Nitric oxide-dependent killing of aerobic, anaerobic and persistent Burkholderia pseudomallei

Jones-Carson, Jessica; Laughlin, James R.; Stewart, Amanda L.; Voskuil, Martin I.; Vázquez‐Torres, Andrés

doi:10.1016/j.niox.2012.04.001

Cited by 30 publications

(23 citation statements)

References 50 publications

(69 reference statements)

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“…In addition, NO is bacteriostatic for several organisms, including Escherichia coli, 28 and bactericidal for some. 29 It may be that alteration in bowel flora by hydroxyurea somehow reduced the incidence of gastroenteritis.…”

Section: Discussionmentioning

confidence: 99%

Impact of hydroxyurea on clinical events in the BABY HUG trial

Thornburg

Files

Luo

et al. 2012

Blood

226

185

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The Pediatric Hydroxyurea Phase 3 Clinical Trial (BABY HUG) was a phase 3 multicenter, randomized, double-blind, placebocontrolled clinical trial of hydroxyurea in infants (beginning at 9-18 months of age) with sickle cell anemia. An important secondary objective of this study was to compare clinical events between the hydroxyurea and placebo groups. One hundred and ninetythree subjects were randomized to hy- Continuing Medical Education onlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and the American Society of Hematology. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™ . Physicians should claim only the credit commensurate with the extent of their participationin the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http://www.medscape.org/journal/blood; and (4) view/print certificate. For CME questions, see page 4448. Disclosures The authors, the Associate Editor Narla Mohandas, and CME questions author Laurie Barclay, freelance writer and reviewer, Medscape, LLC, declare no competing financial interests. Learning objectivesUpon completion of this activity, participants will be able to:1. Describe the effect of hydroxyurea on rates of sickle cell complications for infants with sickle cell anemia (SCA) on the basis of a phase 3, multicenter, randomized trial.2. Describe the effect of hydroxyurea on rates of hospitalizations and transfusions for infants with SCA on the basis of a phase 3, multicenter, randomized trial.3. Describe the safety of hydroxyurea for infants with SCA on the basis of a phase 3, multicenter, randomized trial.

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Section: Discussionmentioning

confidence: 99%

Impact of hydroxyurea on clinical events in the BABY HUG trial

Thornburg

Files

Luo

et al. 2012

Blood

226

185

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“…pseudomallei is mediated to a large extent by reactive nitrogen species and to a lesser extent by reactive oxygen species (ROS) [24], [25]. PGE 2 has been shown to suppress nitric oxide (NO) synthesis in Kupffer cells, hepatocytes, murine peritoneal macrophages, and RAW 264.7 murine macrophages [26].…”

Section: Resultsmentioning

confidence: 99%

Post-Exposure Therapeutic Efficacy of COX-2 Inhibition against Burkholderia pseudomallei

et al. 2013

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Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. In this work, we demonstrate that host prostaglandin E2 (PGE2) production plays a regulatory role in the pathogenesis of B. pseudomallei. PGE2 promotes B. pseudomallei intracellular survival within macrophages and bacterial virulence in a mouse model of pneumonic melioidosis. PGE2-mediated immunosuppression of macrophage bactericidal effector functions is associated with increased arginase 2 (Arg2) expression and decreased nitric oxide (NO) production. Treatment with a commercially-available COX-2 inhibitor suppresses the growth of B. pseudomallei in macrophages and affords significant protection against rapidly lethal pneumonic melioidosis when administered post-exposure to B. pseudomallei-infected mice. COX-2 inhibition may represent a novel immunotherapeutic strategy to control infection with B. pseudomallei and other intracellular pathogens.

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“…Also more abundant were proteins involved in fatty acid synthesis, enoyl coenzyme A hydratase, Dtpsy_2933 (P ϭ 0.11), and a member of the 2-nitropropane dioxygenase family, Dtpsy_2296 (P ϭ 0.055), that is closely related to a Neisseria gonorrhoeae homolog (NGO1024) putatively involved in anaerobic, NO-dependent fatty acid synthesis (44). Aconitase, Dtpsy_1066 (P ϭ 0.25), which is sensitive to nitrosative stress (45), and the large subunit of NO reductase, Dtpsy_0109 (P ϭ 0.13) (46), were also observed more often in Fe(II) cultures, but the P values are higher (see Data Set S1). Two proteins, Dtpsy_0452 (P ϭ 0.030) and Dtpsy_1098 (P ϭ 0.045), were significantly less abundant in NDFO cultures of A. ebreus (see Data Set S1).…”

Section: Evidence Against An Inducible Fe(ii) Oxidoreductase Inmentioning

confidence: 99%

Fe(II) Oxidation Is an Innate Capability of Nitrate-Reducing Bacteria That Involves Abiotic and Biotic Reactions

Carlson

Clark²,

Blazewicz³

et al. 2013

Journal of Bacteriology

153

160

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Phylogenetically diverse species of bacteria can catalyze the oxidation of ferrous iron [Fe(II)] coupled to nitrate (NO 3؊ ) reduction, often referred to as nitrate-dependent iron oxidation (NDFO). Very little is known about the biochemistry of NDFO, and though growth benefits have been observed, mineral encrustations and nitrite accumulation likely limit growth. Acidovorax ebreus, like other species in the Acidovorax genus, is proficient at catalyzing NDFO. Our results suggest that the induction of specific Fe(II) oxidoreductase proteins is not required for NDFO. No upregulated periplasmic or outer membrane redox-active proteins, like those involved in Fe(II) oxidation by acidophilic iron oxidizers or anaerobic photoferrotrophs, were observed in proteomic experiments. We demonstrate that while "abiotic" extracellular reactions between Fe(II) and biogenic NO 2 ؊ /NO can be involved in NDFO, intracellular reactions between Fe(II) and periplasmic components are essential to initiate extensive NDFO. We present evidence that an organic cosubstrate inhibits NDFO, likely by keeping periplasmic enzymes in their reduced state, stimulating metal efflux pumping, or both, and that growth during NDFO relies on the capacity of a nitrate-reducing bacterium to overcome the toxicity of Fe(II) and reactive nitrogen species. On the basis of our data and evidence in the literature, we postulate that all respiratory nitrate-reducing bacteria are innately capable of catalyzing NDFO. Our findings have implications for a mechanistic understanding of NDFO, the biogeochemical controls on anaerobic Fe(II) oxidation, and the production of NO 2 ؊ , NO, and N 2 O in the environment.

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Nitric oxide-dependent killing of aerobic, anaerobic and persistent Burkholderia pseudomallei

Cited by 30 publications

References 50 publications

Impact of hydroxyurea on clinical events in the BABY HUG trial

Impact of hydroxyurea on clinical events in the BABY HUG trial

Post-Exposure Therapeutic Efficacy of COX-2 Inhibition against Burkholderia pseudomallei

Fe(II) Oxidation Is an Innate Capability of Nitrate-Reducing Bacteria That Involves Abiotic and Biotic Reactions

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