Phagocyte NADPH Oxidase, but Not Inducible Nitric Oxide Synthase, Is Essential for Early Control of
            <i>Burkholderia cepacia</i>
            and
            <i>Chromobacterium violaceum</i>
            Infection in Mice

Segal, Brahm H.; Ding, Li; Holland, Steven M.

doi:10.1128/iai.71.1.205-210.2003

Cited by 33 publications

(30 citation statements)

References 37 publications

(35 reference statements)

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“…C. violaceum infection in CGD patients is typified by rapid bacteremia often without a nidus of infection, and a 53% mortality rate (Yang and Li, 2011). This is experimentally demonstrated in mice, where C. violaceum has minimal virulence for WT C57BL/6 mice, while it is highly virulent in Ncf1 −/− mice (Segal et al, 2003) (Figure 1E). We found that like Ncf1 −/− mice, Casp1 −/− Casp11 −/− mice were acutely susceptible to C. violaceum infection.…”

Section: Resultsmentioning

confidence: 69%

Inflammasomes Coordinate Pyroptosis and Natural Killer Cell Cytotoxicity to Clear Infection by a Ubiquitous Environmental Bacterium

et al. 2015

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SUMMARY Defective neutrophils in patients with chronic granulomatous disease (CGD) cause susceptibility to extracellular and intracellular infections. As microbes must first be ejected from intracellular niches to expose them to neutrophil attack, we hypothesized that inflammasomes detect certain CGD pathogens upstream of neutrophil killing. Here, we identified one such ubiquitous environmental bacterium, Chromobacterium violaceum, whose extreme virulence was fully counteracted by the NLRC4 inflammasome. Caspase-1 protected via two parallel pathways that eliminated intracellular replication niches. Pyroptosis was the primary bacterial clearance mechanism in the spleen, but both pyroptosis and interleukin-18 (IL-18)-driven natural killer (NK) cell responses were required for liver defense. NK cells cleared hepatocyte replication niches via perforin-dependent cytotoxicity, whereas interferon-γ was not required. These insights suggested a therapeutic approach; exogenous IL-18 restored perforin-dependent cytotoxicity during infection by the inflammasome-evasive bacterium Listeria monocytogenes. Therefore, inflammasomes can trigger complementary programmed cell death mechanisms, directing sterilizing immunity against intracellular bacterial pathogens.

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Section: Resultsmentioning

confidence: 69%

Inflammasomes Coordinate Pyroptosis and Natural Killer Cell Cytotoxicity to Clear Infection by a Ubiquitous Environmental Bacterium

et al. 2015

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“…The clearance of C. violaceum infection is mediated by the NLRC4 inflammasome that triggers pyroptosis in macrophages or natural killer cytotoxicity in liver cells to expose C. violaceum to neutrophil killing (29). NADPH oxidase-deficient mice or patients with chronic granulomatous disease (CGD) are highly susceptible to C. violaceum infection (25,29,30), indicating the pivotal role of ROS derived from phagocytes in the control of C. violaceum.…”

mentioning

confidence: 99%

Global Transcriptional Response to Organic Hydroperoxide and the Role of OhrR in the Control of Virulence Traits in Chromobacterium violaceum

