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
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