RESUMEN
Bacteria have diverse defenses against phages. In response, jumbo phages evade multiple DNA-targeting defenses by protecting their DNA inside a nucleus-like structure. We previously demonstrated that RNA-targeting type III CRISPR-Cas systems provide jumbo phage immunity by recognizing viral mRNA exported from the nucleus for translation. Here, we demonstrate that recognition of phage mRNA by the type III system activates a cyclic triadenylate-dependent accessory nuclease, NucC. Although unable to access phage DNA in the nucleus, NucC degrades the bacterial chromosome, triggers cell death, and disrupts phage replication and maturation. Hence, type-III-mediated jumbo phage immunity occurs via abortive infection, with suppression of the viral epidemic protecting the population. We further show that type III systems targeting jumbo phages have diverse accessory nucleases, including RNases that provide immunity. Our study demonstrates how type III CRISPR-Cas systems overcome the inaccessibility of jumbo phage DNA to provide robust immunity.
Asunto(s)
Bacteriófagos , Bacteriófagos/genética , Sistemas CRISPR-Cas , Núcleo Celular , Cromosomas Bacterianos , Endonucleasas , ARN MensajeroRESUMEN
BACKGROUND: Women with chronic kidney disease have an increased risk of maternal and fetal complications in pregnancy. Pre-pregnancy counselling is recommended but the format of the counselling process and the experience of the patient have never been assessed. This study examines the experience of women with chronic kidney disease attending pre-pregnancy counselling and evaluates their pregnancy outcomes. METHODS: This is a cross-sectional assessment of 179 women with chronic kidney disease attending a pre-pregnancy counselling clinic (2003-2011) with retrospective evaluation of aetiology, comorbidity, treatment and adverse pregnancy outcome compared with 277 hospital controls. It includes an analysis of descriptive data and free text content from 72 questionnaire responders. RESULTS: 65/72 (90%) of women found the clinic informative. 66 women (92%) felt that the consultation had helped them decide about pursuing pregnancy. 12 women (17%) found the multidisciplinary process intimidating. Free text comments supported the positive nature of the counselling experience, but also highlighted issues of access and emotional impact. Adverse pregnancy outcome rates were significantly higher in women with chronic kidney disease: 7/35 (20%) had pre-eclampsia (p < 0.001), 8/35 (23%) infants were small for gestational age (p < 0.001), 11/35 (31%) had preterm deliveries (<37 weeks) (p < 0.001) and 5/35 (14%) had a pregnancy loss compared with 4%, 10%, 8% and 3% of controls respectively. CONCLUSIONS: Women with a diverse range of renal disease severity and complexity attend pre-pregnancy counselling. Factors affecting pregnancy include hypertension, proteinuria and teratogenic medication. It is important to be able to inform women of the risks to them and their babies before pregnancy in order to facilitate informed-decision making. Most women with chronic kidney disease attending a pre-pregnancy counselling clinic report a positive experience.
Asunto(s)
Consejo Dirigido/métodos , Complicaciones del Embarazo/etiología , Resultado del Embarazo , Embarazo de Alto Riesgo , Atención Prenatal/métodos , Insuficiencia Renal Crónica/complicaciones , Adulto , Estudios Transversales , Femenino , Edad Gestacional , Humanos , Recién Nacido , Persona de Mediana Edad , Evaluación de Necesidades , Embarazo , Complicaciones del Embarazo/fisiopatología , Valores de Referencia , Insuficiencia Renal Crónica/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Reino Unido , Adulto JovenRESUMEN
In this Quick guide, Harding et al. introduce jumbo phages - the overlooked giants of the phage universe.