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Microbiology Spectrum Nov 2019As obligate anaerobes, clostridial pathogens depend on their metabolically dormant, oxygen-tolerant spore form to transmit disease. However, the molecular mechanisms by... (Review)
Review
As obligate anaerobes, clostridial pathogens depend on their metabolically dormant, oxygen-tolerant spore form to transmit disease. However, the molecular mechanisms by which those spores germinate to initiate infection and then form new spores to transmit infection remain poorly understood. While sporulation and germination have been well characterized in and , striking differences in the regulation of these processes have been observed between the bacilli and the clostridia, with even some conserved proteins exhibiting differences in their requirements and functions. Here, we review our current understanding of how clostridial pathogens, specifically , , and , induce sporulation in response to environmental cues, assemble resistant spores, and germinate metabolically dormant spores in response to environmental cues. We also discuss the direct relationship between toxin production and spore formation in these pathogens.
Topics: Animals; Clostridium; Clostridium Infections; Humans; Spores, Bacterial
PubMed: 31858953
DOI: 10.1128/microbiolspec.GPP3-0017-2018 -
Microbiology Spectrum Aug 2014Clostridia are Gram-positive, anaerobic, endospore-forming bacteria, incapable of dissimilatory sulfate reduction. Comprising approximately 180 species, the genus... (Review)
Review
Clostridia are Gram-positive, anaerobic, endospore-forming bacteria, incapable of dissimilatory sulfate reduction. Comprising approximately 180 species, the genus Clostridium is one of the largest bacterial genera. Physiology is mostly devoted to acid production. Numerous pathways are known, such as the homoacetate fermentation by acetogens, the propionate fermentation by Clostridium propionicum, and the butyrate/butanol fermentation by C. acetobutylicum, a well-known solvent producer. Clostridia degrade sugars, alcohols, amino acids, purines, pyrimidines, and polymers such as starch and cellulose. Energy conservation can be performed by substrate-level phosphorylation as well as by the generation of ion gradients. Endospore formation resembles the mechanism elucidated in Bacillus. Morphology, contents, and properties of spores are very similar to bacilli endospores. Sporulating clostridia usually form swollen mother cells and accumulate the storage substance granulose. However, clostridial sporulation differs by not employing the so-called phosphorelay. Initiation starts by direct phosphorylation of the master regulator Spo0A. The cascade of sporulation-specific sigma factors is again identical to what is known from Bacillus. The onset of sporulation is coupled in some species to either solvent (acetone, butanol) or toxin (e.g., C. perfringens enterotoxin) formation. The germination of spores is often induced by various amino acids, often in combination with phosphate and sodium ions. In medical applications, C. butyricum spores are used as a C. difficile prophylaxis and as treatment against diarrhea. Recombinant spores are currently under investigation and testing as antitumor agents, because they germinate only in hypoxic tissues (i.e., tumor tissue), allowing precise targeting and direct killing of tumor cells.
Topics: Anaerobiosis; Carboxylic Acids; Clostridium; Fermentation; Gene Expression Regulation, Bacterial; Spores, Bacterial
PubMed: 26104199
DOI: 10.1128/microbiolspec.TBS-0010-2012 -
Microbiology Spectrum Oct 2014Spores of various Bacillus and Clostridium species are among the most resistant life forms known. Since the spores of some species are causative agents of much food... (Review)
Review
Spores of various Bacillus and Clostridium species are among the most resistant life forms known. Since the spores of some species are causative agents of much food spoilage, food poisoning, and human disease, and the spores of Bacillus anthracis are a major bioweapon, there is much interest in the mechanisms of spore resistance and how these spores can be killed. This article will discuss the factors involved in spore resistance to agents such as wet and dry heat, desiccation, UV and γ-radiation, enzymes that hydrolyze bacterial cell walls, and a variety of toxic chemicals, including genotoxic agents, oxidizing agents, aldehydes, acid, and alkali. These resistance factors include the outer layers of the spore, such as the thick proteinaceous coat that detoxifies reactive chemicals; the relatively impermeable inner spore membrane that restricts access of toxic chemicals to the spore core containing the spore's DNA and most enzymes; the low water content and high level of dipicolinic acid in the spore core that protect core macromolecules from the effects of heat and desiccation; the saturation of spore DNA with a novel group of proteins that protect the DNA against heat, genotoxic chemicals, and radiation; and the repair of radiation damage to DNA when spores germinate and return to life. Despite their extreme resistance, spores can be killed, including by damage to DNA, crucial spore proteins, the spore's inner membrane, and one or more components of the spore germination apparatus.
