The Brief Case: Recurrent Chromobacterium violaceum Bloodstream Infection in a Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Patient with a Severe Neutrophil Defect.
Ontology highlight
ABSTRACT:
SUBMITTER: Thwe PM
PROVIDER: S-EPMC6989066 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Publications
The Brief Case: Recurrent Chromobacterium violaceum Bloodstream Infection in a Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Patient with a Severe Neutrophil Defect.
Thwe Phyu M PM Ortiz Daniel A DA Wankewicz Alyssa L AL Hornak J Patrik JP Williams-Bouyer Natalie N Ren Ping P
Journal of clinical microbiology 20200128 2
Similar Datasets
Project description:Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway and provides reducing energy to all cells by maintaining redox balance. The most common clinical manifestations in patients with G6PD deficiency are neonatal jaundice and acute hemolytic anemia. The effects of microbial infection in patients with G6PD deficiency primarily relate to the hemolytic anemia caused by Plasmodium or viral infections and the subsequent medication that is required. We are interested in studying the impact of bacterial infection in G6PD-deficient cells. G6PD knock down A549 lung carcinoma cells, together with the common pathogen Staphylococcus aureus, were employed in our cell infection model. Here, we demonstrate that a lower cell viability was observed among G6PD-deficient cells when compared to scramble controls upon bacterial infection using the MTT assay. A significant increase in the intracellular ROS was detected among S. aureus-infected G6PD-deficient cells by observing dichlorofluorescein (DCF) intensity within cells under a fluorescence microscope and quantifying this signal using flow cytometry. The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. A higher expression level of the intrinsic apoptotic initiator caspase-9, as well as the downstream effector caspase-3, was detected by Western blotting analysis of G6PD-deficient cells following bacterial infection. In conclusion, we propose that bacterial infection, perhaps the secreted S. aureus ?-hemolysin in this case, promotes the accumulation of intracellular ROS in G6PD-deficient cells. This would trigger a stronger apoptotic activity through the intrinsic pathway thereby reducing cell viability when compared to wild type cells.
| S-EPMC3817128 | biostudies-literature
Project description:Disturbances in the count or maturity of blood cells weaken their microbial defensive capacity and render them more susceptible to infections. Glucose-6-phosphate deficient patients are affected by a genetic disease that affects cell integrity with increased liability to infections and death. We aimed to investigate the risk factors for infection mortality in this patient population. We retrospectively examined the records of G6PD adult patients with confirmed infections and collected data related to demographics, infections (pathogens, types, and treatment regimens) in addition to mortality and length of stay outcomes. Data were statistically analyzed using R Programming language to identify contributing factors to mortality and treatment regimens association with outcomes. Records of 202 unique patients over 5 years were included, corresponding to 379 microbiologically and clinically confirmed infections. Patients > 60 years [p = 0.001, OR: 5.6], number of comorbidities 4 (2-5) [p < 0.001, OR: 1.8], patients needed blood transfusion [p = 0.003, OR: 4.3]. Respiratory tract infections [p = 0.037, OR: 2.28], HAIs [p = 0.002, OR: 3.9], polymicrobial infections [p = 0.001, OR: 10.9], and concurrent infection Gram-negative [p < 0.001, OR: 7.1] were significant contributors to 28-day mortality. The history of exposure to many antimicrobial classes contributed significantly to deaths, including β-lactam/β-lactamase [p = 0.002, OR: 2.5], macrolides [p = 0.001, OR: 3.34], and β-lactams [p = 0.012, OR: 2.0]. G6PD patients are a unique population that is more vulnerable to infections. Prompt and appropriate antimicrobial therapy is warranted to combat infections. A strict application of stewardship principles (disinfection, shortening the length of stay, and controlling comorbid conditions) may be beneficial for this population. Finally, awareness of the special needs of this patient group may improve treatment outcomes.
