Abstract:
:Epsilon toxin (ETX), a pore-forming toxin produced by type B and D strains of Clostridium perfringens, mediates severe enterotoxemia in livestock and possibly plays a role in human disease. During enterotoxemia, the nearly inactive ETX prototoxin is produced in the intestines but then must be activated by proteolytic processing. The current study sought to examine ETX prototoxin processing and activation ex vivo using the intestinal contents of a goat, a natural host species for ETX-mediated disease. First, this study showed that the prototoxin has a KEIS N-terminal sequence with a molecular mass of 33,054 Da. When the activation of ETX prototoxin ex vivo by goat small intestinal contents was assessed by SDS-PAGE, the prototoxin was processed in a stepwise fashion into an ~27-kDa band or higher-molecular-mass material that could be toxin oligomers. Purified ETX corresponding to the ~27-kDa band was cytotoxic. When it was biochemically characterized by mass spectrometry, the copresence of three ETX species, each with different C-terminal residues, was identified in the purified ~27-kDa ETX preparation. Cytotoxicity of each of the three ETX species was then demonstrated using recombinant DNA approaches. Serine protease inhibitors blocked the initial proteotoxin processing, while carboxypeptidase inhibitors blocked further processing events. Taken together, this study provides important new insights indicating that, in the intestinal lumen, serine protease (including trypsin and possibly chymotrypsin) initiates the processing of the prototoxin but other proteases, including carboxypeptidases, then process the prototoxin into multiple active and stable species. Importance: Processing and activation by intestinal proteases is a prerequisite for ETX-induced toxicity. Previous studies had characterized the activation of ETX using only arbitrarily chosen amounts of purified trypsin and/or chymotrypsin. Therefore, the current study examined ETX activation ex vivo by natural host intestinal contents. These analyses demonstrated that (i) ETX processing in host intestinal contents occurs in an ordered, stepwise fashion, (ii) processing of prototoxin by host intestinal contents results in higher-molecular-mass material and 3 distinct ~27-kDa ETX species, and (iii) serine proteases, such as trypsin, chymotrypsin, and other proteases, including carboxypeptidases, play a role in the activation of ETX by intestinal contents. These studies provide new insights into the activation and processing of ETX and demonstrate that this process is more complicated than previously appreciated.
journal_name
mBiojournal_title
mBioauthors
Freedman JC,Li J,Uzal FA,McClane BAdoi
10.1128/mBio.01994-14subject
Has Abstractpub_date
2014-10-21 00:00:00pages
e01994-14issue
5issn
2150-7511pii
mBio.01994-14journal_volume
5pub_type
杂志文章相关文献
mBio文献大全abstract:UNLABELLED:In vivo transcriptional analyses of microbial pathogens are often hampered by low proportions of pathogen biomass in host organs, hindering the coverage of full pathogen transcriptome. We aimed to address the transcriptome profiles of Candida albicans, the most prevalent fungal pathogen in systemically infec...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00942-15
更新日期:2015-09-22 00:00:00
abstract:UNLABELLED:Streptococcus pneumoniae (pneumococcus) is a frequent colonizer of the nasopharynx and one of the leading causative agents of otitis media, pneumonia, and meningitis. The current literature asserts that S. pneumoniae is transmitted person to person via respiratory droplets; however, environmental surfaces (f...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00092-11
更新日期:2011-05-24 00:00:00
abstract::Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease afflicting hundreds of millions of people globally. A fundamental but poorly understood pathophysiological characteristic of chlamydial infection is the propensity to cause persistent in...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01902-20
更新日期:2020-08-18 00:00:00
abstract::With great apprehension, the world is now watching the birth of a novel pandemic already causing tremendous suffering, death, and disruption of normal life. Uncertainty and dread are exacerbated by the belief that what we are experiencing is new and mysterious. However, deadly pandemics and disease emergences are not ...