Topics: Bacillus; Clostridium; Desiccation; Enzymes; Hot Temperature; Inorganic Chemicals; Microbial Viability; Organic Chemicals; Spores, Bacterial
PubMed: 26104355
DOI: 10.1128/microbiolspec.TBS-0003-2012 -
Biochimica Et Biophysica Acta.... Sep 2021Studies of the lipidomes of twenty-one species of clostridia have revealed considerable diversity. Even among those species now defined as Clostridium sensu stricto,... (Review)
Review
Studies of the lipidomes of twenty-one species of clostridia have revealed considerable diversity. Even among those species now defined as Clostridium sensu stricto, which are related to Clostridium butyricum, the type species, lipid analysis has shown that a number of distinct clades have characteristic polar lipids. All species of Clostridium sensu stricto have phosphatidylethanolamine, phosphatidylglycerol and cardiolipin which are present as all acyl or alk-1'-enyl acyl (plasmalogen) species. In addition, almost every clade has specialized polar lipids. For example, the group closely related to Clostridium beijerinckii and several other solventogenic species has glycerol acetals of plasmenylethanolamine, which protects the membrane bilayer arrangement when the lipids are highly unsaturated or in the presence of solvents. The group related to Clostridium novyi has aminoacyl-phosphatidylglycerol, which protects these pathogens from cationic antimicrobial peptides (CAMPs) of innate immunity. Clostridium botulinum species, which fall into several groups, align with these clades, and have the same specific lipids. This review will present the current state of knowledge on clostridial lipids.
Topics: Clostridium; Lipidomics
PubMed: 33974975
DOI: 10.1016/j.bbalip.2021.158966 -
Microbiology and Molecular Biology... Mar 2015Bacillus and Clostridium organisms initiate the sporulation process when unfavorable conditions are detected. The sporulation process is a carefully orchestrated cascade... (Review)
Review
Bacillus and Clostridium organisms initiate the sporulation process when unfavorable conditions are detected. The sporulation process is a carefully orchestrated cascade of events at both the transcriptional and posttranslational levels involving a multitude of sigma factors, transcription factors, proteases, and phosphatases. Like Bacillus genomes, sequenced Clostridium genomes contain genes for all major sporulation-specific transcription and sigma factors (spo0A, sigH, sigF, sigE, sigG, and sigK) that orchestrate the sporulation program. However, recent studies have shown that there are substantial differences in the sporulation programs between the two genera as well as among different Clostridium species. First, in the absence of a Bacillus-like phosphorelay system, activation of Spo0A in Clostridium organisms is carried out by a number of orphan histidine kinases. Second, downstream of Spo0A, the transcriptional and posttranslational regulation of the canonical set of four sporulation-specific sigma factors (σ(F), σ(E), σ(G), and σ(K)) display different patterns, not only compared to Bacillus but also among Clostridium organisms. Finally, recent studies demonstrated that σ(K), the last sigma factor to be activated according to the Bacillus subtilis model, is involved in the very early stages of sporulation in Clostridium acetobutylicum, C. perfringens, and C. botulinum as well as in the very late stages of spore maturation in C. acetobutylicum. Despite profound differences in initiation, propagation, and orchestration of expression of spore morphogenetic components, these findings demonstrate not only the robustness of the endospore sporulation program but also the plasticity of the program to generate different complex phenotypes, some apparently regulated at the epigenetic level.
