Search

Bacteriophages are an invaluable source of novel genetic diversity. Sequencing of phage genomes can reveal new proteins with potential uses as biotechnological and medical tools, and help unravel the diversity of biological mechanisms employed by phages to take over the host during viral infection. Aiming to expand the available collection of phage genomes, we have isolated, sequenced, and assembled the genome sequences of four phages that infect the clinical pathogen Klebsiella pneumoniae: vB_KpnP_FBKp16, vB_KpnP_FBKp27, vB_KpnM_FBKp34, and Jumbo phage vB_KpnM_FBKp24. The four phages show very low (0-13%) identity to genomic phage sequences deposited in the GenBank database. Three of the four phages encode tRNAs and have a GC content very dissimilar to that of the host. Importantly, the genome sequences of the phages reveal potentially novel DNA packaging mechanisms as well as distinct clades of tubulin spindle and nucleus shell proteins that some phages use to compartmentalize viral replication. Overall, this study contributes to uncovering previously unknown virus diversity, and provides novel candidates for phage therapy applications against antibiotic-resistant K. pneumoniae infections., (© The Author(s) 2021. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

CRISPR-Cas systems require discriminating self from non-self DNA during adaptation and interference. Yet, multiple cases have been reported of bacteria containing self-targeting spacers (STS), i.e. CRISPR spacers targeting protospacers on the same genome. STS has been suggested to reflect potential auto-immunity as an unwanted side effect of CRISPR-Cas defense, or a regulatory mechanism for gene expression. Here we investigated the incidence, distribution, and evasion of STS in over 100 000 bacterial genomes. We found STS in all CRISPR-Cas types and in one fifth of all CRISPR-carrying bacteria. Notably, up to 40% of I-B and I-F CRISPR-Cas systems contained STS. We observed that STS-containing genomes almost always carry a prophage and that STS map to prophage regions in more than half of the cases. Despite carrying STS, genetic deterioration of CRISPR-Cas systems appears to be rare, suggesting a level of escape from the potentially deleterious effects of STS by other mechanisms such as anti-CRISPR proteins and CRISPR target mutations. We propose a scenario where it is common to acquire an STS against a prophage, and this may trigger more extensive STS buildup by primed spacer acquisition in type I systems, without detrimental autoimmunity effects as mechanisms of auto-immunity evasion create tolerance to STS-targeted prophages., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: Colonoscopic surveillance is recommended for individuals with familial colorectal cancer (CRC). However, the appropriate screening interval has not yet been determined. The aim of this randomized trial was to compare a 3-year with a 6-year screening interval., Patients and Methods: Individuals between ages 45 and 65 years with one first-degree relative with CRC age < 50 years or two first-degree relatives with CRC were selected. Patients with zero to two adenomas at baseline were randomly assigned to one of two groups: group A (colonoscopy at 6 years) or group B (colonoscopy at 3 and 6 years). The primary outcome measure was advanced adenomatous polyps (AAPs). Risk factors studied included sex, age, type of family history, and baseline endoscopic findings., Results: A total of 528 patients were randomly assigned (group A, n = 262; group B, n = 266). Intention-to-treat analysis showed no significant difference in the proportion of patients with AAPs at the first follow-up examination at 6 years in group A (6.9%) versus 3 years in group B (3.5%). Also, the proportion of patients with AAPs at the final follow-up examination at 6 years in group A (6.9%) versus 6 years in group B (3.4%) was not significantly different. Only AAPs at baseline was a significant predictor for the presence of AAPs at first follow-up. After correction for the difference in AAPs at baseline, differences between the groups in the rate of AAPs at first follow-up and at the final examination were statistically significant., Conclusion: In view of the relatively low rate of AAPs at 6 years and the absence of CRC in group A, we consider a 6-year surveillance interval appropriate. A surveillance interval of 3 years might be considered in patients with AAPs and patients with ≥ three adenomas., (© 2015 by American Society of Clinical Oncology.)