Abstract:
UNLABELLED:Clostridium perfringens enterotoxin (CPE) contributes to several important human gastrointestinal (GI) diseases. This toxin and its derivatives are also being explored for translational applications, i.e., cancer therapy or drug delivery. Some, but not all, members of the 24-member claudin (Cldn) family of mammalian tight junction proteins can serve as CPE receptors. Among the human Cldns (hCldns), hCldn-3 and -4 are known to convey CPE sensitivity when expressed by fibroblast transfectants. However, other Cldns are also reportedly expressed in the intestines, where they might contribute to natural CPE-mediated GI disease, and in other organs, where they might react with CPE-based therapeutics. Therefore, the current study assessed whether two additional hCldns beside hCldn-3 and -4 are also functional CPE receptors. Using Cldn-expressing transfectants, hCldn-8 and -14 were shown to convey CPE-mediated cytotoxicity at pathophysiologically relevant concentrations of this toxin, although ~2-to-10-fold less efficiently than hCldn-4. Site-directed mutagenesis then demonstrated that the N(146) residue in hCldn-14 and the S(151) residue in hCldn-8 are largely responsible for modulating the weaker CPE binding properties of hCldn-8 and -14 versus hCldn-4, which broadens understanding of Cldn:CPE binding interactions. Since Cldn-8 and -14 are reportedly expressed in mammalian intestines, the current results support the possibility that these two hCldns contribute to natural CPE-mediated gastrointestinal disease and could be CPE-based therapeutic targets for cancers overexpressing those claudins. However, these results also suggest caution during therapeutic use of CPE, which might trigger toxic side effects in normal human tissues producing hCldn-8 or -14, as well as in those producing hCldn-3 or -4. IMPORTANCE:Clostridium perfringens enterotoxin (CPE) is responsible for the gastrointestinal symptoms of the second-most-common bacterial food-borne illness and is also being explored for use as a cancer therapeutic or for increasing drug delivery. Until now, the only known human CPE receptors were claudin-3 and -4. This work shows that human claudin-8 and -14 can also bind CPE and convey cytotoxicity, although slightly less efficiently than claudin-3 and -4. The claudin-8 and -14 residues responsible for this weaker CPE binding were identified, shedding new light on CPE:claudin interactions.
journal_name
mBiojournal_title
mBioauthors
Shrestha A,McClane BAdoi
10.1128/mBio.00594-12subject
Has Abstractpub_date
2013-01-15 00:00:00issue
1issn
2150-7511pii
mBio.00594-12journal_volume
4pub_type
杂志文章相关文献
mBio文献大全abstract::Pseudomonas aeruginosa produces an extracellular biofilm matrix that consists of nucleic acids, exopolysaccharides, lipid vesicles, and proteins. In general, the protein component of the biofilm matrix is poorly defined and understudied relative to the other major matrix constituents. While matrix proteins have been s...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00543-18
更新日期:2018-04-10 00:00:00
abstract::Viral 2',5'-phosphodiesterases (2',5'-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN) by degrading 2',5'-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) s...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01312-14
更新日期:2014-07-01 00:00:00
abstract::Bacteria of the phylum Bacteroidetes, including commensal organisms and opportunistic pathogens, harbor abundant surface-exposed multiprotein membrane complexes (Sus-like systems) involved in carbohydrate acquisition. These complexes have been mostly linked to commensalism, and in some instances, they have also been s...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01232-16
更新日期:2016-10-25 00:00:00
abstract::ABSTRACT The type VII secretion systems are conserved across mycobacterial species and in many Gram-positive bacteria. While the well-characterized Esx-1 pathway is required for the virulence of pathogenic mycobacteria and conjugation in the model organism Mycobacterium smegmatis, Esx-3 contributes to mycobactin-media...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01073-14
更新日期:2014-05-06 00:00:00
abstract::Exudative cutaneous ulcers (CU) in yaws-endemic areas are associated with Treponema pallidum subsp. pertenue (TP) and Haemophilus ducreyi (HD), but one-third of CU cases are idiopathic (IU). Using mass drug administration (MDA) of azithromycin, a yaws eradication campaign on Lihir Island in Papua New Guinea reduced bu...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.03162-20
更新日期:2021-01-12 00:00:00
abstract::Host-associated microbial communities are shaped by extrinsic and intrinsic factors to the holobiont organism. Environmental factors and microbe-microbe interactions act simultaneously on the microbial community structure, making the microbiome dynamics challenging to predict. The coral microbiome is essential to the ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02691-19
更新日期:2020-03-03 00:00:00
abstract:UNLABELLED:Mammalian lipopolysaccharide (LPS) binding proteins (LBPs) occur mainly in extracellular fluids and promote LPS delivery to specific host cell receptors. The function of LBPs has been studied principally in the context of host defense; the possible role of LBPs in nonpathogenic host-microbe interactions has ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01193-15
更新日期:2015-10-13 00:00:00
abstract::Once HIV-1 enters a cell, the viral core is uncoated by a poorly understood mechanism and the HIV-1 genomic RNA is reverse transcribed into DNA. Host cell factors are essential for these processes, although very few reverse transcription complex binding host cell factors have been convincingly shown to affect uncoatin...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00316-18
更新日期:2018-03-27 00:00:00
abstract::Transposon insertion sequencing (TIS) is a powerful high-throughput genetic technique that is transforming functional genomics in prokaryotes, because it enables genome-wide mapping of the determinants of fitness. However, current approaches for analyzing TIS data assume that selective pressures are constant over time...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01581-17
更新日期:2017-10-03 00:00:00
abstract::The clonal population structure of Candida albicans suggests that (para)sexual recombination does not play an important role in the lifestyle of this opportunistic fungal pathogen, an assumption that is strengthened by the fact that most C. albicans strains are heterozygous at the mating type locus (MTL) and therefore...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02740-18
更新日期:2019-02-05 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::Uropathogenic Escherichia coli (UPEC) is the most common etiologic agent of uncomplicated urinary tract infection (UTI). An important mechanism of gene regulation in UPEC is phase variation that involves inversion of a promoter-containing DNA element via enzymatic activity of tyrosine recombinases, resulting in biphas...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01360-18
更新日期:2018-08-07 00:00:00
abstract::Colicins are toxins produced and released by Enterobacteriaceae to kill competitors in the gut. While group A colicins employ a division of labor strategy to liberate the toxin into the environment via colicin-specific lysis, group B colicin systems lack cognate lysis genes. In Salmonella enterica serovar Typhimurium ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00912-20
更新日期:2020-07-21 00:00:00
abstract::Chlamydiales species are obligate intracellular bacteria lacking a classical peptidoglycan sacculus but relying on peptidoglycan synthesis for cytokinesis. While septal peptidoglycan biosynthesis seems to be regulated by MreB actin and its membrane anchor RodZ rather than FtsZ tubulin in Chlamydiales, the mechanism of...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01128-19
更新日期:2019-07-16 00:00:00
abstract:UNLABELLED:Fast, definitive diagnosis of Creutzfeldt-Jakob disease (CJD) is important in assessing patient care options and transmission risks. Real-time quaking-induced conversion (RT-QuIC) assays of cerebrospinal fluid (CSF) and nasal-brushing specimens are valuable in distinguishing CJD from non-CJD conditions but h...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02451-14
更新日期:2015-01-20 00:00:00
abstract:UNLABELLED:Ebola viruses (EBOV) cause severe disease in humans and nonhuman primates with high mortality rates and continue to emerge in new geographic locations, including several countries in West Africa, the site of a large ongoing outbreak. Phosphorodiamidate morpholino oligomers (PMOs) are synthetic antisense mole...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02344-14
更新日期:2015-02-10 00:00:00
abstract:UNLABELLED:The urinary tract is one of the most frequent sites of bacterial infection in humans. Uropathogenic Escherichia coli (UPEC) strains are the leading cause of urinary tract infections (UTIs) and are responsible for greater than 80% of uncomplicated cases in adults. Infection of the urinary tract occurs in an a...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00303-11
更新日期:2012-02-07 00:00:00
abstract::The members of the OM43 clade of Betaproteobacteria are abundant coastal methylotrophs with a range of carbon-utilizing capabilities. However, their underlying transcriptional and metabolic responses to shifting conditions or different carbon substrates remain poorly understood. We examined the transcriptional dynamic...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01279-16
