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Nature Jun 2022Among the caspases that cause regulated cell death, a unique function for caspase-7 has remained elusive. Caspase-3 performs apoptosis, whereas caspase-7 is typically...
Among the caspases that cause regulated cell death, a unique function for caspase-7 has remained elusive. Caspase-3 performs apoptosis, whereas caspase-7 is typically considered an inefficient back-up. Caspase-1 activates gasdermin D pores to lyse the cell; however, caspase-1 also activates caspase-7 for unknown reasons. Caspases can also trigger cell-type-specific death responses; for example, caspase-1 causes the extrusion of intestinal epithelial cell (IECs) in response to infection with Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium). Here we show in both organoids and mice that caspase-7-deficient IECs do not complete extrusion. Mechanistically, caspase-7 counteracts gasdermin D pores and preserves cell integrity by cleaving and activating acid sphingomyelinase (ASM), which thereby generates copious amounts of ceramide to enable enhanced membrane repair. This provides time to complete the process of IEC extrusion. In parallel, we also show that caspase-7 and ASM cleavage are required to clear Chromobacterium violaceum and Listeria monocytogenes after perforin-pore-mediated attack by natural killer cells or cytotoxic T lymphocytes, which normally causes apoptosis in infected hepatocytes. Therefore, caspase-7 is not a conventional executioner but instead is a death facilitator that delays pore-driven lysis so that more-specialized processes, such as extrusion or apoptosis, can be completed before cell death. Cells must put their affairs in order before they die.
Topics: Animals; Apoptosis; Caspase 7; Chromobacterium; Epithelial Cells; Intestines; Killer Cells, Natural; Listeria monocytogenes; Mice; Organoids; Perforin; Phosphate-Binding Proteins; Pore Forming Cytotoxic Proteins; Sphingomyelin Phosphodiesterase; T-Lymphocytes, Cytotoxic
PubMed: 35705808
DOI: 10.1038/s41586-022-04825-8 -
Asian Pacific Journal of Tropical... Aug 2017Chromobacterium violaceum is a gram-negative bacterium, which has been used widely in microbiology labs involved in quorum sensing (QS) research. Among the QS-regulated... (Review)
Review
Chromobacterium violaceum is a gram-negative bacterium, which has been used widely in microbiology labs involved in quorum sensing (QS) research. Among the QS-regulated traits of this bacterium, violacein production has received the maximum attention. Violacein production in this organism, however is not under sole control of QS machinery, and other QS-regulated traits of this bacterium also need to be investigated in better detail. Though not often involved in human infections, this bacterium is being viewed as an emerging pathogen. This review attempts to highlight the recent research advances on C. violaceum, with respect to violacein biosynthesis, development of various applications of this bacterium and its bioactive metabolite violacein, and its pathogenicity.
PubMed: 28942822
DOI: 10.1016/j.apjtm.2017.07.022 -
Marine Drugs Jan 2022Quorum sensing (QS) can regulate the pathogenicity of bacteria and the production of some virulence factors. It is a promising target for screening to find...
Quorum sensing (QS) can regulate the pathogenicity of bacteria and the production of some virulence factors. It is a promising target for screening to find anti-virulence agents in the coming post-antibiotics era. Cyclo (-Trp--Ser), one variety of cyclic dipeptides (CDPs), isolated from a marine bacterium , exhibited anti-QS activity against CV026 and PAO1. Unlike the CDPs composed of phenylalanine or tyrosine, the anti-QS activity has been widely studied; however, cyclo (-Trp--Ser) and derivatives, containing one tryptophan unit and one non-aromatic amino acid, have not been systematically explored. Herein, the cyclo (-Trp--Ser) and seven derivatives were synthesized and evaluated. All tryptophane-contained CDPs were able to decrease the production of violacein in CV026 and predicted as binding within the same pocket of receptor protein CviR, but in lower binding energy compared with the natural ligand CHSL. As for PAO1, owning more complicated QS systems, these CDPs also exhibited inhibitory effects on pyocyanin production, swimming motility, biofilm formation, and adhesion. These investigations suggested a promising way to keep the tryptophan untouched and make modifications on the non-aromatic unit to increase the anti-QS activity and decrease the cytotoxicity, thus developing a novel CDP-based anti-virulence agent.
