The SseC translocon component in Salmonella enterica serovar Typhimurium is chaperoned by SscA

Background: Salmonella enterica is a causative agent of foodborne gastroenteritis and the systemic disease known as typhoid fever. This bacterium uses two type three secretion systems (T3SSs) to translocate protein effectors into host cells to manipulate cellular function. Salmonella pathogenicity island (SPI)-2 encodes a T3SS required for intracellular survival of the pathogen. Genes in SPI-2 include apparatus components, secreted effectors and chaperones that bind to secreted cargo to coordinate their release from the bacterial cell. Although the effector repertoire secreted by the SPI-2 T3SS is large, only three virulence-associated chaperones have been characterized. Results: Here we report that SscA is the chaperone for the SseC translocon component. We show that SscA and SseC interact in bacterial cells and that deletion of sscA results in a loss of SseC secretion, which compromises intracellular replication and leads to a loss of competitive fitness in mice. Conclusions: This work completes the characterization of the chaperone complement within SPI-2 and identifies SscA as the chaperone for the SseC translocon

RpoE fine tunes expression of a subset of SsrB-regulated virulence factors in Salmonella enterica serovar Typhimurium

<p>Abstract</p> <p>Background</p> <p>The survival of <it>Salmonella enterica </it>within the intracellular host niche requires highly co-ordinated expression of virulence effectors predominantly regulated by the SsrAB two-component regulatory system. <it>S. enterica </it>serovar Typhimurium mutants lacking the <it>ssrAB </it>genes are avirulent in mice, highlighting the importance of this regulatory system <it>in vivo</it>. Mutants lacking the gene encoding the alternative sigma factor σ^E(<it>rpoE</it>) are also highly attenuated for intracellular survival, pointing to a potential connection with the SsrAB regulatory system.</p> <p>Results</p> <p>In this study we demonstrate that RpoE is involved in fine-tuning the expression of a subset of SsrB-regulated genes found in the <it>Salmonella </it>pathogenicity island-2 (SPI-2) genetic locus that encodes a horizontally acquired type III secretion system, and unlinked genes integrated into this regulon that are required for virulence in host animals.</p> <p>Conclusion</p> <p>These data point to a potential connection between the virulence phenotype of strains lacking <it>ssrB </it>and <it>rpoE</it>, and highlight new transcriptional regulation that might be essential for appropriate temporal and spatial control of the virulence-associated type III secretion system during host infection.</p

Bilateral Cervical Dysfunction in Patients With Unilateral Lateral Epicondylalgia Without Concomitant Cervical or Upper Limb Symptoms: A Cross-Sectional Case-Control Study

Objective: The purposes of this study were to examine the prevalence and distribution of spinal and neurodynamic dysfunction in a population with unilateral lateral epicondylalgia (LE) without concomitant cervical or upper limb symptoms, compare with cervical examination in a healthy control population, and investigate potential associations with clinical and demographic factors. Methods: This cross-sectional study included 165 patients with LE along with 62 healthy controls. Manual examination (C4-T2) was performed by an unblinded examiner with dysfunction defined as pain of 3 or higher on a numerical rating scale in the presence of a severe or moderate hypomobility or hypermobility. Neurodynamic testing (radial nerve) was classified positive if LE symptoms were reproduced and altered by sensitization maneuver. Repeated-measures analysis of variance was used to compare sides, segmental levels, and groups. Regression analysis was used to determine associations between variables. Results: Thirty-six percent of patients had dysfunction of at least 1 spinal palpation site, and 41% had a positive neurodynamic test. Significant group-by-level (P = .02) and group-by-side (P = .04) interactions were found for spinal examination, with greater dysfunction bilaterally at C4-7 (P < .01) in LE compared with control arms. The number of positive palpation sites was associated with injury duration (P = .03), whereas neurodynamic response was associated with severity of resting pain (P = .04). Conclusions: Cervical dysfunction is evident in individuals with LE without obvious neck pain and may reflect central sensitization mechanisms. Further study of the nature of the relationship between cervical dysfunction and LE is required

Thermal hyperalgesia distinguishes those with severe pain and disability in unilateral lateral epicondylalgia

Objectives: To evaluate if sensory, motor, and psychological factors are different in severe lateral epicondylalgia compared with less severe cases and control

The non-motile phenotype of Salmonella hha ydgT mutants is mediated through PefI-SrgD

<p>Abstract</p> <p>Background</p> <p>Two ancestral nucleoid-associated proteins called Hha and YdgT contribute to the negative regulation of several virulence-associated genes in <it>Salmonella enterica </it>serovar Typhimurium. Our previous work showed that Hha and YdgT proteins are required for negative regulation of <it>Salmonella </it>Pathogenicity Island-2 and that <it>hha ydgT </it>double mutants are attenuated for murine infection. Interestingly, <it>hha ydgT </it>mutant bacteria exhibited a non-motile phenotype suggesting that Hha and YdgT have a role in flagellar regulation.</p> <p>Results</p> <p>In this study we show that the non-motile phenotype of <it>hha ydgT </it>mutants is due to decreased levels of the master transcriptional regulator FlhD₄C₂resulting in down-regulation of class II/III and class III flagellar promoters and lack of surface flagella on these cells. The horizontally acquired <it>pefI-srgD </it>region was found to be partially responsible for this phenotype since deletion of <it>pefI-srgD </it>in a <it>hha ydgT </it>deletion background resulted in transient restoration of class II/III and III transcription, expression of surface flagella, and motility in the quadruple mutant.</p> <p>Conclusion</p> <p>These data extend our current understanding of the mechanisms through which Hha and YdgT regulate flagellar biosynthesis and further describe how <it>S</it>. Typhimurium has integrated horizontal gene acquisitions into ancestral regulatory networks.</p

Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial

Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain