Search

Abstract Gastroesophageal reflux disorder (GERD), a common disorder in the Western world, can lead to complications that include esophageal stricture and esophageal adenocarcinoma. Multiple challenges are associated with GERD treatment. [...]

Nasopharyngeal (NP) carriage is necessary for Streptococcus pneumoniae (Spn) transmission and invasive infection. This study evaluated the effect of zinc prophylaxis on the association between NP colonization with Spn and acute lower respiratory infection (ALRI) in children aged 1-35 mo living in a rural district in southern Nepal. We compared carriage prevalence of Spn in 550 ALRI cases with that of healthy age- and season-matched controls. This study, conducted from December 2003 to July 2005, was nested in a community-randomized trial designed to evaluate the effect of zinc on morbidity and mortality in 1- to 36-mo-old children. They were randomized to receive either 10-mg tablets of zinc or placebo daily until discharge. Approximately 75% of cases and controls were Spn carriers. There was an interaction between zinc and Spn carriage (P = 0.091). Spn carriage increased the risk of ALRI in the placebo group [adjusted matched odds ratio (AMOR) = 2.57; P = 0.025] but not in the zinc group (AMOR = 0.95; P = 0.890). Among the subset of symptomatic cases and their controls, the odds of ALRI for Spn carriers in the placebo group was 30 times greater (AMOR = 78.09; P= 0.006) than in the zinc group (AMOR = 2.77; P = 0.288). These findings suggest that zinc prophylaxis may protect children against ALRI associated with carriage of Spn and that the effect may differ by infectious etiology.

SET domain genes have been identified in numbers of bacterial genomes based on similarity to SET domains of eukaryotic histone methyltransferases. Herein, a Chlamydophila pneumoniae SET domain gene was clarified to be coincidently expressed with hctA and hctB genes encoding chlamydial histone H1-like proteins, Hc1 and Hc2, respectively. The SET domain protein (cpnSET) is localized in chlamydial cells and interacts with Hc1 and Hc2 through the C-terminal SET domain. As expected from conservation of catalytic sites in cpnSET, it functions as a protein methyltransferase to murine histone H3 and Hc1. However, little is known about protein methylation in the molecular pathogenesis of chlamydial infection, cpnSET may play an important role in chlamydial cell maturation due to modification of chlamydial histone H1-like proteins.

Abstract This article compares vancomycin, teicoplanin, quinupristin-dalfopristin, linezolid, daptomycin, tigecyline, dalbavancin, telavancin, ceftobiprole, oritavancin, and ramoplanin for the treatment of complicated skin and skin structure infections (cSSSI), methicillin-resistant Staphylococcus aureus [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2006.01.046 Byline: Young-Sun Kang (1), Yoonkyung Do (1), Hae-Kyung Lee (1), Sung Ho Park (1), Cheolho Cheong (1), Rebecca M. Lynch (1), Jutta M. Loeffler (2), Ralph M. Steinman (1), Chae Gyu Park (1) Abstract: The intricate system of serum complement proteins provides resistance to infection. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial binding C3 fragments recognized by leukocytes. The spleen and C3 provide resistance against blood-borne S. pneumoniae infection. To better understand the mechanisms involved, we studied SIGN-R1, a lectin that captures microbial polysaccharides in spleen. Surprisingly, conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-R1.sup.+ spleen macrophages, and formation of C3 ligands. We found that SIGN-R1 directly bound the complement C1 subcomponent, C1q, and assembled a C3 convertase, but without the traditional requirement for either antibody or factor B. The transmembrane lectin SIGN-R1 therefore contributes to innate resistance by an unusual C3 activation pathway. Author Affiliation: (1) Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA (2) Laboratory of Bacterial Pathogenesis, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA Article History: Received 11 October 2005; Revised 26 December 2005; Accepted 17 January 2006 Article Note: (miscellaneous) Published: April 6, 2006

We characterized the role of catabolite control protein A (ccpA) in the physiology and virulence of Streptococcus pneumoniae. S. pneumoniae has a large percentage of its genome devoted to sugar uptake and metabolism, and therefore, regulation of these processes is likely to be crucial for fitness in the nasopharynx and may play a role during invasive disease. In many bacteria, carbon catabolite repression (CCR) is central to such regulation, influencing hierarchical sugar utilization and growth rates. CcpA is the major transcriptional regulator in CCR in several gram-positive bacteria. We show that CcpA functions in CCR of lactose-inducible [beta]-galactosidase activity in S. pneumoniae. CCR of maltose-inducible [alpha]-glucosidase, raffinose-inducible [alpha]-galactosidase, and cellobiose-inducible [beta]-glucosidase is unaffected in the ccpA strain, suggesting that other regulators, possibly redundant with CcpA, control these systems. The ccpA strain is severely attenuated for nasopharyngeal colonization and lung infection in the mouse, establishing its role in fitness on these mucosal surfaces. Comparison of the cell wall fraction of the ccpA and wild-type strains shows that CcpA regulates many proteins in this compartment that are involved in central and intermediary metabolism, a subset of which are required for survival and multiplication in vivo. Both in vitro and in vivo defects were complemented by providing ccpA in trans. Our results demonstrate that CcpA, though not a global regulator of CCR in S. pneumoniae, is required for colonization of the nasopharynx and survival and multiplication in the lung.

The VicRK (YycFG) two-component regulatory, system (TCS) is required for virulence of the human respiratory pathogen Streptococcus pneumoniae (pneumococcus). The VicR (YycF) response regulator (RR) is essential through its positive regulation of pcsB, which encodes an extracellular protein that mediates murein biosynthesis. To determine other genes that are regulated by VicR, we performed microarray analyses on a unique [DELTA]vicR deletion mutant, which was constructed by uncoupling regulation of pcsB. Results from these microarray experiments support the idea that the VicR RR exerts strong positive regulation on the transcription of a set of genes encoding important surface proteins, including the PspA virulence factor, two proteins (Spr0096 and Spr1875) containing LysM peptidoglycan-binding domains, and a putative membrane protein (Spr0709) of unknown function. To demonstrate direct regulation, we performed band shift and footprinting experiments using purified unphosphorylated VicR and phosphorylated VicR-P, which was prepared by reaction with acetyl phosphate. VicR and VicR-P bound to regions upstream of pcsB, pspA, spr0096, spr1875, and spr0709. Phosphorylation of VicR to VicR-P increased the apparent strength and changed the nature of binding to these regions. DNase I footprinting of VicR and VicR-P bound to regions upstream of pcsB, pspA, spr0096, and spr1875 showed protection of extended regions containing a degenerate sequence related to a previously proposed consensus. These combined approaches did not support autoregulation of the vicRKX operon or substantive direct regulation of fatty acid biosynthesis by VicR or VicR-P. However, the [DELTA]vicR mutant required fatty acids in some conditions, which supports the notion that the VicRK TCS may mediate membrane integrity as well as murein biosynthesis and virulence factor expression in S. pneumoniae.

The Streptococcus pneumoniae LytC lysozyme is responsible for autolysis at 30[degrees]C (a temperature close to that of the upper respiratory tract), promotes DNA release in competent cultures, and participates in nasopharyngeal colonization. We show that the virulent pneumococcal TIGR4 strain encodes an active LytC enzyme, in contrast with genome-based predictions.

The YycFG two-component system, originally identified in Bacillus subtilis, is highly conserved among gram-positive bacteria with low G+C contents. In Streptococcus pneumoniae, the YycF response regulator has been reported to be essential for cell growth, but the signal to which it responds and the gene members of the regulon remain unclear. In order to investigate the role of YycFG in S. pneumoniae, we increased the expression of yycF by using a maltose-inducible vector and analyzed the genome-wide effects on transcription and protein expression during the course of yycF expression. The induction of yycF expression increased histidine kinase yycG transcript levels, suggesting an autoregulation of the yycFG operon. Evidence from both proteomic and microarray transcriptome studies as well as analyses of membrane fatty acid composition indicated that YycFG is involved in the regulation of fatty acid biosynthesis pathways and in determining fatty acid chain lengths in membrane lipids. In agreement with recent transcriptome data on pneumococcal cells depleted of YycFG, we also identified several other potential members of the YycFG regulon that are required for virulence and cell wall biosynthesis and metabolism.

