Under stressful conditions, bacterial RelA-SpoT Homolog (RSH) enzymes synthesize the alarmone (p)ppGpp, a nucleotide second messenger. (p)ppGpp rewires bacterial transcription and metabolism to cope with stress, and, at high concentrations, inhibits the process of protein synthesis and bacterial growth to save and redirect resources until conditions improve. Single-domain small alarmone synthetases (SASs) are RSH family members that contain the (p)ppGpp synthesis (SYNTH) domain, but lack the hydrolysis (HD) domain and regulatory C-terminal domains of the long RSHs such as Rel, RelA, and SpoT. We asked whether analysis of the genomic context of SASs can indicate possible functional roles. Indeed, multiple SAS subfamilies are encoded in widespread conserved bicistronic operon architectures that are reminiscent of those typically seen in toxin-antitoxin (TA) operons. We have validated five of these SASs as being toxic (toxSASs), with neutralization by the protein products of six neighboring antitoxin genes. The toxicity of Cellulomonas marina toxSAS FaRel is mediated by the accumulation of alarmones ppGpp and ppApp, and an associated depletion of cellular guanosine triphosphate and adenosine triphosphate pools, and is counteracted by its HD domain-containing antitoxin. Thus, the ToxSAS-antiToxSAS system with its multiple different antitoxins exemplifies how ancient nucleotide-based signaling mechanisms can be repurposed as TA modules during evolution, potentially multiple times independently.

• MeSH
• adeninnukleotidy metabolismus   MeSH
• Bacteria růst a vývoj   metabolismus   MeSH
• bakteriální proteiny metabolismus   MeSH
• databáze genetické MeSH
• fyziologický stres fyziologie   MeSH
• guanosinpentafosfát metabolismus   MeSH
• guanosintetrafosfát metabolismus   MeSH
• guanosintrifosfát metabolismus   MeSH
• ligasy metabolismus   MeSH
• pyrofosfatasy metabolismus   MeSH
• regulace genové exprese u bakterií genetika   MeSH
• signální transdukce MeSH
• systémy toxin-antitoxin fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• difterický antitoxin fyziologie   krev   MeSH
• difterický toxin fyziologie   krev   MeSH

• MeSH
• antitoxiny * MeSH
• biologické toxiny * MeSH
• imunizace * MeSH
• králíci * MeSH
• pyrogeny * MeSH
• spála * MeSH
• výzkum * MeSH
• Check Tag
• králíci * MeSH
• Publikační typ
• časopisecké články MeSH

Toxin-antitoxin systems (TAS) emerged more than 25 years ago and developed as an important field in molecular microbiology. TAS are autoregulated operons coding a stable toxin and an unstable antitoxin found in plasmids and chromosomes of Bacteria and Archaea. The conditional activation of their toxins interferes with cell growth/viability and, depending on the context, can influence plasmid maintenance, stress management, bacterial persistence, cell differentiation and, likely, bacterial virulence. This review summarizes recent results on the parD system of plasmid R1 and on the chromosomal relBE systems found in Escherichia coli and in Streptococcus pneumoniae with a focus on the RNase activity of their toxins, their regulation and their biomedical applications and implications.

• MeSH
• antitoxiny genetika   imunologie   metabolismus   MeSH
• bakteriální toxiny genetika   imunologie   metabolismus   MeSH
• biotechnologie metody   trendy   MeSH
• buňky - růstové procesy genetika   imunologie   MeSH
• financování organizované MeSH
• inhibitory syntézy proteinů imunologie   metabolismus   MeSH
• lidé MeSH
• mikrobiologie trendy   MeSH
• molekulární biologie metody   trendy   MeSH
• plazmidy genetika   MeSH
• ribonukleasy genetika   imunologie   toxicita   MeSH
• ribozomy genetika   imunologie   MeSH
• RNA genetika   imunologie   toxicita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• botulinový antitoxin MeSH
• botulotoxiny MeSH
• Clostridium botulinum MeSH
• Clostridium tetani MeSH
• farmakologie MeSH
• tetanový toxin MeSH
• tetanus MeSH
• Publikační typ
• abstrakt z konference MeSH

• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• farmacie a farmakologie
• toxikologie

Vancomycin-resistant enterococci (VRE) are nosocomial pathogens of increasing medical importance. This study involved 121 VRE selectively obtained from a representative set of 1464 samples collected from various sources in the north-eastern part of the Czech Republic. In total, 119 VRE belonged to Enterococcus faecium and two to Enterococcus faecalis. All isolates of E. faecium were resistant to at least three antibiotic classes. The resistance genes vanA, erm(B), tet(M), tet(L), aac(3)-IIIa and aac(6')-aph(2'') were detected. We assigned the E. faecium to sequence types ST5, ST18, ST38, ST64, ST92, ST273, ST549 and ST640. In E. faecium isolates, we identified the presence of replicases rep20pLG1 , rep2pRE25 , rep17pRUM , rep21pVEF1/2 and rep14pRI1 , as well as relaxases relpEF1 , relpLG1 , relpCIZ2 , relpRE25 and relpRUM . The presence of the toxin-antitoxin system axe-txe was detected mainly among isolates of hospital origin. The A and D types of transposon Tn1546 were those occurring most frequently. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first extensive study of vancomycin-resistant enterococci of diverse origin in a single well-defined area of the Czech Republic. The isolates were investigated for their antibiotic resistance, epidemiological characteristics and plasmid characteristics. Based on the results obtained, we can make assumptions as to the ways that vancomycin resistance is disseminated throughout the environment including humans and animals.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální proteiny genetika   MeSH
• Enterococcus faecalis účinky léků   genetika   izolace a purifikace   MeSH
• Enterococcus faecium účinky léků   genetika   izolace a purifikace   MeSH
• enterokoky rezistentní vůči vankomycinu klasifikace   genetika   izolace a purifikace   MeSH
• grampozitivní bakteriální infekce epidemiologie   mikrobiologie   MeSH
• lidé MeSH
• plazmidy genetika   MeSH
• rezistence na vankomycin genetika   MeSH
• systémy toxin-antitoxin genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

• MeSH
• antibakteriální látky škodlivé účinky   MeSH
• Bacteria růst a vývoj   účinky léků   MeSH
• bakteriální léková rezistence * účinky léků   MeSH
• biofilmy účinky léků   MeSH
• guanosinpentafosfát MeSH
• lidé MeSH
• quorum sensing účinky léků   MeSH
• SOS odpověď (genetika) účinky léků   MeSH
• systémy toxin-antitoxin účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• difterický antitoxin MeSH
• difterický toxin MeSH
• hemaglutinace MeSH
• imunita MeSH
• Geografické názvy
• Československo MeSH

• MeSH
• botulinový antitoxin aplikace a dávkování   MeSH
• botulismus diagnóza   etiologie   MeSH
• botulotoxiny otrava   MeSH
• Publikační typ
• kongresy MeSH