更新日期:2016-11-22 00:00:00
abstract:UNLABELLED:Staphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing life-threatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virulence gene expressio...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00459-12
更新日期:2013-01-02 00:00:00
abstract:UNLABELLED:A 32-nucleotide (nt) RNA motif located at the 3' end of the transmissible gastroenteritis coronavirus (TGEV) genome was found to specifically interact with the host proteins glutamyl-prolyl-tRNA synthetase (EPRS) and arginyl-tRNA synthetase (RRS). This RNA motif has high homology in sequence and secondary st...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00105-15
更新日期:2015-03-10 00:00:00
abstract::Members of the genus Mycobacterium are the most prevalent cause of infectious diseases. Mycobacteria have a complex cell envelope containing a peptidoglycan layer and an additional arabinogalactan polymer to which a mycolic acid bilayer is linked; this complex, multilayered cell wall composition (mAGP) is conserved am...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02213-16
更新日期:2017-02-07 00:00:00
abstract:UNLABELLED:Enterococcus faecium, natively a gut commensal organism, emerged as a leading cause of multidrug-resistant hospital-acquired infection in the 1980s. As the living record of its adaptation to changes in habitat, we sequenced the genomes of 51 strains, isolated from various ecological environments, to understa...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00534-13
更新日期:2013-08-20 00:00:00
abstract::Sodium-translocating NADH:quinone oxidoreductase (Na+-NQR) functions as a unique redox-driven sodium pump, generating membrane potential, which is related to aminoglycoside antibiotic resistance. However, whether it modulates other metabolisms to confer antibiotic resistance is unknown. The present study showed that l...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02086-20
更新日期:2020-11-17 00:00:00
abstract:UNLABELLED:Particular types of hormonal contraceptives (HCs) and genital tract infections have been independently associated with risk of HIV-1 acquisition. We examined whether immunity in women using injectable depot medroxyprogesterone acetate (DMPA), combined oral contraceptives (COC), or no HCs differs by the prese...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00221-15
更新日期:2015-09-01 00:00:00
abstract::The flagellar motor can spin in both counterclockwise (CCW) and clockwise (CW) directions. The flagellar motor consists of a rotor and multiple stator units, which act as a proton channel. The rotor is composed of the transmembrane MS ring made of FliF and the cytoplasmic C ring consisting of FliG, FliM, and FliN. The...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00079-19
更新日期:2019-04-02 00:00:00
abstract:UNLABELLED:Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) a...
journal_title:mBio
pub_type: 杂志文章,随机对照试验
doi:10.1128/mBio.00076-13
更新日期:2013-04-16 00:00:00
abstract:UNLABELLED:Rarely, if ever, has a single bacterial cell been confirmed to simultaneously host two fundamentally different predators. Two such predators are viruses and the predatory prokaryotes known as Bdellovibrio and like organisms. Viruses or bacteriophage are particles requiring prey cells in an active metabolic s...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00051-12
更新日期:2012-04-17 00:00:00
abstract::The facultative intracellular pathogen Listeria monocytogenes, like many related Firmicutes, uses the nucleotide second messenger cyclic di-AMP (c-di-AMP) to adapt to changes in nutrient availability, osmotic stress, and the presence of cell wall-acting antibiotics. In rich medium, c-di-AMP is essential; however, muta...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01625-20
更新日期:2020-08-25 00:00:00
abstract:UNLABELLED:Singlet oxygen ((1)O(2)) is a reactive oxygen species generated by energy transfer from one or more excited donors to molecular oxygen. Many biomolecules are prone to oxidation by (1)O(2), and cells have evolved systems to protect themselves from damage caused by this compound. One way that the photosyntheti...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00541-12
更新日期:2013-01-08 00:00:00
abstract::The alarmone (p)ppGpp plays pivotal roles in basic bacterial stress responses by increasing tolerance of various nutritional limitations and chemical insults, including antibiotics. Despite intensive studies since (p)ppGpp was discovered over 4 decades ago, (p)ppGpp binding proteins have not been systematically identi...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02188-17
更新日期:2018-03-06 00:00:00