Listeria monocytogenes is a major intracellular human foodborne bacterial pathogen. We previously revealed L. monocytogenes cadC as highly expressed during mouse infection. Here we show that L. monocytogenes CadC is a sequence-specific, DNA-binding and cadmium-dependent regulator of CadA, an efflux pump conferring cadmium resistance. CadC but not CadA is required for L. monocytogenes infection in vivo. Interestingly, CadC also directly represses lspB, a gene encoding a lipoprotein signal peptidase whose expression appears detrimental for infection. lspB overexpression promotes the release of the LpeA lipoprotein to the extracellular medium, inducing tumor necrosis factor α and interleukin 6 expression, thus impairing L. monocytogenes survival in macrophages. We propose that L. monocytogenes uses CadC to repress lspB expression during infection to avoid LpeA exposure to the host immune system, diminishing inflammatory cytokine expression and promoting intramacrophagic survival and virulence. CadC appears as the first metal efflux pump regulator repurposed during infection to fine-tune lipoprotein processing and host responses.
Background: Non-muscle myosin IIA is involved in force generation, movement, and membrane reshaping. Its activity is regulated by phosphorylation of the light chain. Results: NMHC-IIA head domain is tyrosine-phosphorylated by Src and modulates Listeria intracellular levels. Conclusion: Tyrosine phosphorylation of NMHC-IIA affects the outcome of infection. Significance: This novel post-translational modification of NMHC-IIA possibly affects its functions.
Given an undirected graph, the k -club problem seeks a maximum cardinality subset of nodes that induces a subgraph with diameter at most k . We present two new formulations for the 3-club problem: one is compact and the other has a nonpolynomial number of constraints. By defining an integer compact relaxation of the second formulation, we obtain a new upper bound on the 3-club optimum that improves on the 3-clique number bound. We derive new families of valid inequalities for the 3-club polytope and use them to strengthen the LP relaxations of the new models. The computational study is performed on 120 graphs with up to 200 nodes and edge densities reported in the literature to produce difficult instances of the 3-club problem. The results show that the new compact formulation is competitive with the exact solution methods reported in the literature, and that a large proportion of the LP gap is bridged with the new valid inequalities.
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