversity revealed that the long-term antibiotic presence in the soil significantly increased the microbial diversity and richness in terms of Shannon diversity index (p = 0.002) and Chao estimates (p = 0.004). Principal component analysis showed that the two types of communities (on-site and control) could be separated at the phylum, class and genus level. The on-site soil was enriched in Betaproteobacteria, Deltaproteobacteria, Gemmatimonadetes, Acidobacteria and Planctomycetia, while a significant decrease in Actinobacteria was observed. Metagenomic fosmid library revealed high hit rates in identifying PGAs (14 different genes identified) and confirmed the biotechnological potential of soils impacted by anthropogenic activity. This study offers new insights into the changes in microbial communities of soils exposed to anthropogenic activity as well as indicates that those soils may represent a hotspot for biotechnologically interesting targets.
- Klíčová slova
- Antibiotic contamination, Fosmid library, Industrial production, Metagenome, Microbial consortia, Penicillin G acylase,
- MeSH
- antibakteriální látky biosyntéza MeSH
- Bacteria klasifikace genetika izolace a purifikace metabolismus MeSH
- biodiverzita MeSH
- DNA bakterií genetika MeSH
- Escherichia coli genetika MeSH
- fylogeneze MeSH
- látky znečišťující půdu MeSH
- metagenom MeSH
- metagenomika MeSH
- mikrobiota * genetika MeSH
- průmyslová mikrobiologie MeSH
- půda MeSH
- půdní mikrobiologie * MeSH
- RNA ribozomální 16S genetika MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- DNA bakterií MeSH
- látky znečišťující půdu MeSH
- půda MeSH
- RNA ribozomální 16S MeSH
Proteins MiaA and MiaB catalyze sequential isopentenylation and methylthiolation, respectively, of adenosine residue in 37th position of tRNAXXA. The mia mutations were recently shown by us to affect secondary metabolism and morphology of Streptomyces. However, it remained unknown as to whether both or one of the aforementioned modifications is critical for colony development and antibiotic production. Here, we addressed this issue through analysis of Streptomyces albus J1074 strains carrying double miaAmiaB knockout or extra copy of miaB gene. The double mutant differed from wild-type and miaA-minus strains in severity of morphological defects, growth dynamics, and secondary metabolism. Introduction of extra copy of miaB gene into miaA mutant restored aerial mycelium formation to the latter on certain solid media. Hence, miaB gene might be involved in tRNA thiomethylation in the absence of miaA; either MiaA- or MiaB-mediated modification appears to be enough to support normal metabolic and morphological processes in Streptomyces.
- MeSH
- alkyltransferasy a aryltransferasy genetika MeSH
- antibakteriální látky biosyntéza MeSH
- bakteriální geny genetika MeSH
- bakteriální proteiny genetika MeSH
- fenotyp * MeSH
- genetická transkripce MeSH
- genetické testování metody MeSH
- mutace MeSH
- peroxid vodíku farmakologie MeSH
- posttranskripční úpravy RNA * MeSH
- RNA transferová metabolismus MeSH
- sekundární metabolismus účinky léků genetika MeSH
- Streptomyces účinky léků genetika růst a vývoj metabolismus MeSH
- sulfurtransferasy genetika MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alkyltransferasy a aryltransferasy MeSH
- antibakteriální látky MeSH
- bakteriální proteiny MeSH
- peroxid vodíku MeSH
- RNA transferová MeSH
- sulfurtransferasy MeSH
An agar well diffusion assay (AWDA) was used to isolate a high bacteriocin-producing strain with a broad spectrum of antibacterial activity, strain MXG-68, from Inner Mongolia traditional fermented koumiss. Lactobacillus plantarum MXG-68 was identified by morphological, biochemical, and physiological characteristics and 16S rDNA analysis. The production of antibacterial substance followed a growth-interrelated model, starting at the late lag phase of 4 h and arriving at a maximum value in the middle of the stationary phase at 24 h. Antibacterial activity was abolished or decreased in the presence of pepsin, chymotrypsin, trypsin, proteinase, and papain K. The results showed that antibacterial substances produced by L. plantarum MXG-68 were proteinaceous and could thus be classified as the bacteriocin, named plantaricin MXG-68. The molar mass of plantaricin MXG-68 was estimated to be 6.5 kDa, and the amino acid sequence of its N-terminal was determined to be VYGPAGIFNT. The mode of plantaricin MXG-68 action was determined to be bactericidal. Bacteriocin in cell-free supernatant (CFS) at pH 7 was stable at different temperatures (60 °C, 80 °C, 100 °C, 121 °C for 30 min; 4 °C and - 20 °C for 30 days), as well as at pH 2.0-10.0. Antibacterial activity maintained stable after treatment with organic solvents, surfactants, and detergents but increased in response to EDTA. Response surface methodology (RSM) revealed the optimum conditions of bacteriocin production in L. plantarum MXG-68, and the bacteriocin production in medium optimized by RSM was 26.10% higher than that in the basal MRS medium.