journal_title:mBio
pub_type: 历史文章,杂志文章,评审
doi:10.1128/mBio.00812-20
更新日期:2020-05-29 00:00:00
abstract::Bacteriophages are numerically the most abundant DNA-containing entities in the oligotrophic ocean, yet how specific phage populations vary over time and space remains to be fully explored. Here, we conducted a metagenomic time-series survey of double-stranded DNA phages throughout the water column in the North Pacifi...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01903-17
更新日期:2017-11-28 00:00:00
abstract::The genomes of actinomycetes contain numerous gene clusters potentially able to encode the production of many antibiotics and other specialized metabolites that are not expressed during growth under typical laboratory conditions. Undoubtedly, this reflects the soil habitat of these organisms, which is highly complex p...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00612-13
更新日期:2013-09-03 00:00:00
abstract:UNLABELLED:Candida albicans is a major life-threatening human fungal pathogen in the immunocompromised host. Host defense against systemic Candida infection relies heavily on the capacity of professional phagocytes of the innate immune system to ingest and destroy fungal cells. A number of pathogens, including C. albic...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01874-14
更新日期:2014-12-02 00:00:00
abstract:UNLABELLED:Competence for genetic transformation in Streptococcus pneumoniae develops in response to accumulation of a secreted peptide pheromone and was one of the initial examples of bacterial quorum sensing. Activation of this signaling system induces not only expression of the proteins required for transformation b...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00071-11
更新日期:2011-09-20 00:00:00
abstract::Silver (Ag+) and copper (Cu+) ions have been used for centuries in industry, as well as antimicrobial agents in agriculture and health care. Nowadays, Ag+ is also widely used in the field of nanotechnology. Yet, the underlying mechanisms driving toxicity of Ag+ ions in vivo are poorly characterized. It is well known t...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01535-18
更新日期:2018-11-20 00:00:00
abstract::Plant roots support complex microbial communities that can influence plant growth, nutrition, and health. While extensive characterizations of the composition and spatial compartmentalization of these communities have been performed in different plant species, there is relatively little known about the impact of abiot...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00764-17
更新日期:2017-07-18 00:00:00
abstract::E165R, a highly specific dUTP nucleotidohydrolase (dUTPase) encoded by the African swine fever virus (ASFV) genome, is required for productive replication of ASFV in swine macrophages. Here, we solved the high-resolution crystal structures of E165R in its apo state and in complex with its product dUMP. Structural anal...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02483-19
更新日期:2019-10-29 00:00:00
abstract::Phage therapy is a promising alternative to chemotherapeutic antibiotics for the treatment of bacterial infections. However, despite recent clinical uses of combinations of phages to treat multidrug-resistant infections, a mechanistic understanding of how bacteria evolve resistance against multiple phages is lacking, ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01652-19
更新日期:2019-09-24 00:00:00
abstract::Ocean viruses are ubiquitous and abundant and play important roles in global biogeochemical cycles by means of their mortality, horizontal gene transfer, and manipulation of host metabolism. However, the obstacles involved in linking viruses to their hosts in a high-throughput manner bottlenecks our ability to underst...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00373-12
更新日期:2012-10-30 00:00:00
abstract::Although the TEM-1 β-lactamase (BlaTEM-1) hydrolyzes penicillins and narrow-spectrum cephalosporins, organisms expressing this enzyme are typically susceptible to β-lactam/β-lactamase inhibitor combinations such as piperacillin-tazobactam (TZP). However, our previous work led to the discovery of 28 clinical isolates o...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00583-18
更新日期:2018-04-24 00:00:00
abstract::Mycoviruses infect fungi, and while most persist asymptomatically, there are examples of mycoviruses having both beneficial and detrimental effects on their host. Virus-infected Saccharomyces and Ustilago strains exhibit a killer phenotype conferring a growth advantage over uninfected strains and other competing yeast...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01534-20
更新日期:2020-09-01 00:00:00
abstract::As the GroES/GroEL chaperonin system is the only bacterial chaperone that is essential under all conditions, we have been interested in the development of GroES/GroEL inhibitors as potential antibiotics. Using Escherichia coli GroES/GroEL as a surrogate, we have discovered several classes of GroES/GroEL inhibitors tha...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02167-20
更新日期:2021-01-12 00:00:00
abstract::The invasion-associated type III secretion system (T3SS-1) of Salmonella enterica serotype Typhimurium (S. Typhimurium) activates the transcription factor NF-κB in tissue culture cells and induces inflammatory responses in animal models through unknown mechanisms. Here we show that bacterial delivery or ectopic expres...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00266-11