Topics: A549 Cells; Animals; Anti-Bacterial Agents; Biofilms; Chromatiaceae; Chromobacterium; Dipeptides; Humans; Mice; NIH 3T3 Cells; Pseudomonas aeruginosa; Quorum Sensing; Tryptophan; Virulence
PubMed: 35200615
DOI: 10.3390/md20020085 -
Insects Apr 2015The scientific community working in the field of insect pathology is experiencing an increasing academic and industrial interest in the discovery and development of new... (Review)
Review
The scientific community working in the field of insect pathology is experiencing an increasing academic and industrial interest in the discovery and development of new bioinsecticides as environmentally friendly pest control tools to be integrated, in combination or rotation, with chemicals in pest management programs. In this scientific context, market data report a significant growth of the biopesticide segment. Acquisition of new technologies by multinational Ag-tech companies is the center of the present industrial environment. This trend is in line with the requirements of new regulations on Integrated Pest Management. After a few decades of research on microbial pest management dominated by Bacillus thuringiensis (Bt), novel bacterial species with innovative modes of action are being discovered and developed into new products. Significant cases include the entomopathogenic nematode symbionts Photorhabdus spp. and Xenorhabdus spp., Serratia species, Yersinia entomophaga, Pseudomonas entomophila, and the recently discovered Betaproteobacteria species Burkholderia spp. and Chromobacterium spp. Lastly, Actinobacteria species like Streptomyces spp. and Saccharopolyspora spp. have gained high commercial interest for the production of a variety of metabolites acting as potent insecticides. With the aim to give a timely picture of the cutting-edge advancements in this renewed research field, different representative cases are reported and discussed.
PubMed: 26463190
DOI: 10.3390/insects6020352 -
PLoS Pathogens Jun 2022Arboviruses are etiological agents of various severe human diseases that place a tremendous burden on global public health and the economy; compounding this issue is the...
Arboviruses are etiological agents of various severe human diseases that place a tremendous burden on global public health and the economy; compounding this issue is the fact that effective prophylactics and therapeutics are lacking for most arboviruses. Herein, we identified 2 bacterial lipases secreted by a Chromobacterium bacterium isolated from Aedes aegypti midgut, Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with broad-spectrum virucidal activity against mosquito-borne viruses, such as dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), yellow fever virus (YFV) and Sindbis virus (SINV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation in the lipase motif of CbAE-1 fully abrogated the virucidal ability. Furthermore, CbAEs also exert lipase-dependent entomopathogenic activity in mosquitoes. The anti-arboviral and entomopathogenic properties of CbAEs render them potential candidates for the development of novel transmission control strategies against vector-borne diseases.
Topics: Aedes; Animals; Arboviruses; Dengue Virus; Humans; Lipase; Mosquito Vectors; Zika Virus; Zika Virus Infection
PubMed: 35679229
DOI: 10.1371/journal.ppat.1010552 -
Journal, Genetic Engineering &... Oct 2021Chromobacterium species, through their bioactive molecules, help in combating biotic and abiotic stresses in plants and humans. The present study was aimed to identify,...
BACKGROUND
Chromobacterium species, through their bioactive molecules, help in combating biotic and abiotic stresses in plants and humans. The present study was aimed to identify, characterize and preserve in natural gums the violet-pigmented bacterial isolate TRFM-24 recovered from the rhizosphere soil of rice collected from Tripura state.
