Alan S. Cross

Local and Disseminated Diseases Caused by Pseudomonas aeruginosa

Pseudomonas aeruginosa is an organism of relatively low virulence that rarely affects those with intact host defenses. In the immunocompromised host, however, it is capable of using a wide array of potential virulence factors to cause a variety of serious infections. P. aeruginosa (formerly Bacillus pyocyaneus) was originally isolated in pure culture by a French pharmacist named Gessard in 1882.1 The organism is ubiquitous in nature, has minimal growth requirements, is nutritionally versatile, and thrives in moist environments.2

Top down tandem mass spectrometric analysis of a chemically modified rough-type lipopolysaccharide vaccine candidate

AbstractRecent advances in lipopolysaccharide (LPS) biology have led to its use in drug discovery pipelines, including vaccine and vaccine adjuvant discovery. Desirable characteristics for LPS vaccine candidates include both the ability to produce a specific antibody titer in patients and a minimal host inflammatory response directed by the innate immune system. However, in-depth chemical characterization of most LPS extracts has not been performed; hence, biological activities of these extracts are unpredictable. Additionally, the most widely adopted workflow for LPS structure elucidation includes nonspecific chemical decomposition steps before analyses, making structures inferred and not necessarily biologically relevant. In this work, several different mass spectrometry workflows that have not been previously explored were employed to show proof-of-principle for top down LPS primary structure elucidation, specifically for a rough-type mutant (J5) E. coli-derived LPS component of a vaccine candidate. First, ion mobility filtered precursor ions were subjected to collision induced dissociation (CID) to define differences in native J5 LPS v. chemically detoxified J5 LPS (dLPS). Next, ultra-high mass resolving power, accurate mass spectrometry was employed for unequivocal precursor and product ion empirical formulae generation. Finally, MS3 analyses in an ion trap instrument showed that previous knowledge about dissociation of LPS components can be used to reconstruct and sequence LPS in a top down fashion. A structural rationale is also explained for differential inflammatory dose-response curves, in vitro, when HEK-Blue hTLR4 cells were administered increasing concentrations of native J5 LPS v. dLPS, which will be useful in future drug discovery efforts.n Graphical Abstractᅟ

Correction to: Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate

In the preceding article “Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate” by Oyler et al., an error in the J5 E. coli LPS chemical structure (Figs.xa02 and 4) was introduced and propagated into the final revision.

Septicemia and Chronic Hemodialysis

Excerpt To the editor: In their article, Septicemia in Patients on Chronic Hemodialysis (Ann Intern Med88:28-33, 1978), Dobkin, Miller, and Steigbigel take issue with our recommendation that acc...