Abstract:
UNLABELLED:The Pseudomonas aeruginosa type III secretion system has been associated with poor outcomes in both animal models and human patients. Despite a large number of studies exploring the regulation of type III secretion in vitro, little is known about the timing of secretion during mammalian infection. Here we demonstrate that the exoU gene, which encodes the highly cytotoxic type III effector ExoU, is induced early during acute P. aeruginosa pneumonia. Immunofluorescence microscopy indicated that the amount of ExoU protein in the lung also increased over time. The importance of early expression was examined using a strain of P. aeruginosa with inducible production of ExoU. Delays in expression as short as 3 h led to reduced bacterial burdens in the lungs of mice and improved survival. Our results demonstrate that early expression of exoU is critical to bacterial survival during pneumonia and suggest that therapeutic interventions that delay ExoU secretion for even short periods of time may be efficacious. IMPORTANCE:Pseudomonas aeruginosa is a major contributor to the large numbers of health care-associated infections occurring annually, particularly for immunocompromised patients. Although this organism possesses many virulence factors, the type III secretion system plays an especially important role in both animal models and humans. This system forms a needle-like apparatus that injects toxins directly into eukaryotic cells. The most toxic protein secreted by this molecular machine is ExoU, which causes rapid cell death. In this study, we demonstrated that exoU was expressed and ExoU was produced early during acute pneumonia in a mouse model. Delaying expression of exoU by as little as 3 h enhanced clearance of bacteria and survival of infected mice. Our findings highlight the importance of understanding the regulation of virulence factor expression during infection when designing therapeutic strategies to inhibit the toxic effects of these proteins.
journal_name
mBiojournal_title
mBioauthors
Howell HA,Logan LK,Hauser ARdoi
10.1128/mBio.00032-13subject
Has Abstractpub_date
2013-03-12 00:00:00pages
e00032-13issue
2issn
2150-7511pii
mBio.00032-13journal_volume
4pub_type
杂志文章相关文献
mBio文献大全abstract::Epstein-Barr virus (EBV) infects and activates resting human B lymphocytes, reprograms them, induces their proliferation, and establishes a latent infection in them. In established EBV-infected cell lines, many viral latent genes are expressed. Their roles in supporting the continuous proliferation of EBV-infected B c...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01723-19
更新日期:2019-09-17 00:00:00
abstract:UNLABELLED:Acinetobacter baumannii is a nosocomial pathogen of increasing importance due to its multiple resistance to antibiotics and ability to survive in the hospital environment linked to its capacity to form biofilms. To fully characterize the contribution of AdeABC, AdeFGH, and AdeIJK resistance-nodulation-cell d...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00309-15
更新日期:2015-03-24 00:00:00
abstract::Stenotrophomonas maltophilia is a Gram-negative, nonfermenting, environmental bacillus that is an important cause of nosocomial infections, primarily associated with the respiratory tract in the immunocompromised population. Aiming to understand the population structure, microbiological characteristics and impact of a...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00405-19
更新日期:2019-07-02 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::During DNA replication, stalling can occur when the replicative DNA polymerases encounter lesions or hard-to replicate regions. Under these circumstances, the processivity factor PCNA gets ubiquitylated at lysine 164, inducing the DNA damage tolerance (DDT) mechanisms that can bypass lesions encountered during DNA rep...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00705-20
更新日期:2020-05-05 00:00:00
abstract::Staphylococcus aureus is intrinsically resistant to polymyxins (polymyxin B and colistin), an important class of cationic antimicrobial peptides used in treatment of Gram-negative bacterial infections. To understand the mechanisms underlying intrinsic polymyxin resistance in S. aureus, we screened the Nebraska Transpo...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01114-17
更新日期:2017-09-05 00:00:00
abstract::Lassa virus (LASV) infection is a major public health concern due to high fatality rates and limited effective treatment. The interferon-stimulated gene cholesterol 25-hydroxylase (CH25H) encodes an enzyme that catalyzes the production of 25-hydroxycholesterol (25HC). 25HC is involved in regulating cholesterol biosynt...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01808-16
更新日期:2016-12-20 00:00:00
abstract:UNLABELLED:Coagulase (Coa) and Efb, secreted Staphylococcus aureus proteins, are important virulence factors in staphylococcal infections. Coa interacts with fibrinogen (Fg) and induces the formation of fibrin(ogen) clots through activation of prothrombin. Efb attracts Fg to the bacterial surface and forms a shield to ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01885-15
更新日期:2016-01-05 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::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 Mo- and V-nitrogenases are two homologous members of the nitrogenase family that are distinguished mainly by the presence of different heterometals (Mo or V) at their respective cofactor sites (M- or V-cluster). However, the V-nitrogenase is ~600-fold more active than its Mo counterpart in reducing CO to hydrocarb...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00310-18
更新日期:2018-03-13 00:00:00
abstract:UNLABELLED:Human cathepsin W (CtsW) is a cysteine protease, which was identified in a genome-wide RNA interference (RNAi) screen to be required for influenza A virus (IAV) replication. In this study, we show that reducing the levels of expression of CtsW reduces viral titers for different subtypes of IAV, and we map th...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00297-15
更新日期:2015-06-09 00:00:00
abstract::Dephospho-coenzyme A (dephospho-CoA) kinase (DPCK) catalyzes the ATP-dependent phosphorylation of dephospho-CoA, the final step in coenzyme A (CoA) biosynthesis. DPCK has been identified and characterized in bacteria and eukaryotes but not in archaea. The hyperthermophilic archaeon Thermococcus kodakarensis encodes tw...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01146-19
更新日期:2019-07-23 00:00:00
abstract::A central question in mechanobiology is how cellular-scale structures are established and regulated. In bacteria, the cell envelope is essential for mechanical integrity, protecting against environmental stresses and bearing the load from high turgor pressures. Trivedi et al. (mBio 9:e01340-18, 2018, https://doi.org/1...