RESULTS
Based on morphological, biochemical and 16S rRNA gene sequencing, the isolate TFRM-24 was identified as Chromobacterium violaceum (NAIMCC-B-02276; MCC 4212). The bacterium is saprophytic, free living and Gram negative. The strain was found positive for production of IAA, cellulase, xylanase and protease, and showed tolerance to salt (2.5%) and drought (-1.2 MPa). However, it showed poor biocontrol activity against soil-borne phytopathogens and nutrient-solubilizing abilitiets. C. violaceum strain TRFM-24 did not survive on tryptic soya agar (TSA) beyond 12 days between 4 and 32 °C temperature hence a method of preservation of this bacterium was attempted using different natural gums namely Acacia nilotica (babul), Anogeissus latifolia (dhavda), Boswellia serrata (salai) and Butea monosperma (palash) under different temperature regime (6-32 °C). The bacterium survived in babul gum (gum acacia), dhavda and salai solution at room temperature beyond a year.
CONCLUSION
Based on polyphasic approach, a violet-pigmented isolate TRFM-24 was identified as Chromobacterim violaceum which possessed some attributes of plant and human importance. Further, a simple and low-cost preservation method of strain TRFM-24 at room temperature was developed using natural gums such as babul, dhavda and salai gums which may be the first report to our knowledge.
PubMed: 34596780
DOI: 10.1186/s43141-021-00241-z -
BioMed Research International 2015Violacein-producing bacteria, with their striking purple hues, have undoubtedly piqued the curiosity of scientists since their first discovery. The bisindole violacein... (Review)
Review
Violacein-producing bacteria, with their striking purple hues, have undoubtedly piqued the curiosity of scientists since their first discovery. The bisindole violacein is formed by the condensation of two tryptophan molecules through the action of five proteins. The genes required for its production, vioABCDE, and the regulatory mechanisms employed have been studied within a small number of violacein-producing strains. As a compound, violacein is known to have diverse biological activities, including being an anticancer agent and being an antibiotic against Staphylococcus aureus and other Gram-positive pathogens. Identifying the biological roles of this pigmented molecule is of particular interest, and understanding violacein's function and mechanism of action has relevance to those unmasking any of its commercial or therapeutic benefits. Unfortunately, the production of violacein and its related derivatives is not easy and so various groups are also seeking to improve the fermentative yields of violacein through genetic engineering and synthetic biology. This review discusses the recent trends in the research and production of violacein by both natural and genetically modified bacterial strains.
Topics: Anti-Bacterial Agents; Chromobacterium; Fermentation; Genetic Engineering; Humans; Indoles; Pigments, Biological; Staphylococcus aureus; Tryptophan
PubMed: 26339614
DOI: 10.1155/2015/465056 -
Brazilian Journal of Microbiology :... Jun 2022Population of drug-resistant bacteria have increased at an alarming rate in the past few decades. The major reason for increasing drug resistance is the lack of new...
Population of drug-resistant bacteria have increased at an alarming rate in the past few decades. The major reason for increasing drug resistance is the lack of new antibiotics and limited drug targets. It has therefore been a vital task to develop new antibiotics with different drug targets. Two such targets are biofilm formation and quorum sensing. Quorum sensing is cell to cell communication used by bacteria that initiates many important survival processes and aids in establishing pathogenesis. Both biofilm and quorum sensing are inter-related processes and play a major role in physiological and pathogenesis processes. In this study, five novel imidazole derivatives (IMA-1-IMA-5) were synthesised and tested for their antibacterial and anti-quorum sensing activities against Chromobacterium violaceum using different in silico and in vitro techniques following the standard protocols. In silico results revealed that all compounds were able to effectively bind to and interact sufficiently with the target protein CviR. CviR is a protein to which autoinducers bind to initiate the quorum sensing process. In silico results also revealed that the compounds generated favourable structural dynamics implying that the compounds would be able to effectively bind to CviR and inhibit quorum sensing. Susceptibility results revealed that IMA-1 is the most active of all the derivatives against both planktonic cells and biofilms. Qualitative and quantitative evaluation of anti-quorum sensing activity at sub-inhibitory concentrations of these compounds also revealed high activity for IMA-1. Down-regulation of most of the quorum sensing genes when cells were treated with the test compounds affirmed the high anti-quorum sensing activities of these compounds. The results from this study are promising and urges on the use of anti-quorum sensing and biofilm disrupting molecules to combat multi-drug resistance problem.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Biofilms; Chromobacterium; Drug Discovery; Imidazoles; Pseudomonas aeruginosa; Quorum Sensing
PubMed: 35301694
DOI: 10.1007/s42770-022-00702-8 -
MBio Jun 2022Blocking host cell death is an important virulence strategy employed by many bacterial pathogens. We recently reported that Shigella flexneri inhibits host pyroptosis by...
