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 protein. The gatekeeper protein SctW is required for secretion of translocon proteins and controls a second switch to start effector secretion. Salmonella enterica serovar Typhimurium encodes two T3SSs in Salmonella pathogenicity island 1 (SPI-1) and SPI-2. The acidic vacuole containing intracellular bacteria stimulates assembly of the SPI-2 T3SS and its translocon. Sensing the nearly neutral host cytosolic pH is required for effector translocation. Here, we investigated the involvement of SPI-2-encoded proteins SsaP (SctP), SsaU (SctU), SsaV (SctV), and SsaL (SctW) in regulation of secretion. We found that SsaP and SsaU are involved in the first but not the second secretion switch. A random-mutagenesis screen identified amino acids of SsaV that regulate translocon and effector secretion. Single substitutions in subdomain 4 of SsaV or InvA (SPI-1-encoded SctV) phenocopied mutations of their corresponding gatekeepers with respect to translocon and effector protein secretion and host cell interactions. SsaL interacted with SsaV in bacteria exposed to low ambient pH but not after the pH was raised to 7.2. We propose that SsaP and SsaU enable the apparatus to become competent for a secretion switch and facilitate the SsaL-SsaV interaction. This mediates secretion of translocon proteins until neutral pH is sensed, which causes their dissociation, resulting in arrest of translocon secretion and derepression of effector translocation.IMPORTANCESalmonella Typhimurium is an intracellular pathogen that uses the SPI-2 type III secretion system to deliver virulence proteins across the vacuole membrane surrounding intracellular bacteria. This involves a tightly regulated hierarchy of protein secretion controlled by two molecular switches. We found that SPI-2-encoded proteins SsaP and SsaU are involved in the first but not the second secretion switch. We identify key amino acids of the inner membrane protein SsaV that are required to interact with the so-called gatekeeper protein SsaL and show that the dissociation of SsaV-SsaL causes the second switch, leading to delivery of effector proteins. Our results provide insights into the molecular events controlling virulence-associated type III secretion and suggest a broader model describing how the process is regulated.
journal_name
mBiojournal_title
mBioauthors
Yu XJ,Grabe GJ,Liu M,Mota LJ,Holden DWdoi
10.1128/mBio.01149-18subject
Has Abstractpub_date
2018-10-02 00:00:00issue
5issn
2150-7511pii
mBio.01149-18journal_volume
9pub_type
杂志文章相关文献
mBio文献大全abstract::Many viruses produce protein-coding and noncoding subgenomic RNAs (sgRNAs) that are critical for infection. A recently discovered pathway for viral sgRNA production uses exoribonuclease-resistant RNAs (xrRNAs), discrete folded RNA elements that block the processive exoribonucleolytic degradation of RNA. xrRNAs are wid...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02461-18
更新日期:2018-12-18 00:00:00
abstract::Flavor production in yeast fermentation is of paramount importance for industrial production of alcoholic beverages. Although major enzymes of flavor compound biosynthesis have been identified, few specific mutations responsible for strain diversity in flavor production are known. The ATF1-encoded alcohol acetyl coenz...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01279-18
更新日期:2018-08-28 00:00:00
abstract::Mitochondrial function adapts to cellular demands and is affected by the ability of the organelle to undergo fusion and fission in response to physiological and nonphysiological cues. We previously showed that infection with the human bacterial pathogen Listeria monocytogenes elicits transient mitochondrial fission an...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.03171-19
更新日期:2020-02-04 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::Cerebral malaria is a severe neurological complication associated with sequestration of Plasmodium falciparum-infected erythrocytes (IE) in the brain microvasculature, but the specific binding interactions remain under debate. Here, we have generated an engineered three-dimensional (3D) human brain endothelial microve...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00420-19
更新日期:2019-05-28 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::Avian influenza viruses (AIVs) must acquire mammalian-adaptive mutations before they can efficiently replicate in and transmit among humans. The PB2 E627K mutation is known to play a prominent role in the mammalian adaptation of AIVs. The H7N9 AIVs that emerged in 2013 in China easily acquired the PB2 E627K mutation u...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01162-19
更新日期:2019-06-18 00:00:00
abstract::Sinorhizobium meliloti is an alphaproteobacterium belonging to the Rhizobiales Bacteria from this order elongate their cell wall at the new cell pole, generated by cell division. Screening for protein interaction partners of the previously characterized polar growth factors RgsP and RgsM, we identified the inner membr...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00306-20
更新日期:2020-06-30 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) Tat binds the viral RNA structure transactivation-responsive element (TAR) and recruits transcriptional cofactors, amplifying viral mRNA expression. The Tat inhibitor didehydro-cortistatin A (dCA) promotes a state of persistent latency, refractory to viral reactivation. Here...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01750-18
更新日期:2019-07-02 00:00:00
abstract:UNLABELLED:Large-scale rearrangements may be important in evolution because they can alter chromosome organization and gene expression in ways not possible through point mutations. In a long-term evolution experiment, twelve Escherichia coli populations have been propagated in a glucose-limited environment for over 25 ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01377-14
更新日期:2014-09-09 00:00:00
abstract::The 1977-1978 influenza epidemic was probably not a natural event, as the genetic sequence of the virus was nearly identical to the sequences of decades-old strains. While there are several hypotheses that could explain its origin, the possibility that the 1977 epidemic resulted from a laboratory accident has recently...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01013-15
更新日期:2015-08-18 00:00:00
abstract:UNLABELLED:While research has identified an important contribution for metals, such as iron, in microbial pathogenesis, the roles of other transition metals, such as copper, remain mostly unknown. Recent evidence points to a requirement for copper homeostasis in the virulence of Cryptococcus neoformans based on a role ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00285-12
更新日期:2012-10-02 00:00:00
abstract:UNLABELLED:The ability to cultivate food is an innovation that has produced some of the most successful ecological strategies on the planet. Although most well recognized in humans, where agriculture represents a defining feature of civilization, species of ants, beetles, and termites have also independently evolved sy...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02077-14
更新日期:2014-11-18 00:00:00
abstract:UNLABELLED:Pseudomonas aeruginosa is a common cause of infection in the lungs of patients with cystic fibrosis (CF). In addition, biofilm formation and antibiotic resistance of Pseudomonas are major problems that can complicate antibiotic therapy. We evaluated the efficacy of using bacteriophages to kill the pathogen i...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00029-12
更新日期:2012-03-06 00:00:00
abstract:UNLABELLED:The world is at the precipice of a postantibiotic era in which medical procedures and minor injuries can result in bacterial infections that are no longer effectively treated by antibiotics. Cathelicidins are peptides produced by animals to combat bacterial infections and to regulate innate immune responses....
