Abstract:
:The cholesterol-dependent cytolysins (CDCs) are bacterial, β-barrel, pore-forming toxins. A central enigma of the pore-forming mechanism is how completion of the prepore is sensed to initiate its conversion to the pore. We identified a motif that is conserved between the CDCs and a diverse family of nearly 300 uncharacterized proteins present in over 220 species that span at least 10 bacterial and 2 eukaryotic phyla. Except for this motif, these proteins exhibit little similarity to the CDCs at the primary structure level. Studies herein show this motif is a critical component of the sensor that initiates the prepore-to-pore transition in the CDCs. We further show by crystallography, single particle analysis, and biochemical studies of one of these CDC-like (CDCL) proteins from Elizabethkingia anophelis, a commensal of the malarial mosquito midgut, that a high degree of structural similarity exists between the CDC and CDCL monomer structures and both form large oligomeric pore complexes. Furthermore, the conserved motif in the E. anophelis CDCL crystal structure occupies a nearly identical position and makes similar contacts to those observed in the structure of the archetype CDC, perfringolysin O (PFO). This suggests a common function in the CDCs and CDCLs and may explain why only this motif is conserved in the CDCLs. Hence, these studies identify a critical component of the sensor involved in initiating the prepore-to-pore transition in the CDCs, which is conserved in a large and diverse group of distant relatives of the CDCs.IMPORTANCE The cholesterol-dependent cytolysins' pore-forming mechanism relies on the ability to sense the completion of the oligomeric prepore structure and initiate the insertion of the β-barrel pore from the assembled prepore structure. These studies show that a conserved motif is an important component of the sensor that triggers the prepore-to-pore transition and that it is conserved in a large family of previously unidentified CDC-like proteins, the genes for which are present in a vast array of microbial species that span most terrestrial environments, as well as most animal and human microbiomes. These studies establish the foundation for future investigations that will probe the contribution of this large family of CDC-like proteins to microbial survival and human disease.
journal_name
mBiojournal_title
mBioauthors
Evans JC,Johnstone BA,Lawrence SL,Morton CJ,Christie MP,Parker MW,Tweten RKdoi
10.1128/mBio.02351-20subject
Has Abstractpub_date
2020-09-29 00:00:00issue
5issn
2150-7511pii
mBio.02351-20journal_volume
11pub_type
杂志文章相关文献
mBio文献大全abstract::Peptides that are synthesized independently of the ribosome in plants, fungi, and bacteria can have clinically relevant anticancer, antihemochromatosis, and antiviral activities, among many other. Despite their natural origin, discovering new natural products is challenging, and there is a need to expand the chemical ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01474-17
更新日期:2017-10-10 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:UNLABELLED:The acquisition, delivery, and incorporation of metals into their respective metalloproteins are important cellular processes. These processes are tightly controlled in order to prevent exposure of cells to free-metal concentrations that could yield oxidative damage. Copper (Cu) is one such metal that is req...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00293-11
更新日期:2012-01-31 00:00:00
abstract::Arthritogenic alphaviruses such as Ross River and Chikungunya viruses cause debilitating muscle and joint pain and pose significant challenges in the light of recent outbreaks. How host immune responses are orchestrated after alphaviral infections and lead to musculoskeletal inflammation remains poorly understood. Her...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.03353-19
更新日期:2020-03-03 00:00:00
abstract:UNLABELLED:Methicillin-resistant Staphylococcus aureus (MRSA) is a global human health problem causing infections in both hospitals and the community. Companion animals, such as cats, dogs, and horses, are also frequently colonized by MRSA and can become infected. We sequenced the genomes of 46 multilocus sequence type...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00985-13
更新日期:2014-05-13 00:00:00
abstract::Motility is an important virulence trait for many bacterial pathogens, allowing them to position themselves in appropriate locations at appropriate times. The motility structures type IV pili and flagella are also involved in sensing surface contact, which modulates pathogenicity. In Pseudomonas aeruginosa, the PilS-P...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01310-18
更新日期:2018-07-24 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::Recent studies have greatly extended our understanding of the microbiota present in and on the human body. Here, advanced sequencing strategies have provided unprecedented analytical power. The important implications that the emerging data have for human health emphasize the need to intensify research in this area (D....