Byline: T. Varpula (1), V. Pettila (1), E. Rintala (2), O. Takkunen (1), V. Valtonen (3) Keywords: Key words ALI; ARDS; Pneumococcal pneumonia; Corticosteroids; Methylprednisolone; Fibroproliferation Abstract: Objective: To investigate the effect of steroid treatment in the late phase of primary acute lung injury (ALI) with special emphasis on pneumococcal pneumonia. Design: Retrospective study. Setting: Multidisciplinary intensive care unit (ICU) in a university hospital. Patients: Of 31 patients with primary ALI requiring mechanical ventilation for more than 10 days, 16 were treated with methylprednisolone and 15 served as controls. Measurements and results: Steroid and control groups were comparable regarding demographic data, APACHE II score, Multiple Organ Dysfunction Score (MODS), and PaO.sub.2/FiO.sub.2-ratio on admission to ICU. The mean start of steroid therapy was 9.7 days after establishment of respiratory failure, and values for control patients were registered on day 10. The PaO.sub.2/FiO.sub.2 ratio improved significantly within 3 days after the start of steroid therapy, and MODS and C-reactive protein decreased concurrently. No differences in mortality, in length of ICU stay, or in length of mechanical ventilation were detectable. In a subgroup analysis, for patients with Streptococcus pneumoniae pneumonia, beneficial change in physiological variables was evident. Conclusions: In patients with primary ALI, steroid therapy, started 10 days after the start of mechanical ventilation, improves gas exchange and is associated with a decrease in multiorgan dysfunction. Author Affiliation: (1) Intensive Care Unit, Department of Anesthesiology, Division of Surgery, Helsinki University Central Hospital, Haartmaninkatu 4, 00290 Helsinki, Finland e-mail: tero.varpula@huch.fi Tel.: + 3 58-9-47 11 Fax: + 3 58-9-47 17 56 78, FI (2) Department of Internal Medicine, Satakunta Central Hospital, Pori, Finland, FI (3) Division of Infectious Diseases, Department of Internal Medicine, Helsinki University Central Hospital, Finland , FI Article note: Received: 21 July 1999 Final revision received: 1 November 1999 Accepted: 15 December 1999

Byline: J. Braun (1), M. Pein (1), H. Djonlagic (1), K. Dalhoff (1) Keywords: Key words Pneumonia; Central venous neutrophils; Reactive oxygen species; Chemiluminescence; Elastase; [alpha]1-proteinase inhibitor; [alpha]2-proteinase inhibitor Abstract: Objective: In pneumonia the influx of neutrophils to the lungs is thought to be of primary importance with regard to host defence and to complications like the adult respiratory distress syndrome. We wanted to evaluate the neutrophil function in patients in acute respiratory failure who required admission to the intensive care unit. Design: We determined the luminol-enhanced chemiluminescence (CL) of neutrophils isolated both from central venous and arterial blood. In addition, the plasma-concentrations of [alpha].sub.1-proteinase inhibitor, ([alph[a].sub.1]PI), [alpha].sub.2-macroglobulin ([alph[a].sub.2]PI) and elastase-[alph[a].sub.1]PI-complex (elastase) were determined by chemiluminescence immunoassay, and the intracellular elastase content of blood neutrophils was determined using immuno activation assay. Patients: 28 Patients, 18 with acute pneumonia (group 1) and 10 with cardiac pulmonary edema (group 2). Measurements and results: In group 1, luminol enhanced CL was significantly higher than in group 2 (mean 87.7 vs 30.4x10.sup.6 counts per minute, p&lt 0.01). The production of reactive oxygen species was significantly higher in central venous than in arterial neutrophils in the patients with pneumonia (p&lt 0.03). In patients with pulmonary edema there was no such difference. The plasma concentration of elastase in group 1 was significantly higher than in group 2, that of [alph[a].sub.2]PI were significantly lower. The intracellular elastase content of neutrophils was lower in group 1 than in group 2. In group 1, there was a trend for a correlation between lower intracellular elastase content and a higher elastase plasma concentration. There were no central venous -- arterial differences with regard to leukocyte count, cell differential or protein concentration in either group. Conclusion: The central venous -- arterial differences in neutrophil production of reactive oxygen species support the concept of compartmentalization of activated neutrophils from the systemic to the pulmonary compartment. Author Affiliation: (1) Department of Medicine II, Medical University of Lubeck, Ratzeburger Allee 160, D-23538 Lubeck, Germany FAX: +49 (451) 5002938, DE Article note: Received: 15 June 1995 Accepted: 18 September 1996

Summary Bacterial infections of the respiratory tract are a major cause of morbidity and mortality in elderly people. The inflammatory response to such infection is an important protective process and [...]