Topics: Bacillus; Bacillus subtilis; Clostridium; Clostridium acetobutylicum; Clostridium botulinum; Clostridium perfringens; Gene Expression Regulation, Bacterial; Histidine Kinase; Phenotype; Protein Kinases; Sigma Factor; Spores, Bacterial; Transcription Factors
PubMed: 25631287
DOI: 10.1128/MMBR.00025-14 -
Journal of Bacteriology Oct 2016Many anaerobic spore-forming clostridial species are pathogenic, and some are industrially useful. Although many are strict anaerobes, the bacteria persist under aerobic... (Review)
Review
Many anaerobic spore-forming clostridial species are pathogenic, and some are industrially useful. Although many are strict anaerobes, the bacteria persist under aerobic and growth-limiting conditions as multilayered metabolically dormant spores. For many pathogens, the spore form is what most commonly transmits the organism between hosts. After the spores are introduced into the host, certain proteins (germinant receptors) recognize specific signals (germinants), inducing spores to germinate and subsequently grow into metabolically active cells. Upon germination of the spore into the metabolically active vegetative form, the resulting bacteria can colonize the host and cause disease due to the secretion of toxins from the cell. Spores are resistant to many environmental stressors, which make them challenging to remove from clinical environments. Identifying the conditions and the mechanisms of germination in toxin-producing species could help develop affordable remedies for some infections by inhibiting germination of the spore form. Unrelated to infectious disease, spore formation in species used in the industrial production of chemicals hinders the optimum production of the chemicals due to the depletion of the vegetative cells from the population. Understanding spore germination in acetone-butanol-ethanol-producing species can help boost the production of chemicals, leading to cheaper ethanol-based fuels. Until recently, clostridial spore germination is assumed to be similar to that of Bacillus subtilis However, recent studies in Clostridium difficile shed light on a mechanism of spore germination that has not been observed in any endospore-forming organisms to date. In this review, we focus on the germinants and the receptors recognizing these germinants in various clostridial species.
Topics: Animals; Bacterial Proteins; Clostridium; Clostridium Infections; Humans; Spores, Bacterial
PubMed: 27432831
DOI: 10.1128/JB.00405-16 -
Lipids Aug 2019The lipidomes of Clostridium fallax and Clostridium cadaveris were studied using thin-layer chromatography (TLC) and normal phase liquid chromatography/mass spectrometry...
The lipidomes of Clostridium fallax and Clostridium cadaveris were studied using thin-layer chromatography (TLC) and normal phase liquid chromatography/mass spectrometry (NPLC/MS). Both species contain diradylglycerol (DRG), monohexosyldiradylglycerol (MHDRG), monohexosyl monoacylglycerol (MHMAG), phosphatidylglycerol (PtdGro), and phosphatidylethanolamine (PtdEtn). DRG, MHDRG, PtdEtn, and PtdGro are present in both diacyl and alk-1-enyl acyl (plasmalogen) forms. Both species contain cardiolipin (Ptd Gro), which is present in tetraacyl, monoalkenyl-triacyl, and dialkenyl-diacyl forms. Both species contain small amounts of phosphatidylcholine (PtdCho). The presence of octadecadienoic (18:2) acyl chains in some PtdCho species indicates that they arise from the medium because no 18:2 is seen in the other lipids and clostridia generally lack the capacity to synthesize polyunsaturated fatty acids. The major lipidomic differences between these two species are that C. fallax contains a glycerolacetal of plasmenylethanolamine while C. cadaveris contains an ethanolamine-phosphate-modified diacylglycerol. The significance of these lipid compositions is discussed.
Topics: Chromatography, Liquid; Clostridium; Lipidomics; Lipids; Mass Spectrometry; Molecular Structure
PubMed: 31368115
DOI: 10.1002/lipd.12181 -
Research in Microbiology May 2015Sporulation is an important strategy for certain bacterial species within the phylum Firmicutes to survive longer periods of time in adverse conditions. All... (Review)
Review
Sporulation is an important strategy for certain bacterial species within the phylum Firmicutes to survive longer periods of time in adverse conditions. All spore-forming bacteria have two phases in their life; the vegetative form, where they can maintain all metabolic activities and replicate to increase numbers, and the spore form, where no metabolic activities exist. Although many essential components of sporulation are conserved among the spore-forming bacteria, there are differences in the regulation and the pathways among different genera, even at the species level. While we have gained much information from the most studied spore-forming bacterial genus, Bacillus, we still lack an in-depth understanding of spore formation in the genus Clostridium. Clostridium and Bacillus share the master regulator of sporulation, Spo0A, and its downstream pathways, but there are differences in the activation of the Spo0A pathway. While Bacillus species use a multi-component phosphorylation pathway for phosphorylation of Spo0A, termed phosphorelay, such a phosphorelay system is absent in Clostridium. On the other hand, a number of genes regulated by the different sporulation-specific transcription factors are conserved between different Clostridium and Bacillus species. In this review, we discuss the recent findings on Clostridium sporulation and compare the sporulation mechanism in Clostridium and Bacillus.