journal_title:mBio
pub_type: 评论,杂志文章
doi:10.1128/mBio.00408-12
更新日期:2012-11-06 00:00:00
abstract::Aspergillosis associated with azole-resistant Aspergillus fumigatus has a mortality rate that can approach 90% in certain patient populations. The best-understood avenue for azole resistance involves changes in the cyp51A gene that encodes the target of azole drugs, lanosterol α-14 demethylase. The most common azole r...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02563-18
更新日期:2019-03-12 00:00:00
abstract:UNLABELLED:The aerial surfaces of plants, or phyllosphere, are microbial habitats important to plant and human health. In order to accurately investigate microbial interactions in the phyllosphere under laboratory conditions, the composition of the phyllosphere microbiota should be representative of the diversity of mi...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01564-14
更新日期:2014-08-12 00:00:00
abstract:UNLABELLED:Enoyl-acyl carrier protein (enoyl-ACP) reductase catalyzes the last step of the elongation cycle in the synthesis of bacterial fatty acids. The Enterococcus faecalis genome contains two genes annotated as enoyl-ACP reductases, a FabI-type enoyl-ACP reductase and a FabK-type enoyl-ACP reductase. We report tha...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00613-13
更新日期:2013-10-01 00:00:00
abstract::Burkholderia pseudomallei, the founding member of the B. pseudomallei complex (Bpc), is a biothreat agent and causes melioidosis, a disease whose treatment mainly relies on ceftazidime and meropenem. The concern is that B. pseudomallei could enhance its drug resistance repertoire by the acquisition of DNA from resista...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00592-20
更新日期:2020-04-14 00:00:00
abstract::The ability to withstand UV damage shapes the ecology of microbes. While mechanisms of UV tolerance were extensively investigated in microorganisms regularly exposed to the sun, far less is known about UV repair of soilborne microorganisms. Fusarium oxysporum is a soilborne fungal plant pathogen that is resistant to U...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02623-19
更新日期:2019-12-03 00:00:00
abstract::Nonflagellar type III secretion systems (nf T3SSs) form a cell surface needle-like structure and an associated translocon that deliver bacterial effector proteins into eukaryotic host cells. This involves a tightly regulated hierarchy of protein secretion. A switch involving SctP and SctU stops secretion of the needle...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01149-18
更新日期:2018-10-02 00:00:00
abstract::ZipA is an essential cell division protein in Escherichia coli Together with FtsA, ZipA tethers dynamic polymers of FtsZ to the cytoplasmic membrane, and these polymers are required to guide synthesis of the cell division septum. This dynamic behavior of FtsZ has been reconstituted on planar lipid surfaces in vitro, v...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01008-18
更新日期:2018-06-19 00:00:00
abstract::Nicotine, a toxic and addictive alkaloid from tobacco, is an environmental pollutant in areas near cigarette production facilities. Over the last decade, our group has studied, in depth, the pyrrolidine pathway of nicotine degradation in Pseudomonas putida S16. However, little is known regarding whole mechanism(s) reg...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00602-19
更新日期:2019-06-04 00:00:00
abstract:UNLABELLED:Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population; in a subset of this population, its presence is associated with development of severe disease, such as gastric cancer. Genomic analysis of several strains has revealed an extensive H. pylori pan-genome, like...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00239-11
更新日期:2011-11-15 00:00:00
abstract:UNLABELLED:In the context of deciphering the metabolic strategies of the obligate pathogenic fungi in the genus Pneumocystis, the genomes of three species (P. carinii, P. murina, and P. jirovecii) were compared among themselves and with the free-living, phylogenetically related fission yeast (Schizosaccharomyces pombe)...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01834-14
更新日期:2014-11-04 00:00:00
