Relationship Between Quorum Sensing and Secretion Systems

Quorum sensing (QS) is a communication mechanism between bacteria that allows specific processes to be controlled, such as biofilm formation, virulence factor expression, production of secondary metabolites and stress adaptation mechanisms such as bacterial competition systems including secretion systems (SS). These SS have an important role in bacterial communication. SS are ubiquitous; they are present in both Gram-negative and Gram-positive bacteria and in Mycobacterium sp. To date, 8 types of SS have been described (T1SS, T2SS, T3SS, T4SS, T5SS, T6SS, T7SS, and T9SS). They have global functions such as the transport of proteases, lipases, adhesins, heme-binding proteins, and amidases, and specific functions such as the synthesis of proteins in host cells, adaptation to the environment, the secretion of effectors to establish an infectious niche, transfer, absorption and release of DNA, translocation of effector proteins or DNA and autotransporter secretion. All of these functions can contribute to virulence and pathogenesis. In this review, we describe the known types of SS and discuss the ones that have been shown to be regulated by QS. Due to the large amount of information about this topic in some pathogens, we focus mainly on Pseudomonas aeruginosa and Vibrio spp

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Global gene expression analysis of in vitro root formation in Medicago truncatula

Medicago truncatula Gaertn. can generate roots in vitro through the formation of root stem cells from leaf explants cultured with auxin. To identify key genes involved in the early processes of root initiation, we compared gene expression in root-forming cultures (RFC) enriched for root stem cells with non-root-forming cultures (NRFC) and untreated leaves using the Affymetrix Medicago GeneChip. Comparing RFC (at 1 week, before root primordium formation) to normal leaf tissue, we identified 904 and 993 up- and downregulated probe sets. Comparing RFC and NRFC, we identified 92 and 182 up- and downregulated probe sets. By comparing all the samples we identified a set of 76 and 42 probe sets up- and downregulated that may be crucial to root stem cell formation and subsequent root initiation. Upregulated probe sets in RFC include Arabidopsis orthologs that are involved in root stem cell formation and root initiation. To validate the GeneChip results, quantitative real-time RTPCR analysis was used to examine the expression of specific up- and downregulated genes, all of which positively correlated with the microarray data. We used bioinformatic tools developed to functionally annotate the Medicago genome array. This showed significant changes in metabolism, signalling and the expression of transcription factors including some with described roles in root organogenesis and other genes not previously linked to this process. This data facilitates the mapping of regulatory and metabolic networks in M. truncatula and provides candidates for further functional analysis of root initiation in vitro and in planta