Topics: Clostridium; Gene Expression Regulation, Bacterial; Gene Regulatory Networks; Metabolic Networks and Pathways; Spores, Bacterial; Transcriptional Activation
PubMed: 25541348
DOI: 10.1016/j.resmic.2014.12.001 -
Genome Biology and Evolution Oct 2017Clostridium species (particularly Clostridium difficile, Clostridium botulinum, Clostridium tetani and Clostridium perfringens) are associated with a range of human and...
Clostridium species (particularly Clostridium difficile, Clostridium botulinum, Clostridium tetani and Clostridium perfringens) are associated with a range of human and animal diseases. Several other species including Clostridium tertium, Clostridium cadaveris, and Clostridium paraputrificum have also been linked with sporadic human infections, however there is very limited, or in some cases, no genomic information publicly available. Thus, we isolated one C. tertium strain, one C. cadaveris strain and three C. paraputrificum strains from preterm infants residing within neonatal intensive care units and performed Whole Genome Sequencing (WGS) using Illumina HiSeq. In this report, we announce the open availability of the draft genomes: C. tertium LH009, C. cadaveris LH052, C. paraputrificum LH025, C. paraputrificum LH058, and C. paraputrificum LH141. These genomes were checked for contamination in silico to ensure purity, and we confirmed species identity and phylogeny using both 16S rRNA gene sequences (from PCR and in silico) and WGS-based approaches. Average Nucleotide Identity (ANI) was used to differentiate genomes from their closest relatives to further confirm speciation boundaries. We also analysed the genomes for virulence-related factors and antimicrobial resistance genes, and detected presence of tetracycline and methicillin resistance, and potentially harmful enzymes, including multiple phospholipases and toxins. The availability of genomic data in open databases, in tandem with our initial insights into the genomic content and virulence traits of these pathogenic Clostridium species, should enable the scientific community to further investigate the disease-causing mechanisms of these bacteria with a view to enhancing clinical diagnosis and treatment.
Topics: Clostridium; Clostridium tertium; Feces; Genome, Bacterial; Humans; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Phylogeny
PubMed: 29044436
DOI: 10.1093/gbe/evx210 -
Journal of Microbiology and... Apr 2020A quantitative real-time polymerase chain reaction (QPCR) was applied to estimate biokinetic coefficients of and , which utilize protein as carbon source. Experimental...
A quantitative real-time polymerase chain reaction (QPCR) was applied to estimate biokinetic coefficients of and , which utilize protein as carbon source. Experimental data of changes in peptone concentration and 16S rRNA gene copy numbers of and were fitted to model. The fourth-order Runge-Kutta approximation with non-linear least squared analysis was employed to solve the ordinary differential equations to estimate biokinetic coefficients. The maximum specific growth rate (), half saturation concentration (), growth yield (), and decay coefficient () of and were 0.73 ± 0.05 and 1.35 ± 0.32 h, 6.07 ± 1.52 and 5.67 ± 1.53 g/L, 2.25 ± 0.75 × 10 and 7.92 ± 3.71 × 10 copies/g, 0.002 ± 0.003 and 0.002 ± 0.001 h, respectively. The theoretical specific growth rate of always exceeded than that of at peptone concentration higher than 3.62 g/L. When the influent peptone concentration was 5.0 g/L, the concentration of C.cadaveris gradually decreased to the steady value of 2.9 × 10 copies/mL at 4 hours HRT, which indicates 67.1% of the initial population reduction, but the wash out occurred at 1.9 and 3.2 hours HRTs. The 16S rRNA gene copy numbers of gradually decreased to steady values ranging from 1.1 × 10 to 2.9 × 10 copies/mL. species was predicted to wash out at an HRT of 1.6 h.
Topics: Batch Cell Culture Techniques; Biodegradation, Environmental; Bioreactors; Clostridium; Kinetics; Peptones; Proteins; RNA, Ribosomal, 16S
PubMed: 31986562
DOI: 10.4014/jmb.1908.08054