Suppression of Plant Resistance Gene-Based Immunity by a Fungal Effector

The innate immune system of plants consists of two layers. The first layer, called basal resistance, governs recognition of conserved microbial molecules and fends off most attempted invasions. The second layer is based on Resistance (R) genes that mediate recognition of effectors, proteins secreted by pathogens to suppress or evade basal resistance. Here, we show that a plant-pathogenic fungus secretes an effector that can both trigger and suppress R gene-based immunity. This effector, Avr1, is secreted by the xylem-invading fungus Fusarium oxysporum f.sp. lycopersici (Fol) and triggers disease resistance when the host plant, tomato, carries a matching R gene (I or I-1). At the same time, Avr1 suppresses the protective effect of two other R genes, I-2 and I-3. Based on these observations, we tentatively reconstruct the evolutionary arms race that has taken place between tomato R genes and effectors of Fol. This molecular analysis has revealed a hitherto unpredicted strategy for durable disease control based on resistance gene combinations

The Chaperone ClpX Stimulates Expression of Staphylococcus aureus Protein A by Rot Dependent and Independent Pathways

The Clp ATPases (Hsp100) constitute a family of closely related proteins that have protein reactivating and remodelling activities typical of molecular chaperones. In Staphylococcus aureus the ClpX chaperone is essential for virulence and for transcription of spa encoding Protein A. The present study was undertaken to elucidate the mechanism by which ClpX stimulates expression of Protein A. For this purpose, we prepared antibodies directed against Rot, an activator of spa transcription, and demonstrated that cells devoid of ClpX contain three-fold less Rot than wild-type cells. By varying Rot expression from an inducible promoter we showed that expression of Protein A requires a threshold level of Rot. In the absence of ClpX the Rot content is reduced below this threshold level, hence, explaining the substantially reduced Protein A expression in the clpX mutant. Experiments addressed at pinpointing the role of ClpX in Rot synthesis revealed that ClpX is required for translation of Rot. Interestingly, translation of the spa mRNA was, like the rot mRNA, enhanced by ClpX. These data demonstrate that ClpX performs dual roles in regulating Protein A expression, as ClpX stimulates transcription of spa by enhancing translation of Rot, and that ClpX additionally is required for full translation of the spa mRNA. The current findings emphasize that ClpX has a central role in fine-tuning virulence regulation in S. aureus

Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses

Highly pathogenic avian influenza (HPAI) H5N1 viruses cause severe infection in chickens at near complete mortality, but corresponding infection in ducks is typically mild or asymptomatic. To understand the underlying molecular differences in host response, primary chicken and duck lung cells, infected with two HPAI H5N1 viruses and a low pathogenicity avian influenza (LPAI) H2N3 virus, were subjected to RNA expression profiling. Chicken cells but not duck cells showed highly elevated immune and pro-inflammatory responses following HPAI virus infection. HPAI H5N1 virus challenge studies in chickens and ducks corroborated the in vitro findings. To try to determine the underlying mechanisms, we investigated the role of signal transducer and activator of transcription-3 (STAT-3) in mediating pro-inflammatory response to HPAIV infection in chicken and duck cells. We found that STAT-3 expression was down-regulated in chickens but was up-regulated or unaffected in ducks in vitro and in vivo following H5N1 virus infection. Low basal STAT-3 expression in chicken cells was completely inhibited by H5N1 virus infection. By contrast, constitutively active STAT-3 detected in duck cells was unaffected by H5N1 virus infection. Transient constitutively-active STAT-3 transfection in chicken cells significantly reduced pro-inflammatory response to H5N1 virus infection; on the other hand, chemical inhibition of STAT-3 activation in duck cells increased pro-inflammatory gene expression following H5N1 virus infection. Collectively, we propose that elevated pro-inflammatory response in chickens is a major pathogenicity factor of HPAI H5N1 virus infection, mediated in part by the inhibition of STAT-3

Anterolateral Ligament Expert Group consensus paper on the management of internal rotation and instability of the anterior cruciate ligament - deficient knee

Purpose of this paper is to provide an overview of the latest research on the anterolateral ligament (ALL) and present the consensus of the ALL Expert Group on the anatomy, radiographic landmarks, biomechanics, clinical and radiographic diagnosis, lesion classification, surgical technique and clinical outcomes. A consensus on controversial subjects surrounding the ALL and anterolateral knee instability has been established based on the opinion of experts, the latest publications on the subject and an exchange of experiences during the ALL Experts Meeting (November 2015, Lyon, France). The ALL is found deep to the iliotibial band. The femoral origin is just posterior and proximal to the lateral epicondyle; the tibial attachment is 21.6 mm posterior to Gerdy's tubercle and 4-10 mm below the tibial joint line. On a lateral radiographic view the femoral origin is located in the postero-inferior quadrant and the tibial attachment is close to the centre of the proximal tibial plateau. Favourable isometry of an ALL reconstruction is seen when the femoral position is proximal and posterior to the lateral epicondyle, with the ALL being tight upon extension and lax upon flexion. The ALL can be visualised on ultrasound, or on T2-weighted coronal MRI scans with proton density fat-suppressed evaluation. The ALL injury is associated with a Segond fracture, and often occurs in conjunction with acute anterior cruciate ligament (ACL) injury. Recognition and repair of the ALL lesions should be considered to improve the control of rotational stability provided by ACL reconstruction. For high-risk patients, a combined ACL and ALL reconstruction improves rotational control and reduces the rate of re-rupture, without increased postoperative complication rates compared to ACL-only reconstruction. In conclusion this paper provides a contemporary consensus on all studied features of the ALL. The findings warrant future research in order to further test these early observations, with the ultimate goal of improving the long-term outcomes of ACL-injured patients. Level of evidence Level V-Expert opinion