- Klíčová slova
- Bacteriocin, Characterization, Lactobacillus plantarum, Response surface methodology, Screening,
- MeSH
- antibakteriální látky biosyntéza chemie farmakologie MeSH
- bakteriociny biosyntéza chemie farmakologie MeSH
- fylogeneze MeSH
- kinetika MeSH
- kultivační média MeSH
- kumys mikrobiologie MeSH
- Lactobacillus plantarum chemie klasifikace fyziologie MeSH
- molekulová hmotnost MeSH
- potravinářská mikrobiologie MeSH
- RNA ribozomální 16S genetika MeSH
- sekvence aminokyselin MeSH
- stabilita proteinů MeSH
- Staphylococcus účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Čína MeSH
- Názvy látek
- antibakteriální látky MeSH
- bakteriociny MeSH
- kultivační média MeSH
- RNA ribozomální 16S MeSH
Spiramycin is a 16-membered macrolide antibiotic produced by Streptomyces ambofaciens and used in human medicine for the treatment of various respiratory tract and genital infections. Several impurities were detected in spiramycin-fermentation broth, especially impurities D and F, which decreased the separation-extraction yield and increased production cost. Dextrins, as the main carbon source, influence the accumulation of spiramycin and impurities. In this work, two types of dextrin from vendor Y and Z were compared to study their influences on spiramycin production. Our results showed that final spiramycin production with dextrin Z was enhanced twofold as compared with dextrin Y; however, the content of impurities F and D were higher with dextrin Z relative to dextrin Y. Several parameters (adenosine triphosphate, total sugar, reducing sugar, and reducing sugar to total sugar) were analyzed to reveal differences in the fermentation process. In vitro dextrin hydrolysis by amylase revealed structural differences in the two types of dextrin, and real-time quantitative polymerase chain reaction analyses showed that the transcription of srm7 and srm21 (involved in forosaminyl methylation) was enhanced and potentially related to the reduced formation of impurity F with dextrin Y. Furthermore, the srm20/srm33 ratio, representing flux balance of forosaminyl and mycarosyl, was ~ 1, implying that forosaminyl and mycarosyl biosynthesis were well balanced, resulting in reduced production of impurity D with dextrin Y.
The present study was performed to evaluate the antibacterial activities of an antimicrobial peptide (CSpK14) and the synergies thereof with β-lactams against vancomycin-resistant Staphylococcus aureus (VRSA) and Enterococci (VRE). Our strain was isolated from fermented food (kimchi), which is 99.79 % homologous with Bacillus amyloliquefaciens subsp. plantarum FZB42(T). CSpK14 was purified to homogeneity by diammonium sulfate precipitation, concentration, dialysis, and followed by two-stage chromatographic separation, i.e., Sepharose Cl-6B and Sephadex G-25 chromatography, and had a molar mass of ~4.6 kDa via Tricine SDS-PAGE and in situ examination. It was stable at pH 6.0-11.5 and temperature up to 80 °C. In addition, it was also stable with various metal ions, solvents, and proteases. The N-terminal amino acid sequence was H-Y-D-P-G-D-D-S-G-N-T-G and did not show any significant homology with reported peptides. However, it shows some degrees of identity with alpha-2-macroglobulin and ligand-gated channel protein from different microorganisms. CSpK14 significantly reduced the minimum inhibitory concentrations (MICs) of β-lactams and had no effect on non-β-lactams against VRSA and VRE. MICs of CSpK14/oxacillin and CSpK14/ampicillin were reduced by 8- to 64-fold and 2- to 16-fold, respectively. The time killing assay between CSpK14/oxacillin (2.29-2.37 Δlog10CFU/mL at 24 h) and CSpK14/ampicillin (2.30-2.38 Δlog10CFU/mL at 24 h) being >2-fold and fractional inhibitory concentration index ˂0.5 revealed synergy. Furthermore, the biofilms formed by VRSA and VRE were reduced completely. CSpK14 was simple to purify, had low molecular mass, was stable over a wide pH range or tested chemicals, had broad inhibitory spectrum, and possessed potent synergistic antimicrobial-antibiofilm properties. CSpK14 synergistically enhanced the efficacy of β-lactams and is therefore suitable for combination therapy.
- MeSH
- ampicilin farmakologie MeSH
- antibakteriální látky biosyntéza izolace a purifikace farmakologie MeSH
- Bacillus amyloliquefaciens klasifikace imunologie metabolismus MeSH
- biofilmy účinky léků růst a vývoj MeSH
- chromatografie iontoměničová MeSH
- enterokoky rezistentní vůči vankomycinu účinky léků růst a vývoj MeSH
- fylogeneze MeSH
- kationické antimikrobiální peptidy biosyntéza izolace a purifikace farmakologie MeSH
- kombinovaná farmakoterapie MeSH
- mikrobiální testy citlivosti MeSH
- oxacilin farmakologie MeSH
- rezistence na vankomycin účinky léků MeSH
- sekvence aminokyselin MeSH
- stabilita proteinů MeSH
- Staphylococcus aureus účinky léků růst a vývoj MeSH
- synergismus léků MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ampicilin MeSH
- antibakteriální látky MeSH
- kationické antimikrobiální peptidy MeSH
- oxacilin MeSH
This review aims at comparing some historical data with the current situation in the study of biogenesis of natural compounds, antibiotics in the first place. Biogenesis of tetracyclines and cycloheximide and related compounds serves as example. Examples of molecular biological and bioinformatics methods used in the study of antibiotic biogenesis are described both in terms of its historical aspects and the current knowledge.
- MeSH
- antibakteriální látky biosyntéza metabolismus MeSH
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- metabolické sítě a dráhy genetika MeSH
- objevování léků dějiny MeSH
- výpočetní biologie MeSH
- Check Tag
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- přehledy MeSH
- Názvy látek
- antibakteriální látky MeSH