abstract::The biosynthesis of antioxidant pigments, namely, betalains, was believed to be restricted to Caryophyllales plants. This paper changes this paradigm, and enzyme mining from bacterial hosts promoted the discovery of bacterial cultures producing betalains. The spectrum of possible sources of betalain pigments in nature...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00345-19
更新日期:2019-03-19 00:00:00
abstract::The fungus Paracoccidioides is a prevalent human pathogen endemic to South America. The genus is composed of five species. In this report, we use 37 whole-genome sequences to study the allocation of genetic variation in Paracoccidioides We tested three genome-wide predictions of advanced speciation, namely, that all s...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01999-20
更新日期:2020-12-22 00:00:00
abstract:UNLABELLED:A mechanistic understanding of the determination and maintenance of the simplest bacterial cell shape, a sphere, remains elusive compared with that of more complex shapes. Cocci seem to lack a dedicated elongation machinery, and a spherical shape has been considered an evolutionary dead-end morphology, as a ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00908-16
更新日期:2016-09-06 00:00:00
abstract::The yeast Yarrowia lipolytica is a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis in Y...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00857-17
更新日期:2017-06-20 00:00:00
abstract::During 2015 to 2016, Brazil reported more Zika virus (ZIKV) cases than any other country, yet population exposure remains unknown. Serological studies of ZIKV are hampered by cross-reactive immune responses against heterologous viruses. We conducted serosurveys for ZIKV, dengue virus (DENV), and Chikungunya virus (CHI...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01390-17
更新日期:2017-11-14 00:00:00
abstract::Enteroaggregative Escherichia coli (EAEC) is an important diarrheal pathogen and a cause of both acute and chronic diarrhea. It is a common cause of pediatric bacterial diarrhea in developing countries. Despite its discovery in 1987, the intestinal tropism of the pathogen remains unknown. Cell lines used to study EAEC...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02419-17
更新日期:2018-02-20 00:00:00
abstract::Systemic infections of Candida species pose a significant threat to public health. Toxicity associated with current therapies and emergence of resistant strains present major therapeutic challenges. Here, we report exploitation of the probiotic properties of two novel, food-derived yeasts, Saccharomyces cerevisiae (st...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02307-19
更新日期:2019-10-15 00:00:00
abstract::Increasing evidence has indicated that single nucleotide polymorphisms (SNPs) are related to the susceptibility of sepsis and might provide potential evidence for the mechanisms of sepsis. Our recent preliminary study showed that the ADAM10 genetic polymorphism was clinically associated with the development of sepsis,...
journal_title:mBio
pub_type: 杂志文章,多中心研究
doi:10.1128/mBio.01663-19
更新日期:2019-08-06 00:00:00
abstract:UNLABELLED:Glycoside hydrolases (GHs) are key enzymes in the depolymerization of plant-derived cellulose, a process central to the global carbon cycle and the conversion of plant biomass to fuels and chemicals. A limited number of GH families hydrolyze crystalline cellulose, often by a processive mechanism along the ce...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01106-16
更新日期:2016-08-23 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::Adult Drosophila melanogaster raised in the absence of symbiotic bacteria have fewer intestinal stem cell divisions and a longer life span than their conventionally reared counterparts. However, we do not know if increased stem cell divisions are essential for symbiont-dependent regulation of longevity. To determine i...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01114-18
更新日期:2018-07-31 00:00:00
abstract::Forested ecosystems throughout the world are experiencing increases in the incidence and magnitude of insect-induced tree mortality with large ecologic ramifications. Interestingly, correlations between water quality and the extent of tree mortality in Colorado montane ecosystems suggest compensatory effects from adja...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01305-17
更新日期:2017-12-05 00:00:00