Prioritizing echocardiography in Staphylococcus aureus bacteraemia.

OBJECTIVES: Infective endocarditis (IE) is a severe complication in Staphylococcus aureus bacteraemia (SAB) and recent guidelines from the BSAC recommend all patients undergo echocardiography. We assessed the use of echocardiography at a major tertiary referral centre and sought to identify those patients most likely to have positive findings. METHODS: We retrospectively evaluated all cases of SAB at Oxford University Hospitals NHS Trust between September 2006 and August 2011. RESULTS: Three-hundred-and-six out of 668 patients with SAB underwent cardiac imaging on average 9.8 ± 1.3 days from the first culture. Thirty-one patients (10.1%) had echocardiographic evidence of IE. Risk factors for observing evidence of IE on scanning included the presence of prosthetic heart valves (32% versus 4%, P < 0.001) or cardiac rhythm management (CRM) devices (16% versus 3%, P < 0.004). On excluding patients with prosthetic valves or CRM devices from the analysis, no patient with a line-related bacteraemia and only one patient (an intravenous drug user) with no/mild regurgitation on transthoracic echocardiography had echo evidence of IE. CONCLUSIONS: We propose that the use of scarce echocardiography resources could be prioritized. Patients with prosthetic heart valves or a CRM device should receive early cardiological input and transoesophageal echocardiography. In patients with a clearly defined line-related bacteraemia who do not have a prosthetic valve or CRM device or clinical features of IE, response to treatment could be closely monitored and imaging deferred. Patients without a line-related infection or prosthetic valve/device could receive a transthoracic echocardiogram as a screening tool.

RecN protein and transcription factor DksA combine to promote faithful recombinational repair of DNA double-strand breaks.

In rapidly dividing bacterial cells, the machinery for repair of DNA double-strand breaks has to contend not only with the forces driving replication and transmission of the DNA but also its transcription. By exploiting I-SceI homing endonuclease to break the Escherichia coli chromosome at one or more defined locations, we have been able to investigate how these processes are co-ordinated and repair is accomplished. When breaks are induced at a single site, the SOS-inducible RecN protein and the transcription factor DksA combine to promote efficient repair. When induced at two or more, distantly located sites, RecN becomes almost indispensable. Many cells that do survive have extensive deletions of sequences flanking the break, with end points often coinciding with imperfect repeat elements. These findings herald a much greater complexity for chromosome repair than suggested by current mechanistic models and reveal a role for RecN in protecting the chromosome from break-induced chromosome rearrangements.

RecG helicase promotes DNA double-strand break repair.

Double-strand breaks pose a major threat to the genome and must be repaired accurately if structural and functional integrity are to be preserved. This is usually achieved via homologous recombination, which enables the ends of a broken DNA molecule to engage an intact duplex and prime synthesis of the DNA needed for repair. In Escherichia coli, repair relies on the RecBCD and RecA proteins, the combined ability of which to initiate recombination and form joint-molecule intermediates is well understood. To shed light on subsequent events, we exploited the I-SceI homing endonuclease of yeast to make breaks at I-SceI cleavage sites engineered into the chromosome. We show that survival depends on RecA and RecBCD, and that subsequent events can proceed via either of two pathways, one dependent on the RuvABC Holliday junction resolvase and the other on RecG helicase. Both pathways rely on PriA, presumably to facilitate DNA replication. We discuss the possibility that classical Holliday junctions may not be essential intermediates in repair and consider alternative pathways for RecG-dependent separation of joint molecules formed by RecA.