RESUMEN
Horizontal gene transfer and mutation are the two major drivers of microbial evolution that enable bacteria to adapt to fluctuating environmental stressors1. Clustered, regularly interspaced, short palindromic repeats (CRISPR) systems use RNA-guided nucleases to direct sequence-specific destruction of the genomes of mobile genetic elements that mediate horizontal gene transfer, such as conjugative plasmids2 and bacteriophages3, thus limiting the extent to which bacteria can evolve by this mechanism. A subset of CRISPR systems also exhibit non-specific degradation of DNA4,5; however, whether and how this feature affects the host has not yet been examined. Here we show that the non-specific DNase activity of the staphylococcal type III-A CRISPR-Cas system increases mutations in the host and accelerates the generation of antibiotic resistance in Staphylococcus aureus and Staphylococcus epidermidis. These mutations require the induction of the SOS response to DNA damage and display a distinct pattern. Our results demonstrate that by differentially affecting both mechanisms that generate genetic diversity, type III-A CRISPR systems can modulate the evolution of the bacterial host.
Asunto(s)
Sistemas CRISPR-Cas/genética , Sistemas CRISPR-Cas/inmunología , Mutagénesis , Mutación , Staphylococcus/genética , Antibacterianos/farmacología , Bacteriófagos/clasificación , Bacteriófagos/fisiología , Proteínas Asociadas a CRISPR/metabolismo , ADN de Cadena Simple/genética , ADN de Cadena Simple/metabolismo , Desoxirribonucleasas/metabolismo , Farmacorresistencia Microbiana/efectos de los fármacos , Respuesta SOS en Genética/efectos de los fármacos , Staphylococcus/efectos de los fármacos , Staphylococcus/inmunología , Staphylococcus/virología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/virología , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/virología , Factores de TiempoRESUMEN
OBJECTIVE: To assess the usefulness of two definitions of acute clinical chorioamnionitis (ACCA) in predicting risk of neonatal infectious outcomes (NIO) and mortality, the first definition requiring maternal fever alone (Fever), and the second requiring ≥ 1 Gibbs criterion besides fever (Fever + 1). STUDY DESIGN: PubMed, Web of Science, and the Cochrane Database of Systematic Reviews were searched from January 1, 1979 to April 9, 2013. Twelve studies were reviewed (of 316 articles identified): three studies with term patients, four with preterm premature rupture of membranes (PPROM) patients, and five mixed studies with mixed gestational ages and/or membrane status (intact and/or ruptured). RESULTS: Both definitions demonstrated an increased NIO risk for ACCA versus non-ACCA patients, with an odds ratio increase for the Fever + 1 definition that was about twofold larger than the Fever definition. CONCLUSION: As the Fever definition demonstrated increased NIO risk for ACCA versus non-ACCA patients, the Fever alone ACCA definition should be used to trigger future clinical treatment in many clinical situations.