Toxin-antitoxin (TA) systems are small genetic elements which encode toxin proteins that interfere with vital cellular functions. PepA1 and PepG1 toxin proteins, known also as SprA1 and SprG1, are type I TA. In Staphylococcus aureus (S. aureus), their expression without the antitoxin counterparts (SprA1AS and SprF1), is lethal to the pathogen. Molecular Dynamics (MD) simulation was performed for PepA1 and PepG1 to understand their dynamic state, conformational changes, and their toxicity. The protein structures were constructed and used for MD simulation and the conformational changes, stability, flexibility, fluctuations, hydrophobicity, and role of their dynamic state on function prediction were studied extensively by GROMACS MD simulation analysis tools. In silico study indicated that the PepA1 and PepG1 proteins change their structural conformation from an open to closed state where PepA1 conformational changes were faster (10 ns) than PepG1 (20 ns) while PepG1 exerted more stability and flexibility than PepA1. According to SASA values, PepG1 is more hydrophobic than the PepA1 and forms fewer hydrogen bonds than PepA1. The in vivo study with PepA1 and PepG1 proteins provided evidence that both the conformation changes between the open and closed states and the amino acid sequence are crucial for peptide toxicity.

• MeSH
• Antitoxins * metabolism   MeSH
• Bacterial Proteins genetics   metabolism   MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Humans MeSH
• Peptides metabolism   MeSH
• Staphylococcal Infections * genetics   MeSH
• Staphylococcus aureus metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

This study characterized five Cronobacter spp. and six Salmonella spp. strains that had been isolated from 155 samples of powdered infant formula (PIF) sold in Chile and manufactured in Chile and Mexico in 2018-2020. Two strains of Cronobacter sakazakii sequence type (ST) ST1 and ST31 (serotypes O:1 and O:2) and one strain of Cronobacter malonaticus ST60 (O:1) were identified. All Salmonella strains were identified as Salmonella Typhimurium ST19 (serotype O:4) by average nucleotide identity, ribosomal multilocus sequence typing (rMLST), and core genome MLST (cgMLST). The C. sakazakii and C. malonaticus isolates were resistant to cephalothin, whereas the Salmonella isolates were resistant to oxacillin and ampicillin. Nineteen antibiotic resistance genes were detected in the C. sakazakii and C. malonaticus isolates; the most prevalent were mcr-9.1, blaCSA , and blaCMA . In Salmonella, 30 genes encoding for aminoglycoside and cephalosporin resistance were identified, including aac(6')-Iaa, β-lactamases ampH, ampC1, and marA. In the Cronobacter isolates, 32 virulence-associated genes were detected by WGS and clustered as flagellar proteins, outer membrane proteins, chemotaxis, hemolysins, invasion, plasminogen activator, colonization, transcriptional regulator, survival in macrophages, use of sialic acid, and toxin-antitoxin genes. In the Salmonella strains, 120 virulence associated genes were detected, adherence, magnesium uptake, resistance to antimicrobial peptides, secretion system, stress protein, toxin, resistance to complement killing, and eight pathogenicity islands. The C. sakazakii and C. malonaticus strains harbored I-E and I-F CRISPR-Cas systems and carried Col(pHHAD28) and IncFIB(pCTU1) plasmids, respectively. The Salmonella strains harbored type I-E CRISPR-Cas systems and carried IncFII(S) plasmids. The presence of C. sakazakii and Salmonella in PIF is a health risk for infants aged less than 6 months. For this reason, sanitary practices should be reinforced for its production and retail surveillance.

• Publication type
• Journal Article MeSH

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
• Adenine Nucleotides metabolism   MeSH
• Bacteria growth & development   metabolism   MeSH
• Bacterial Proteins metabolism   MeSH
• Databases, Genetic MeSH
• Stress, Physiological physiology   MeSH
• Guanosine Pentaphosphate metabolism   MeSH
• Guanosine Tetraphosphate metabolism   MeSH
• Guanosine Triphosphate metabolism   MeSH
• Ligases metabolism   MeSH
• Pyrophosphatases metabolism   MeSH
• Gene Expression Regulation, Bacterial genetics   MeSH
• Signal Transduction MeSH
• Toxin-Antitoxin Systems physiology   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't 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
• Anti-Bacterial Agents pharmacology   MeSH
• Bacterial Proteins genetics   MeSH
• Enterococcus faecalis drug effects   genetics   isolation & purification   MeSH
• Enterococcus faecium drug effects   genetics   isolation & purification   MeSH
• Vancomycin-Resistant Enterococci classification   genetics   isolation & purification   MeSH
• Gram-Positive Bacterial Infections epidemiology   microbiology   MeSH
• Humans MeSH
• Plasmids genetics   MeSH
• Vancomycin Resistance genetics   MeSH
• Toxin-Antitoxin Systems genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

Kniha je reedicí čtyřsvazkové učebnice lékařské chemie Jana Horbaczewského (1854–1942), která původně vyšla v nakladatelství Grosman a Svoboda mezi lety 1904–1908. Nakladatelská anotace. Kráceno; První česká učebnice lékařské chemie, která vychází opět po 111 letech u příležitosti 165. výročí narození autora.

• Keywords
• chemie fyziologická,
• MeSH
• Chemistry, Inorganic MeSH
• Chemistry, Organic MeSH
• Publication type
• Monograph MeSH
• Textbook MeSH

• Conspectus
• Chemie. Mineralogické vědy
• NML Fields
• chemie, klinická chemie

• MeSH
• Anti-Bacterial Agents adverse effects   MeSH
• Bacteria growth & development   drug effects   MeSH
• Drug Resistance, Bacterial * drug effects   MeSH
• Biofilms drug effects   MeSH
• Guanosine Pentaphosphate MeSH
• Humans MeSH
• Quorum Sensing drug effects   MeSH
• SOS Response, Genetics drug effects   MeSH
• Toxin-Antitoxin Systems drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review 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
• Antitoxins genetics   immunology   metabolism   MeSH
• Bacterial Toxins genetics   immunology   metabolism   MeSH
• Biotechnology methods   trends   MeSH
• Cell Growth Processes genetics   immunology   MeSH
• Financing, Organized MeSH
• Protein Synthesis Inhibitors immunology   metabolism   MeSH
• Humans MeSH
• Microbiology trends   MeSH
• Molecular Biology methods   trends   MeSH
• Plasmids genetics   MeSH
• Ribonucleases genetics   immunology   toxicity   MeSH
• Ribosomes genetics   immunology   MeSH
• RNA genetics   immunology   toxicity   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Z původního textu, který v současné době skýtá nejdokonalejší přehled o tématu, byly přeloženy vybrané kapitoly. Úvod seznamuje s terminologií a chemickou podstatou antigenů a protilátek. Poté jsou probírány precipitační a inhibiční reakce, aglutinace a skupina pěti sérových faktorů, tvořících cytotoxický reakční systém, tzv. komplement. První část uzavírá pojednání o anafylaxi, alergii a o vlastnostech protilátek. Druhá část se zabývá metodami stanovení antigenů a křížovými reakcemi. Závěr uvádí speciální metody imunochemického výzkumu a jejich kombinace.

• MeSH
• Antigens MeSH
• Immunity MeSH
• Immunochemistry MeSH
• Antibodies MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• alergologie a imunologie
• biochemie

• MeSH
• Antitoxins MeSH
• Toxins, Biological MeSH
• Escherichia coli MeSH
• Complement System Proteins MeSH

• MeSH
• Allergy and Immunology MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• alergologie a imunologie