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Aim: The association of standard 12-lead electrocardiogram (ECG) markers with benefits of the primary prophylactic implantable cardioverter-defibrillator (ICD) has not been determined in the contemporary era. We analysed traditional and novel ECG variables in a large prospective, controlled primary prophylactic ICD population to assess the predictive value of ECG in terms of ICD benefit. Methods and results: Electrocardiograms from 1477 ICD patients and 700 control patients (EU-CERT-ICD; non-randomized, controlled, prospective multicentre study; ClinicalTrials.gov Identifier: NCT02064192), who met ICD implantation criteria but did not receive the device, were analysed. The primary outcome was all-cause mortality. In ICD patients, the co-primary outcome of first appropriate shock was used. Mean follow-up time was 2.4 ± 1.1 years to death and 2.3 ± 1.2 years to the first appropriate shock. Pathological Q waves were associated with decreased mortality in ICD patients [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.35–0.84; P < 0.01] and patients with pathological Q waves had significantly more benefit from ICD (HR 0.44, 95% CI 0.21–0.93; P = 0.03). QTc interval increase taken as a continuous variable was associated with both mortality and appropriate shock incidence, but commonly used cut-off values, were not statistically significantly associated with either of the outcomes. Conclusion: Pathological Q waves were a strong ECG predictor of ICD benefit in primary prophylactic ICD patients. Excess mortality among Q wave patients seems to be due to arrhythmic death which can be prevented by ICD., EU-CERT-ICD The EU-CERT-ICD Study Investigators: Elena Arbelo, MD, Axel Bauer MD, Frieder Braunschweig MD PhD, Josep Brugada MD, PhD, David Conen MD, Iwona Cygankiewicz MD, Michael Dommasch MD, Christian Eick, MD, Panagiota Flevari MD, Tim Friede PhD, Jan Galuszka MD, Jim Hansen MD, Robert Hatala MD, Markus Harden PhD, Katerina Hnatkova PhD, Heikki V. Huikuri MD, Juhani M. Junttila, MD PhD, Stefan Kääb MD, Gabriela Kaliska MD, Jaroslaw D. Kasprzak MD, Andreas Katsimardos MD, Milan Kozak MD, Tomasz Kuczejko MD, Andrzej Lubinski MD, Jozef Martinek PhD, Béla Merkely MD, PhD, Tomáš Novotný MD, Marek Malik PhD MD, Peter Perge MD, Burkert Pieske MD, Pyotr Platonov MD PhD, Pawel Ptaczyński, MD, Dariusz Qavoq MD, L. Rotkvić, MD, Zoltan Sallo MD, Simon Schlögl MD, Georg Schmidt MD, Moritz Sinner, MD, Rajeeva Sritharan MSc, Stefan Stefanow MD, Christian Sticherling MD PhD, Jesper Hastrup Svendsen MD DMSc, Martin Svetlosak MD, Janko Szavits-Nossan MD, Milos Taborsky MD, Anton Tuinenburg, MD, Bert Vandenberk MD, Marc A. Vos PhD, Rik Willems MD PhD, Stefan N Willich MD PhD, Christian Wolpert MD, Markus Zabel MD, Ante Anic, MD, Zoran Bakotic MD, Steffen Behrens MD, Dieter Bimmel MD, Sandro Brusich MD, Rüdiger Dissmann MD, Gerian Grönefeld, MD, Przemyzlav Guzik MD, Svetoslav Iovev MD, Zrinka Jurisic MD, Thomas Klingenheben, MD, Nikola Pavlović MD, Joachim Seegers MD, Robert H.G. Schwinger MD, Tchavdar Shalganov MD, Vassil Traykov MD, Vasil Velchev MD.

Conjugative elements are widespread in bacteria and include plasmids and integrative and conjugative elements (ICEs). They transfer from donor to recipient cells via an element-encoded type IV secretion system. These elements interact with and utilize host functions for their lifecycles. We sought to identify essential host genes involved in the lifecycle of the integrative and conjugative element ICEBs1 of Bacillus subtilis. We constructed a library of strains for inducible knockdown of essential B. subtilis genes using CRISPR interference. Each strain expressed one guide RNA in ICEBs1. We induced partial interference of essential genes and identified those that caused an acute defect in acquisition of ICEBs1 by recipient cells. This screen revealed that reducing expression of genes needed for synthesis of cell wall teichoic acids caused a decrease in conjugation. Using three different ways to reduce their synthesis, we found that wall teichoic acids were necessary in both donors and recipients for efficient conjugative transfer of ICEBs1. Further, we found that depletion of wall teichoic acids caused cells involved in ICEBs1 conjugation to die, most likely from damage to the cell envelope. Our results indicate that wall teichoic acids help protect against envelope stress caused by active conjugation machines.

Most bacterial genomes contain horizontally acquired and transmissible mobile genetic elements, including temperate bacteriophages and integrative and conjugative elements. Little is known about how these elements interact and co-evolved as parts of their host genomes. In many cases, it is not known what advantages, if any, these elements provide to their bacterial hosts. Most strains of Bacillus subtilis contain the temperate phage SPß and the integrative and conjugative element ICEBs1. Here we show that the presence of ICEBs1 in cells protects populations of B. subtilis from predation by SPß, likely providing selective pressure for the maintenance of ICEBs1 in B. subtilis. A single gene in ICEBs1 (yddK, now called spbK for SPß killing) was both necessary and sufficient for this protection. spbK inhibited production of SPß, during both activation of a lysogen and following de novo infection. We found that expression spbK, together with the SPß gene yonE constitutes an abortive infection system that leads to cell death. spbK encodes a TIR (Toll-interleukin-1 receptor)-domain protein with similarity to some plant antiviral proteins and animal innate immune signaling proteins. We postulate that many uncharacterized cargo genes in ICEs may confer selective advantage to cells by protecting against other mobile elements.

Most bacterial genomes contain horizontally acquired and transmissible mobile genetic elements, including temperate bacteriophages and integrative and conjugative elements. Little is known about how these elements interact and co-evolved as parts of their host genomes. In many cases, it is not known what advantages, if any, these elements provide to their bacterial hosts. Most strains of Bacillus subtilis contain the temperate phage SPß and the integrative and conjugative element ICEBs1. Here we show that the presence of ICEBs1 in cells protects populations of B. subtilis from predation by SPß, likely providing selective pressure for the maintenance of ICEBs1 in B. subtilis. A single gene in ICEBs1 (yddK, now called spbK for SPß killing) was both necessary and sufficient for this protection. spbK inhibited production of SPß, during both activation of a lysogen and following de novo infection. We found that expression spbK, together with the SPß gene yonE constitutes an abortive infection system that leads to cell death. spbK encodes a TIR (Toll-interleukin-1 receptor)-domain protein with similarity to some plant antiviral proteins and animal innate immune signaling proteins. We postulate that many uncharacterized cargo genes in ICEs may confer selective advantage to cells by protecting against other mobile elements.