| S-EPMC10044656 | biostudies-literature
Project description:Here, we described a novel transcriptional regulator belonging to the MarR family that we named OsbR (oxidative stress response and biofilm formation regulator) in the opportunistic pathogen Chromobacterium violaceum. Transcriptome profiling by DNA microarray using strains with deletion or overexpression of osbR showed that OsbR exert a global regulatory role in C. violaceum, regulating genes involved in oxidative stress response, nitrate reduction, biofilm formation, and several metabolic pathways. EMSA assays showed that OsbR binds to the promoter regions of several OsbR-regulated genes and the in vitro DNA binding activity was inhibited by oxidants. We demonstrated that the overexpression of osbR caused activation of ohrA even in the presence of the repressor OhrR, which resulted in improved growth under organic hydroperoxide treatment. We showed that the proper regulation of the nar genes by OsbR ensures an optimal growth of C. violaceum under anaerobic conditions by tuning the reduction of nitrate to nitrite. Finally, the osbR overexpressing strain showed reduction in biofilm formation and this phenotype correlated with the OsbR-mediated repression of two gene clusters encoding putative adhesins.
2021-04-11 | GSE171860 | GEO
Project description:Antibiotic resistance can arise by several mechanisms, including mutation in transcription factors that regulate drug efflux pumps. In this work, we identified EmrR as a MarR family transcription factor involved in antibiotic resistance in Chromobacterium violaceum, a Gram-negative bacterium that occurs in soil and water and can act as a human opportunistic pathogen. Antibiogram and minimum inhibitory concentration (MIC) assays showed that the ΔemrR mutant presented increased resistance to the antibiotic nalidixic acid in respect to the wild-type strain. The emrR gene is near to a putative operon emrCAB, which encode the efflux pump EmrCAB. DNA Microarray analysis showed that EmrR represses the emrCAB operon and some other putative transporters. Northern blot assays validated that EmrR represses the emrCAB operon and this repression can be released by salicylate, but not other compounds such as nalidixic acid or ethidium bromide. Electrophoretic mobility shift assays (EMSA) showed that EmrR binds directly to the promoter regions of emrR, emrCAB and other genes to exert negative regulation. Therefore, in response to compounds as salicylate, EmrR derepresses the operon emrCAB causing overexpression of the efflux pump EmrCAB and increased resistance to nalidixic acid in C. violaceum.
2018-11-01 | GSE112521 | GEO
Project description:Chromobacterium violaceum is an abundant component of the soil and water microbiota in tropical and subtropical regions around the world. For many years, it was mainly known as a producer of violacein and as a reporter for the discovery of quorum sensing molecules. However, C. violaceum has recently emerged as an important model of an environmental opportunistic pathogen. Its high virulence in human infections and a mouse infection model involves the possession of several predicted virulence traits, including two type III secretion systems (T3SSs). In this article, in addition to providing an update on the new clinical cases of human C. violaceum infections, we will focus on recent advances in understanding the molecular mechanisms regarding C. violaceum pathogenesis. It has been demonstrated that the C. violaceum Cpi-1 T3SS plays a pivotal role in interaction with host cells. It is required for the secretion of effector proteins and is the agonist recognized by the Nod-like receptor CARD domain-containing protein 4 (NLRC4) inflammasome from innate immune cells. Pyroptosis and its release of hepatocytes for killing by neutrophils are key events required for the clearance of C. violaceum. Given the prominent role of T3SSs in C. violaceum virulence, we examine their occurrence in the Chromobacterium genus, taking advantage of several draft genome sequences of Chromobacterium species that have recently become available. Our finding that the Cpi-1 T3SS is widespread among Chromobacterium species points toward the pathogenic potential of this genus for humans or to novel roles of the T3SS in the interaction of Chromobacterium species with other organisms.
| S-EPMC5686120 | biostudies-literature
Project description:We announce the draft genome sequence for Chromobacterium violaceum strain CV017, used as a model and tool to understand acyl-homoserine lactone-dependent quorum sensing. The assembly consists of 4,774,638-bp contained in 211 scaffolds.