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01418-16
更新日期:2016-09-20 00:00:00
abstract::The PCNA (proliferating cell nuclear antigen) ring plays central roles during DNA replication and repair. The yeast Elg1 RFC-like complex (RLC) is the principal unloader of chromatin-bound PCNA and thus plays a central role in maintaining genome stability. Here we identify a role for Elg1 in the unloading of PCNA duri...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01159-19
更新日期:2019-06-11 00:00:00
abstract:UNLABELLED:Susceptibility to mouse adenovirus type 1 (MAV-1) is mouse strain dependent; susceptible mice die from hemorrhagic encephalomyelitis. The MAV-1 susceptibility quantitative trait locus Msq1 accounts for ~40% of the phenotypic (brain viral load) variance that occurs between resistant BALB/c and susceptible SJL...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00131-12
更新日期:2012-05-29 00:00:00
abstract::The growing ubiquity of electronic devices is increasingly consuming substantial energy and rare resources for materials fabrication, as well as creating expansive volumes of toxic waste. This is not sustainable. Electronic biological materials (e-biologics) that are produced with microbes, or designed with microbial ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00695-17
更新日期:2017-06-27 00:00:00
abstract:UNLABELLED:Type III secretion systems (T3SS) translocate effector proteins into target cells in order to disrupt or modulate host cell signaling pathways and establish replicative niches. However, recognition of T3SS activity by cytosolic pattern recognition receptors (PRRs) of the nucleotide-binding domain leucine ric...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02095-14
更新日期:2015-02-17 00:00:00
abstract::Our current understanding of lipoprotein synthesis and localization in Gram-negative bacteria is based primarily on studies of Escherichia coli Newly synthesized E. coli prolipoproteins undergo posttranslational modifications catalyzed by three essential enzymes (Lgt, LspA, and Lnt). The mature lipoproteins are then s...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00911-20
更新日期:2020-05-19 00:00:00
abstract:UNLABELLED:Enteropathogenic Escherichia coli (EPEC) has the ability to antagonize host apoptosis during infection through promotion and inhibition of effectors injected by the type III secretion system (T3SS), but the total number of these effectors and the overall functional relationships between these effectors durin...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00479-16
更新日期:2016-06-21 00:00:00
abstract:UNLABELLED:The nucleus has emerged as a key target for nucleomodulins, a family of effectors produced by bacterial pathogens to control host transcription or other nuclear processes. The virulence factor LntA from Listeria monocytogenes stimulates interferon responses during infection by inhibiting BAHD1, a nuclear pro...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00775-13
更新日期:2014-01-21 00:00:00
abstract:UNLABELLED:The protein YfeX from Escherichia coli has been proposed to be essential for the process of iron removal from heme by carrying out a dechelation of heme without cleavage of the porphyrin macrocycle. Since this proposed reaction is unique and would represent the first instance of the biological dechelation of...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00248-11
更新日期:2011-11-08 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:Salmonella enterica serovar Typhimurium is one of the most common S. enterica serovars associated with U.S. foodborne outbreaks. S. Typhimurium bacteria isolated from humans exhibit wide-ranging virulence phenotypes in inbred mice, leading to speculation that some strains are more virulent in nature. However...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00154-16
更新日期:2016-03-08 00:00:00
abstract:UNLABELLED:We studied the flocculation mechanism at the molecular level by determining the atomic structures of N-Flo1p and N-Lg-Flo1p in complex with their ligands. We show that they have similar ligand binding mechanisms but distinct carbohydrate specificities and affinities, which are determined by the compactness o...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00427-15
更新日期:2015-04-14 00:00:00
abstract::In bacteria, elongation factor Tu is a translational cofactor that forms ternary complexes with aminoacyl-tRNA (aa-tRNA) and GTP. Binding of a ternary complex to one of four flexible L7/L12 units on the ribosome tethers a charged tRNA in close proximity to the ribosomal A site. Two sequential tests for a match between...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02143-17
更新日期:2018-01-16 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::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::Influenza virus hemagglutinin (HA) surface glycoprotein is currently the primary target of licensed influenza vaccines. Recently, broadly reactive antibodies that target the stalk region of the HA have become a major focus of current novel vaccine development. These antibodies have been observed in humans after natura...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02284-17
更新日期:2018-01-23 00:00:00