Lysozyme Resistance in Streptococcus suis Is Highly Variable and Multifactorial

Background: Streptococcus suis is an important infectious agent for pigs and occasionally for humans. The host innate immune system plays a key role in preventing and eliminating S. suis infections. One important constituent of the innate immune system is the protein lysozyme, which is present in a variety of body fluids and immune cells. Lysozyme acts as a peptidoglycan degrading enzyme causing bacterial lysis. Several pathogens have developed mechanisms to evade lysozyme-mediated killing. In the present study we compared the lysozyme sensitivity of various S. suis isolates and investigated the molecular basis of lysozyme resistance for this pathogen. Results: The lysozyme minimal inhibitory concentrations of a wide panel of S. suis isolates varied between 0.3 to 10 mg/ml. By inactivating the oatA gene in a serotype 2 and a serotype 9 strain, we showed that OatA-mediated peptidoglycan modification partly contributes to lysozyme resistance. Furthermore, inactivation of the murMN operon provided evidence that additional peptidoglycan crosslinking is not involved in lysozyme resistance in S. suis. Besides a targeted approach, we also used an unbiased approach for identifying factors involved in lysozyme resistance. Based on whole genome comparisons of a lysozyme sensitive strain and selected lysozyme resistant derivatives, we detected several single nucleotide polymorphisms (SNPs) that were correlated with the lysozyme resistance trait. Two SNPs caused defects in protein expression of an autolysin and a capsule sugar transferase. Analysis of specific isogenic mutants, confirmed th

Gut mucosal DAMPs in IBD: From mechanisms to therapeutic implications

Endogenous damage-associated molecular patterns (DAMPs) are released during tissue damage and have increasingly recognized roles in the etiology of many human diseases. The inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), are immune-mediated conditions where high levels of DAMPs are observed. DAMPs such as calprotectin (S100A8/9) have an established clinical role as a biomarker in IBD. In this review, we use IBD as an archetypal common chronic inflammatory disease to focus on the conceptual and evidential importance of DAMPs in pathogenesis and why DAMPs represent an entirely new class of targets for clinical translation. </p

Pneumococcal vaccination by general practitioners: an evaluation of current practice

During the first two years following registration of the 23-valent pneumococcal vaccine in Belgium, the numbers of doses administered were 166 and 211 per 10,000 inhabitants, representing a vaccination coverage of nearly 20% of the recommended target population as defined by the High Council for Public Health. The time course of vaccine use showed a seasonal variation with up to 74 and 85% of the doses administered from September through November in 1996 and 1997, respectively. Vaccination practices by general practitioners and the profile of the patients who received the pneumococcal vaccine were studied during the September through December period each year. Among the 18,236 patients included, 82% were above 60 years of age (mean age 69.5 years). The main indications for Vaccination were chronic bronchopulmonary disease (41%) and cardiovascular disorders (26%). Age as the sole criterion was mentioned for only 17% of vaccine recipients. Sixty percent of the patients received influenza vaccine concomitantly. The intensity of the mass media campaign correlated with the public awareness of the national recommendations. These observations provide insight into current practices for pneumococcal vaccination in Belgium and suggest opportunities for future vaccination campaigns. (C) 1999 Elsevier Science Ltd. All rights reserved