Blocking host cell death is an important virulence strategy employed by many bacterial pathogens. We recently reported that Shigella flexneri inhibits host pyroptosis by delivering a type III secretion system (T3SS) effector OspC3 that catalyzes a novel arginine ADP-riboxanation modification on caspase-4/11. Here, we investigated the OspC3 homologue CopC from Chromobacterium violaceum, an opportunistic but sometimes deadly bacterial pathogen. CopC bears the same arginine ADP-riboxanase activity as OspC3, but with a different substrate specificity. Through proteomic analysis, we first identified host calmodulin (CaM) as a binding partner of CopC. The analyses additionally revealed that CopC preferably modifies apoptotic caspases including caspase-7, -8 and -9. This results in suppression of both extrinsic and intrinsic apoptosis programs in C. violaceum-infected cells. Biochemical reconstitution showed that CopC requires binding to CaM, specifically in the calcium-free state, to achieve efficient ADP-riboxanation of the caspases. We determined crystal structure of the CaM-CopC-CASP7 ternary complex, which illustrates the caspase recognition mechanism and a unique CaM-binding mode in CopC. Structure-directed mutagenesis validated the functional significance of CaM binding for stimulating CopC modification of its caspase substrates. CopC adopts an ADP-ribosyltransferase-like fold with a unique His-Phe-Glu catalytic triad, featuring two acidic residues critical for site-specific arginine ADP-riboxanation. Our study expands and deepens our understanding of the OspC family of ADP-riboxanase effectors. Programmed cell death is a suicidal defense mechanism for eukaryotes to combat pathogen infection. In the evolutionary arms race with the host, bacteria are endowed with ingenious tactics to block host cell death to facilitate their replication. Here, we report that the C. violaceum effector CopC ADP-riboxanates caspase-7/8/9, enabled by interacting with the host factor calmodulin, to block host cell apoptosis, illustrating a unique and sophisticated strategy adopted by the pathogen to counteract host defense.
Topics: Adenosine Diphosphate; Arginine; Calmodulin; Caspase 7; Caspases; Chromobacterium; Humans; Proteomics
PubMed: 35446120
DOI: 10.1128/mbio.00690-22 -
Research in Microbiology 2022This study reports the isolation of a new Chromobacterium haemolyticum strain named WI5 from a hydroponic farming facility. WI5 exhibited remarkable bacterial...
This study reports the isolation of a new Chromobacterium haemolyticum strain named WI5 from a hydroponic farming facility. WI5 exhibited remarkable bacterial antagonistic properties, eliminating Salmonella, Escherichia coli, Listeria monocytogenes and Staphylococcus aureus (initial inoculum load ∼10 CFU/ml) in dual-species co-culture biofilms. Antagonism was strictly contact-dependent and highly influenced by nutrient availability. Next, we identified a complete suite of putative Type VI secretion system (T6SS) genes in the WI5 genome, annotated the gene locus architecture, and determined the crystal structure of hallmark T6SS tube protein Hcp1, which revealed a hexameric ring structure with an outer and inner diameter of 77 and 45 Å, respectively. Structural comparison with homologs showed differences in the key loops connecting the β-strands in which the conserved residues are located, suggesting a role of these residues in the protein function. The T6SS is well-known to facilitate interbacterial competition, and the putative T6SS characterized herein might be responsible for the remarkable antagonism by C. haemolyticum WI5. Collectively, these findings shed light on the nature of bacterial antagonism and a putative key virulence determinant of C. haemolyticum, which might aid in further understanding its potential ecological role in natural habitats.
Topics: Bacterial Proteins; Chromobacterium; Escherichia coli; Type VI Secretion Systems; Virulence Factors
PubMed: 34906677
DOI: 10.1016/j.resmic.2021.103918