Nejvíce citovaný článek - PubMed ID 11522828
Lytic bacteriophages are valuable therapeutic agents against bacterial infections. There is continual effort to obtain new phages to increase the effectivity of phage preparations against emerging phage-resistant strains. Here we described the genomic diversity of spontaneous host-range mutants of kayvirus 812. Five mutant phages were isolated as rare plaques on phage-resistant Staphylococcus aureus strains. The host range of phage 812-derived mutants was 42% higher than the wild type, determined on a set of 186 methicillin-resistant S. aureus strains representing the globally circulating human and livestock-associated clones. Comparative genomics revealed that single-nucleotide polymorphisms from the parental phage 812 population were fixed in next-step mutants, mostly in genes for tail and baseplate components, and the acquired point mutations led to diverse receptor binding proteins in the phage mutants. Numerous genome changes associated with rearrangements between direct repeat motifs or intron loss were found. Alterations occurred in host-takeover and terminal genomic regions or the endolysin gene of mutants that exhibited the highest lytic activity, which implied various mechanisms of overcoming bacterial resistance. The genomic data revealed that Kayvirus spontaneous mutants are free from undesirable genes and their lytic properties proved their suitability for rapidly updating phage therapeutics.
- MeSH
- bakteriální léková rezistence MeSH
- bakteriofágy genetika MeSH
- délka genomu MeSH
- genom virový MeSH
- genomika MeSH
- jednonukleotidový polymorfismus MeSH
- methicilin farmakologie MeSH
- mutace * MeSH
- Staphylococcus aureus růst a vývoj virologie MeSH
- zastoupení bazí MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- methicilin MeSH
Exfoliative toxin A (ETA)-coding temperate bacteriophages are leading contributors to the toxic phenotype of impetigo strains of Staphylococcus aureus. Two distinct eta gene-positive bacteriophages isolated from S. aureus strains which recently caused massive outbreaks of pemphigus neonatorum in Czech maternity hospitals were characterized. The phages, designated ϕB166 and ϕB236, were able to transfer the eta gene into a prophageless S. aureus strain which afterwards converted into an ETA producer. Complete phage genome sequences were determined, and a comparative analysis of five designed genomic regions revealed major variances between them. They differed in the genome size, number of open reading frames, genome architecture, and virion protein patterns. Their high mutual sequence similarity was detected only in the terminal regions of the genome. When compared with the so far described eta phage genomes, noticeable differences were found. Thus, both phages represent two new lineages of as yet not characterized bacteriophages of the Siphoviridae family having impact on pathogenicity of impetigo strains of S. aureus.
- MeSH
- DNA virů chemie genetika MeSH
- DNA viry genetika izolace a purifikace MeSH
- epidemický výskyt choroby MeSH
- exfoliatiny genetika MeSH
- fylogeneze MeSH
- genom virový * MeSH
- impetigo epidemiologie mikrobiologie MeSH
- infekce spojené se zdravotní péčí epidemiologie MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- novorozenec MeSH
- otevřené čtecí rámce MeSH
- polymorfismus délky restrikčních fragmentů MeSH
- pořadí genů MeSH
- porodnice MeSH
- přenos genů horizontální MeSH
- profágy klasifikace genetika izolace a purifikace MeSH
- sekvenční analýza DNA MeSH
- sekvenční homologie MeSH
- shluková analýza MeSH
- stafylokokové bakteriofágy klasifikace genetika izolace a purifikace MeSH
- stafylokokové infekce epidemiologie mikrobiologie MeSH
- Staphylococcus aureus izolace a purifikace virologie MeSH
- syntenie MeSH
- transdukce genetická MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- DNA virů MeSH
- exfoliatiny MeSH
BACKGROUND: The first systematic study of small non-coding RNAs (sRNA, ncRNA) in Streptomyces is presented. Except for a few exceptions, the Streptomyces sRNAs, as well as the sRNAs in other genera of the Actinomyces group, have remained unstudied. This study was based on sequence conservation in intergenic regions of Streptomyces, localization of transcription termination factors, and genomic arrangement of genes flanking the predicted sRNAs. RESULTS: Thirty-two potential sRNAs in Streptomyces were predicted. Of these, expression of 20 was detected by microarrays and RT-PCR. The prediction was validated by a structure based computational approach. Two predicted sRNAs were found to be terminated by transcription termination factors different from the Rho-independent terminators. One predicted sRNA was identified computationally with high probability as a Streptomyces 6S RNA. Out of the 32 predicted sRNAs, 24 were found to be structurally dissimilar from known sRNAs. CONCLUSION: Streptomyces is the largest genus of Actinomyces, whose sRNAs have not been studied. The Actinomyces is a group of bacterial species with unique genomes and phenotypes. Therefore, in Actinomyces, new unique bacterial sRNAs may be identified. The sequence and structural dissimilarity of the predicted Streptomyces sRNAs demonstrated by this study serve as the first evidence of the uniqueness of Actinomyces sRNAs.
- MeSH
- algoritmy MeSH
- bakteriální RNA chemie genetika MeSH
- druhová specificita MeSH
- genom bakteriální MeSH
- intergenová DNA MeSH
- konformace nukleové kyseliny MeSH
- molekulární modely MeSH
- nekódující RNA chemie genetika MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- Streptomyces coelicolor genetika MeSH
- Streptomyces genetika MeSH
- terminátorové oblasti (genetika) MeSH
- výpočetní biologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
- Názvy látek
- bakteriální RNA MeSH
- intergenová DNA MeSH
- nekódující RNA MeSH