Serratia marcescens internalization and replication in human bladder epithelial cells

BACKGROUND: Serratia marcescens, a frequent agent of catheterization-associated bacteriuria, strongly adheres to human bladder epithelial cells in culture. The epithelium normally provides a barrier between lumal organisms and the interstitium; the tight adhesion of bacteria to the epithelial cells can lead to internalization and subsequent lysis. However, internalisation was not shown yet for S. marcescens strains. METHODS: Elektronmicroscopy and the common gentamycin protection assay was used to assess intracellular bacteria. Via site directed mutagenesis, an hemolytic negative isogenic Serratia strain was generated to point out the importance of hemolysin production. RESULTS: We identified an important bacterial factor mediating the internalization of S. marcescens, and lysis of epithelial cells, as the secreted cytolysin ShlA. Microtubule filaments and actin filaments were shown to be involved in internalization. However, cytolysis of eukaryotic cells by ShlA was an interfering factor, and therefore hemolytic-negative mutants were used in subsequent experiments. Isogenic hemolysin-negative mutant strains were still adhesive, but were no longer cytotoxic, did not disrupt the cell culture monolayer, and were no longer internalized by HEp-2 and RT112 bladder epithelial cells under the conditions used for the wild-type strain. After wild-type S. marcescens became intracellular, the infected epithelial cells were lysed by extended vacuolation induced by ShlA. In late stages of vacuolation, highly motile S. marcescens cells were observed in the vacuoles. S. marcescens was also able to replicate in cultured HEp-2 cells, and replication was not dependent on hemolysin production. CONCLUSION: The results reported here showed that the pore-forming toxin ShlA triggers microtubule-dependent invasion and is the main factor inducing lysis of the epithelial cells to release the bacteria, and therefore plays a major role in the development of S. marcescens infections

The Mediating Role of Street Code Attitudes on the Self-Control and Crime Relationship

Research has demonstrated strong but independent attention to the role of self-control and street code attitudes in predicting criminal and violent behavior. Yet, there are good theoretical notions to believe that street code attitudes may be a salient mechanism in the self-control–offending relationship. Specifically, the present study investigates: (1) the extent to which self-control predicts adopting street code attitudes and (2) whether street code attitudes mediate the effect of self-control on criminal behavior. Using data collected from a multisite sample of over 900 young adults, we assess this mediation hypothesis for three distinct types of criminal activity: violent, property, and drug use. Our results reveal that individuals with lower self-control are more likely to adopt street code attitudes, that self-control is related to all three forms of offending, and that street code attitudes fully mediate the effect of self-control on violence, partially on property crime, but not in the case of drug use. Findings and directions for future research are discussed.No Full Tex