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Excretion of Escherichia coli α-hemolysin was tested in rough and smooth strains of Klebsiella pneumoniae and Salmonella typhimurium. Smooth strains harboring the hemolytic recombinant plasmid pANN202-312 showed a five- to tenfold increase in the hemolytic activity evaluated in the external medium compared with isogenic rough strains harboring the same plasmid. [ABSTRACT FROM AUTHOR]

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations., Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL)., Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events., Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations., (© 2019 S. Karger AG, Basel.)

Background: Alpha1-antitrypsin deficiency (AATD) is an underdiagnosed genetic disorder that results in early-onset emphysema due to low serum levels of alpha1-proteinase inhibitor (alpha1-PI), leading to increased activity of tissue-damaging neutrophil elastase. Clinical outcomes of AATD may be improved by administering alpha1-PI augmentation therapy. Here, we describe the design of the ongoing Study of ProlAstin-c Randomized Therapy with Alpha-1 augmentation (SPARTA), a phase 3 trial designed to evaluate progression of lung tissue loss in patients with severe AATD receiving human alpha1-PI (Prolastin(®)-C) versus placebo, using whole-lung computed tomography (CT) densitometry., Study Design: SPARTA is a randomized, placebo-controlled trial assessing the efficacy and safety of two separate doses of Prolastin-C (60 and 120 mg/kg) administered weekly over 3 years in patients aged 18-70 years with a diagnosis of AATD and clinical evidence of pulmonary emphysema. The primary measure of efficacy (change from baseline whole-lung 15th percentile lung density [PD15]) will be determined by CT lung densitometry measured at total lung capacity. Secondary efficacy variables will be the evaluation of severe chronic obstructive pulmonary disease exacerbations, as defined by American Thoracic Society/European Respiratory Society criteria, and PD15 of the basal lung region using CT densitometry. Adverse events will be collected and documented., Conclusions: The SPARTA trial is designed to evaluate the long-term (3-year) efficacy of 2 separate doses of Prolastin-C for the treatment of emphysema in patients with AATD. Protocol number: GTi1201., Clinical Trials Identifier: NCT01983241., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A microtitration plate, antibody capture, enzyme-linked immunosorbent assay was developed for detection of Aeromonas hydrophila serogroup 0:34. The assay uses a detector antibody which shows no cross-reactions with Aeromonas strains not belonging to serogroup 0:34 or non-Aeromonas competing organisms. The detector antibody is mixed with the sample and incubated for 1 h; it is then microcentrifuged and the supernatant (unabsorbed antibody) titered on a microtiter plate coated with A. hydrophila cells from serogroup 0:34. All A. hydrophila strains from serogroup 0:34 that we tested in this manner reacted strongly with the detector antibody. Also, by culturing and performing the immunoassay with the detector antibody we established and quantified the presence of A. hydrophila 0:34 on different samples.

Growth in pooled human body fluids [urine, serum and peritoneal dialysate (HPD)] modulated the expression of cell envelope antigens in virulent (serotype O1:K1) and avirulent (serotype O1:K66) Klebsiella pneumoniae strains. Marked variations in the outer membrane protein (OMP) and lipopolysaccharide (LPS) profiles were noted when broth-grown cells were compared with those of bacteria cultured in body fluids. In particular, for the O1:K1 serotype strain, growth in the latter resulted in: (a) the expression of at least five iron-regulated OMPs in the 74-87 kDa range, the pattern of which was medium dependent; (b) alterations in the migration of the LPS core polysaccharide; and (c) the reversion of isogenic O-:K+ and O-:K- mutants to the O+ phenotype after growth in fresh serum but not in heat-inactivated serum, urine or HPD. Similar results were obtained for the O1:K66 serotype, although no variation in the migration of the LPS core was noted. For both O1:K1 and O1:K66 serotypes, neither the surface exposure of O1 serotype LPS nor the production of K-antigen (capsular polysaccharide) was affected by growth in body fluids. No reversion of K- mutants to the K+ phenotype was observed. These data illustrate the phenotype flexibility of this opportunistic pathogen and emphasise the crucial role of the O- rather than the K-antigen in protecting K. pneumoniae from complement-mediated serum killing.

Bacteriophage 18 was previously isolated by multiplication in Aeromonas hydrophila. The bacteriophage receptor was shown to be the lipopolysaccharide (LPS), specifically the low MW polysaccharide fraction (LPS core oligosaccharide) A. hydrophila mutants, resistant to this phage were isolated and found to be devoid of LPS O antigen by several criteria and had alterations in the lipopolysaccharide core.

Isogenic non-encapsulated (K-) mutants (O1:K-) were obtained from several different Klebsiella pneumoniae O1:K1 serotype strains. By employing K. pneumoniae bacteriophages FC3-1, FC3-2, and bacteriophage phi 1, the bacterial surface receptors of which, are the O1-antigen of lipopolysaccharide and the K1 capsular polysaccharide (K1) respectively, the K1 polysaccharide was found to completely cover the O1 lipopolysaccharide molecules in each of the O1:K1 strains examined. Exposure of the O-antigen at the cell surface was only observed after growth in the presence of sub-minimum inhibitory concentrations of antibiotics. The implications of these findings for the design of vaccines for the prevention of Klebsiella infections is discussed.