更新日期:2011-12-20 00:00:00
abstract::Mycobacterium bovis BCG is the only available vaccine for protection against tuberculosis (TB). While BCG protects children from severe disease, it has little impact on pulmonary disease in adults. A recombinant BCG vaccine BCG ΔureC::hly (strain VPM1002) is in advanced clinical trials and shows promise for improved v...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01370-16
更新日期:2016-08-30 00:00:00
abstract::Vibrio vulnificus, an opportunistic pathogen, is the causative agent of a life-threatening septicemia and a rising problem for aquaculture worldwide. The genetic factors that differentiate its clinical and environmental strains remain enigmatic. Furthermore, clinical strains have emerged from every clade of V. vulnifi...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02852-18
更新日期:2019-02-19 00:00:00
abstract:UNLABELLED:Diverse colony morphologies are a hallmark of Burkholderia pseudomallei recovered from infected patients. We observed that stresses that inhibit aerobic respiration shifted populations of B. pseudomallei from the canonical white colony morphotype toward two distinct, reversible, yet relatively stable yellow ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02462-14
更新日期:2015-02-03 00:00:00
abstract:UNLABELLED:Bacteria engage in chemical signaling, termed quorum sensing (QS), to mediate intercellular communication, mimicking multicellular organisms. The LuxR family of QS transcription factors regulates gene expression, coordinating population behavior by sensing endogenous acyl homoserine lactones (AHLs). However,...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02429-14
更新日期:2015-03-31 00:00:00
abstract:UNLABELLED:Cholera continues to be a global threat, with high rates of morbidity and mortality. In 2011, a cholera outbreak occurred in Palawan, Philippines, affecting more than 500 people, and 20 individuals died. Vibrio cholerae O1 was confirmed as the etiological agent. Source attribution is critical in cholera outb...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00047-15
更新日期:2015-04-21 00:00:00
abstract:UNLABELLED:Mycoplasma pneumoniae, a pathogenic bacterium, glides on host surfaces using a unique mechanism. It forms an attachment organelle at a cell pole as a protrusion comprised of knoblike surface structures and an internal core. Here, we analyzed the three-dimensional structure of the organelle in detail by elect...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00243-16
更新日期:2016-04-12 00:00:00
abstract:UNLABELLED:The bacterial flagellum is driven by a bidirectional rotary motor, which propels bacteria to swim through liquids or swarm over surfaces. While the functions of the major structural and regulatory components of the flagellum are known, the function of the well-conserved FliL protein is not. In Salmonella and...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02367-14
更新日期:2015-02-24 00:00:00
abstract:UNLABELLED:Human noroviruses (HuNoVs) cause significant morbidity and mortality worldwide. However, despite substantial efforts, a small-animal model for HuNoV has not been described to date. Since "humanized" mice have been successfully used to study human-tropic pathogens in the past, we challenged BALB/c mice defici...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00450-13
更新日期:2013-07-16 00:00:00
abstract:UNLABELLED:In infection experiments with genetically distinct Mycobacterium tuberculosis complex (MTBC) strains, we identified clade-specific virulence patterns in human primary macrophages and in mice infected by the aerosol route, both reflecting relevant model systems. Exclusively human-adapted M. tuberculosis linea...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00250-13
更新日期:2013-07-30 00:00:00
abstract::The opportunistic pathogen Pseudomonas aeruginosa is a leading cause of airway infection in cystic fibrosis (CF) patients. P. aeruginosa employs several hierarchically arranged and interconnected quorum sensing (QS) regulatory circuits to produce a battery of virulence factors such as elastase, phenazines, and rhamnol...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00532-20
更新日期:2020-04-07 00:00:00
abstract::Catabolite control protein A (CcpA) is the master regulator in Gram-positive bacteria that mediates carbon catabolite repression (CCR) and carbon catabolite activation (CCA), two fundamental regulatory mechanisms that enable competitive advantages in carbon catabolism. It is generally regarded that CcpA exerts its reg...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02004-16
更新日期:2017-01-24 00:00:00
abstract::The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in sup...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00809-18
更新日期:2018-05-22 00:00:00
abstract:UNLABELLED:Human immunodeficiency virus type 1 (HIV-1) Nef enhances virus replication and contributes to immune evasion in vivo, but the underlying molecular mechanisms remain incompletely defined. Nef interferes with host cell actin dynamics to restrict T lymphocyte responses to chemokine stimulation and T cell recept...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01309-15
更新日期:2015-09-08 00:00:00