et al. 2017

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A major pathway for the detoxification of organic hydroperoxides, such as cumene hydroperoxide (CHP), involves the MarR family transcriptional regulator OhrR and the peroxidase OhrA. However, the effect of these peroxides on the global transcriptome and the contribution of the OhrA/OhrR system to bacterial virulence remain poorly explored. Here, we analyzed the transcriptome profiles of Chromobacterium violaceum exposed to CHP and after the deletion of ohrR, and we show that OhrR controls the virulence of this human opportunistic pathogen. DNA microarray and Northern blot analyses of CHP-treated cells revealed the upregulation of genes related to the detoxification of peroxides (antioxidant enzymes and thiol-reducing systems), the degradation of the aromatic moiety of CHP (oxygenases), and protection against other secondary stresses (DNA repair, heat shock, iron limitation, and nitrogen starvation responses). Furthermore, we identified two upregulated genes (ohrA and a putative diguanylate cyclase with a GGDEF domain for cyclic di-GMP [c-di-GMP] synthesis) and three downregulated genes (hemolysin, chitinase, and collagenase) in the ohrR mutant by transcriptome analysis. Importantly, we show that OhrR directly repressed the expression of the putative diguanylate cyclase. Using a mouse infection model, we demonstrate that the ohrR mutant was attenuated for virulence and showed a decreased bacterial burden in the liver. Moreover, an ohrRdiguanylate cyclase double mutant displayed the same virulence as the wild-type strain. In conclusion, we have defined the transcriptional response to CHP, identified potential virulence factors such as diguanylate cyclase as members of the OhrR regulon, and shown that C. violaceum uses the transcriptional regulator OhrR to modulate its virulence.KEYWORDS oxidative stress, organic hydroperoxides, CHP stimulon, OhrA/OhrR system, MarR family, bacterial virulence, cumene hydroperoxide, diguanylate cyclase, transcription factors B acteria are exposed to reactive oxygen species (ROS) generated endogenously or produced by phagocytic cells from the mammalian immune system (1-3). Other harmful oxidants are organic hydroperoxides (OHPs) produced either enzymatically during eicosanoid metabolism (4) or by the free radical-catalyzed oxidation of polyunsaturated fatty acids (PUFAs) during lipid peroxidation (5). In the lipid peroxidation process, multiple toxic breakdown molecules are generated, including lipid hydroperoxides (LHPs) and short-chain aldehydes such as malondialdehyde (MDA) (5, 6). Because bacterial membranes are usually devoid of PUFAs and contain mainly saturated fatty acids and monounsaturated fatty acids (UFAs) (7), lipid peroxidation in bacteria is

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“…Similarly to healthy people, normal mice are resistant to the Bcc and usually show only transient infections upon inoculation (8,37). On the other hand, CGD mice are highly susceptible to Bcc infection and show clinical signs that are similar to those of the human disease (20,31,37).…”

mentioning

confidence: 90%

“…The virulence of selected B. multivorans strains was evaluated in autosomal-recessive CGD (p47 phoxϪ/Ϫ ) C57BL/6 background mice (20). A total of 4 ϫ 10 5 CFU of strain CGD1 or Env1 were inoculated intraperitoneally into groups of six to eight mice, and the number of moribund or dead mice was recorded (37). Wild-type C57BL/6 mice (Taconic) were used as controls.…”

Section: Methodsmentioning

confidence: 99%

“…On the other hand, mouse models of CGD allow the direct study of Bcc virulence in a target disease (20,31). The Bcc is thought to be virulent in CGD due to its apparent intrinsic resistance to nonoxidative killing (37,40); wild-type mice are known to be resistant to the Bcc (12,20,26). We compared the in vivo virulence of a clinical isolate (CGD1) to that of an environmental strain (Env1) in a mouse model of FIG.…”

Section: Vol 77 2009 B Multivorans In Chronic Granulomatous Diseasmentioning

confidence: 99%

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Virulence and Cellular Interactions ofBurkholderia multivoransin Chronic Granulomatous Disease

Zelazny

Ding²,

Elloumi³

et al. 2009

Infect Immun

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Chronic granulomatous disease (CGD) patients are susceptible to life-threatening infections by the Burkholderia cepacia complex. We used leukocytes from CGD and healthy donors and compared cell association, invasion, and cytokine induction by Burkholderia multivorans strains. A CGD isolate, CGD1, showed higher cell association than that of an environmental isolate, Env1, which correlated with cell entry. All B. multivorans strains associated significantly more with cells from CGD patients than with those from healthy donors. Similar findings were observed with another CGD pathogen, Serratia marcescens, but not with Escherichia coli. In a mouse model of CGD, strain CGD1 was virulent while Env1 was avirulent. B. multivorans organisms were found in the spleens of CGD1-infected mice at levels that were 1,000 times higher than those found in Env1-infected mice, which was coincident with higher levels of the proinflammatory cytokine interleukin-1␤. Taken together, these results may shed light on the unique susceptibility of CGD patients to specific pathogens.

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Phagocyte NADPH Oxidase, but Not Inducible Nitric Oxide Synthase, Is Essential for Early Control of Burkholderia cepacia and Chromobacterium violaceum Infection in Mice

Cited by 33 publications

References 37 publications

Inflammasomes Coordinate Pyroptosis and Natural Killer Cell Cytotoxicity to Clear Infection by a Ubiquitous Environmental Bacterium

Inflammasomes Coordinate Pyroptosis and Natural Killer Cell Cytotoxicity to Clear Infection by a Ubiquitous Environmental Bacterium

Global Transcriptional Response to Organic Hydroperoxide and the Role of OhrR in the Control of Virulence Traits in Chromobacterium violaceum

Virulence and Cellular Interactions ofBurkholderia multivoransin Chronic Granulomatous Disease

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