| S-EPMC4777762 | biostudies-literature
Project description:In this study, we used transcriptional profiling to define the adaptive response of C. violaceum to oxidative stress induced by cumene hydroperoxide (CHP) and to identify the OhrR regulon. DNA microarray and northern blot analysis revealed that in CHP-treated cells occur strong upregulation of genes involved in many pathways for stress protection, including antioxidant enzymes (catalase and peroxidases), thioredoxin, glutaredoxin and lipoyl-dependent reducing systems, DNA repair enzymes, heat shock response (σ32 regulon), iron limitation (Fur regulon) and nitrogen starvation. Genes encoding glyoxalases, glutathione S-transferases and oxygenases were also induced, suggesting further catabolism of the aromatic compound CHP. Pathways downregulated by CHP stress include electron transport chain, nucleotide biosynthesis and unsaturation of fatty acids. Further, we identified two upregulated genes (OhrA and a protein with GGDEF domain for c-di-GMP synthesis) and three downregulated genes (hemolysin, chitinase and collagenase) in the ohrR mutant. Using a mouse infection model, we demonstrate that the ohrR mutant, but not the ohrA mutant, is attenuated for virulence and showed a decreased bacterial burden in the liver. Therefore, we have defined the CHP stimulon and determined that C. violaceum uses the organic hydroperoxide sensor OhrR for regulate expression of genes required to antioxidant defense and to modulate virulence in its interaction with the host.
2017-05-01 | GSE90551 | GEO
Project description:The genus Chromobacterium is widely distributed in the environment and is composed of Gram-negative, aerobic, or facultative anaerobic bacilli that occur in violet-colored colonies. These bacteria rarely cause infections, but when it occurs, it spreads quickly and has a high mortality. Because diseases are infrequent, the diagnosis is often delayed, and it takes time for suitable treatment to be initiated, leading to increased mortality due to the rapid progression of the disease. After the death of a cougar, serologically positive for feline leukemia virus, at the Center for Medicine and Research on Wild Animals of the Federal University of Mato Grosso, an autopsy was carried out, and fragments of its organs were sent for bacterial culture. Significant lesions were found, mainly in the liver and lungs, and upon bacterial isolation, violet-colored colonies were obtained from all of the referred organs, suggestive of C. violaceum, which was later confirmed by 16S DNA sequencing. The objective of this study was to report a case of death associated primarily with disseminated infection caused by C. violaceum in a FeLV-positive wild cougar in July 2018; no other occurrence in this species has yet been described.
| S-EPMC8324757 | biostudies-literature
Project description:Quorum sensing (QS) is a communication system used by bacteria to coordinate a wide panel of biological functions in a cell density-dependent manner. The Gram-negative Chromobacterium violaceum has previously been shown to use an acyl-homoserine lactone (AHL)-based QS to regulate various behaviors, including the production of proteases, hydrogen cyanide, or antimicrobial compounds such as violacein. By using combined metabolomic and proteomic approaches, we demonstrated that QS modulates the production of antimicrobial and toxic compounds in C. violaceum ATCC 12472. We provided the first evidence of anisomycin antibiotic production by this strain as well as evidence of its regulation by QS and identified new AHLs produced by C. violaceum ATCC 12472. Furthermore, we demonstrated that targeting AHLs with lactonase leads to major QS disruption yielding significant molecular and phenotypic changes. These modifications resulted in drastic changes in social interactions between C. violaceum and a Gram-positive bacterium (Bacillus cereus), a yeast (Saccharomyces cerevisiae), immune cells (murine macrophages), and an animal model (planarian Schmidtea mediterranea). These results underscored that AHL-based QS plays a key role in the capacity of C. violaceum to interact with micro- and macroorganisms and that quorum quenching can affect microbial population dynamics beyond AHL-producing bacteria and Gram-negative bacteria.
| S-EPMC8062528 | biostudies-literature
Project description:The precipitous drop in the cost of genomic sequencing and the concomitant availability of computational methods for comparing genome-level data has made the accurate taxonomic placement of bacteria affordable and relatively rapid. Inaccurate taxonomic placement of bacteria has serious implications in clinical, environmental, and regulatory microbiology, but it can also adversely affect interpretation of research results. The quorum biosensor strain CV026 was derived from an isolate of Chromobacterium that was labeled as C. violaceum ATCC 31532, and is catalogued by the ATCC under that species name. Nearly 200 papers have been published that use CV026 as an indicator for quorum sensing activity in many Gram negative bacteria, but the inability of C. violaceum strains to complement the quorum sensing mutation in CV026 has called the taxonomic placement of the parent strain into question. We used molecular phylogeny and a large number of metabolic and phenotypic characters to demonstrate that Chromobacterium strain ATCC 31532 is a member of species Chromobacterium subtsugae.
| S-EPMC7648793 | biostudies-literature