journal_title:mBio
pub_type: 评论,杂志文章
doi:10.1128/mBio.02127-18
更新日期:2018-10-23 00:00:00
abstract::Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YF...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00819-17
更新日期:2017-08-15 00:00:00
abstract:UNLABELLED:The promoter most strongly induced upon activation of the Cpx two-component envelope stress response is the cpxP promoter. The 3' untranscribed region (UTR) of the cpxP transcript is shown to produce a small RNA (sRNA), CpxQ. We investigated the role of CpxQ in combating envelope stress. Remarkably, the two ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00312-16
更新日期:2016-04-05 00:00:00
abstract::Inhibition of apoptotic death of macrophages by Mycobacterium tuberculosis represents an important mechanism of virulence that results in pathogen survival both in vitro and in vivo. To identify M. tuberculosis virulence determinants involved in the modulation of apoptosis, we previously screened a transposon bank of ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01278-14
更新日期:2014-08-19 00:00:00
abstract::The development of vaccines is one of the greatest medical interventions in the history of global infectious diseases and has contributed to the annual saving of at least 2 to 3 million lives worldwide. However, many diseases are not preventable through currently available vaccines, and the potential of modulating the...
journal_title:mBio
pub_type: 杂志文章,评审
doi:10.1128/mBio.02616-20
更新日期:2020-12-22 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::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::Photosynthetic bacteria are capable of producing their own food via photosynthesis. Unsurprisingly, they evolved the ability to move toward better light conditions (i.e., phototaxis). In a recent article in mBio, Chau et al. tuned the wavelength, flux, direction, and timing of light input and characterized the motilit...
journal_title:mBio
pub_type: 评论,杂志文章
doi:10.1128/mBio.00498-17
更新日期:2017-04-11 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::Plasmodium vivax causes heavy burdens of disease across malarious regions worldwide. Mature P. vivax asexual and transmissive gametocyte stages occur in the blood circulation, and it is often assumed that accumulation/sequestration in tissues is not an important phase in their development. Here, we present a systemati...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00625-18
更新日期:2018-05-08 00:00:00
abstract::Uncultured and therefore uncharacterized Bacteroidetes lineages are ubiquitous in many natural ecosystems which specialize in lignocellulose degradation. However, their metabolic contribution remains mysterious, as well-studied cultured Bacteroidetes have been shown to degrade only soluble polysaccharides within the h...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01401-14
更新日期:2014-08-05 00:00:00
abstract::The proteasome is a major protein degradation machinery with essential and diverse biological functions. Upon induction by cytokines, proteasome subunits β1, β2, and β5 are replaced by β1i/LMP2, β2i/MECL-1, and β5i/LMP7, resulting in the formation of an immunoproteasome (iProteasome). iProteasome-degraded products are...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02221-19
更新日期:2020-10-27 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
abstract:UNLABELLED:The intracellular parasite Toxoplasma gondii infects a wide variety of vertebrate species globally. Infection in most hosts causes a lifelong chronic infection and generates immunological memory responses that protect the host against new infections. In regions where the organism is endemic, multiple exposur...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02280-14
更新日期:2015-02-24 00:00:00
abstract:UNLABELLED:Similar to many eukaryotic viruses (and unlike bacteriophages), viruses infecting archaea are often encased in lipid-containing envelopes. However, the mechanisms of their morphogenesis and egress remain unexplored. Here, we used dual-axis electron tomography (ET) to characterize the morphogenesis of Sulfolo...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01439-16
更新日期:2016-09-13 00:00:00
abstract::Unlike all other archaeal lineages, ammonia-oxidizing archaea (AOA) of the phylum Thaumarchaeota are widespread and abundant in all moderate and oxic environments on Earth. The evolutionary adaptations that led to such unprecedented ecological success of a microbial clade characterized by highly conserved energy and c...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02371-20
更新日期:2020-10-13 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