Abstract:
:Most fungal pathogens of humans display robust protective oxidative stress responses that contribute to their pathogenicity. The induction of enzymes that detoxify reactive oxygen species (ROS) is an essential component of these responses. We showed previously that ectopic expression of the heme-containing catalase enzyme in Candida albicans enhances resistance to oxidative stress, combinatorial oxidative plus cationic stress, and phagocytic killing. Clearly ectopic catalase expression confers fitness advantages in the presence of stress, and therefore in this study we tested whether it enhances fitness in the absence of stress. We addressed this using a set of congenic barcoded C. albicans strains that include doxycycline-conditional tetON-CAT1 expressors. We show that high basal catalase levels, rather than CAT1 induction following stress imposition, reduce ROS accumulation and cell death, thereby promoting resistance to acute peroxide or combinatorial stress. This conclusion is reinforced by our analyses of phenotypically diverse clinical isolates and the impact of stochastic variation in catalase expression upon stress resistance in genetically homogeneous C. albicans populations. Accordingly, cat1Δ cells are more sensitive to neutrophil killing. However, we find that catalase inactivation does not attenuate C. albicans virulence in mouse or invertebrate models of systemic candidiasis. Furthermore, our direct comparisons of fitness in vitro using isogenic barcoded CAT1, cat1Δ and tetON-CAT1 strains show that, while ectopic catalase expression confers a fitness advantage during peroxide stress, it confers a fitness defect in the absence of stress. This fitness defect is suppressed by iron supplementation. Also high basal catalase levels induce key iron assimilatory functions (CFL5, FET3, FRP1, FTR1). We conclude that while high basal catalase levels enhance peroxide stress resistance, they place pressure on iron homeostasis through an elevated cellular demand for iron, thereby reducing the fitness of C. albicans in iron-limiting tissues within the host.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Pradhan A,Herrero-de-Dios C,Belmonte R,Budge S,Lopez Garcia A,Kolmogorova A,Lee KK,Martin BD,Ribeiro A,Bebes A,Yuecel R,Gow NAR,Munro CA,MacCallum DM,Quinn J,Brown AJPdoi
10.1371/journal.ppat.1006405subject
Has Abstractpub_date
2017-05-22 00:00:00pages
e1006405issue
5eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-16-02888journal_volume
13pub_type
杂志文章相关文献
PLoS Pathogens文献大全abstract::The unfolded protein response (UPR) in the endoplasmic reticulum (ER) constitutes a critical component of host innate immunity against microbial infections. In this report, we show that porcine reproductive and respiratory syndrome virus (PRRSV) utilizes the UPR machinery for its own benefit. We provide evidence that ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008169
更新日期:2019-11-18 00:00:00
abstract::The success of Mycobacterium tuberculosis as a pathogen derives from its facile adaptation to the intracellular milieu of human macrophages. To explore this process, we asked whether adaptation also required interference with the metabolic machinery of the host cell. Temporal profiling of the metabolic flux, in cells ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004265
更新日期:2014-07-24 00:00:00
abstract::Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005111
更新日期:2015-08-24 00:00:00
abstract::Paramyxoviruses are known to replicate in the cytoplasm and bud from the plasma membrane. Matrix is the major structural protein in paramyxoviruses that mediates viral assembly and budding. Curiously, the matrix proteins of a few paramyxoviruses have been found in the nucleus, although the biological function associat...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1001186
更新日期:2010-11-11 00:00:00
abstract::Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [P...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003211
更新日期:2013-03-01 00:00:00
abstract::The Venus kinase receptor (VKR) is a single transmembrane molecule composed of an intracellular tyrosine kinase domain close to that of insulin receptor and an extracellular Venus Flytrap (VFT) structure similar to the ligand binding domain of many class C G protein coupled receptors. This receptor tyrosine kinase (RT...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004138
更新日期:2014-05-29 00:00:00
abstract::Endemic Burkitt's lymphoma (eBL) arises from the germinal center (GC). It is a common tumor of young children in tropical Africa and its occurrence is closely linked geographically with the incidence of P. falciparum malaria. This association was noted more than 50 years ago. Since then we have learned that eBL contai...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004170
更新日期:2014-05-29 00:00:00
abstract::Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibit...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000287
更新日期:2009-02-01 00:00:00
abstract::Measles is characterized by fever and a maculopapular skin rash, which is accompanied by immune clearance of measles virus (MV)-infected cells. Histopathological analyses of skin biopsies from humans and non-human primates (NHPs) with measles rash have identified MV-infected keratinocytes and mononuclear cells in the ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008253
更新日期:2020-10-08 00:00:00
abstract::Entamoeba histolytica transmembrane kinases (EhTMKs) can be grouped into six distinct families on the basis of motifs and sequences. Analysis of the E. histolytica genome revealed the presence of 35 EhTMKB1 members on the basis of sequence identity (>or=95%). Only six homologs were full length containing an extracellu...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000929
更新日期:2010-06-03 00:00:00
abstract::Unique purine-rich mRNA sequences embedded in the coding sequences of a distinct group of gammaherpesvirus maintenance proteins underlie the ability of the latently infected cell to minimize immune recognition. The Epstein-Barr virus nuclear antigen, EBNA1, a well characterized lymphocryptovirus maintenance protein ha...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003112
更新日期:2012-12-01 00:00:00
abstract::The repeat region of the Plasmodium falciparum circumsporozoite protein (CSP) is a major vaccine antigen because it can be targeted by parasite neutralizing antibodies; however, little is known about this interaction. We used isothermal titration calorimetry, X-ray crystallography and mutagenesis-validated modeling to...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006469
更新日期:2017-07-31 00:00:00
abstract::The cytidine deaminases APOBEC3G and APOBEC3F exert anti-HIV-1 activity that is countered by the HIV-1 vif protein. Based on potential transcription factor binding sites in their putative promoters, we hypothesized that expression of APOBEC3G and APOBEC3F would vary with T helper lymphocyte differentiation. Naive CD4+...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000292
更新日期:2009-02-01 00:00:00
abstract::Newcastle Disease Virus (NDV) is a pathogenic strain of avian paramyxovirus (aPMV-1) that is among the most serious of disease threats to the poultry industry worldwide. Viral diversity is high in aPMV-1; eight genotypes are recognized based on phylogenetic reconstruction of gene sequences. Modified live vaccines have...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000872
更新日期:2010-04-22 00:00:00
abstract::Eliciting broad tier 2 neutralizing antibodies (nAbs) is a major goal of HIV-1 vaccine research. Here we investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit nAbs. Unusually potent nAb titers developed in 2 of 8 rabbits immunized with virus-like particles (VLPs) expressing trimers (trimer...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004932
更新日期:2015-05-29 00:00:00
abstract::Members of the major candidate phylum Dependentiae (a.k.a. TM6) are widespread across diverse environments from showerheads to peat bogs; yet, with the exception of two isolates infecting amoebae, they are only known from metagenomic data. The limited knowledge of their biology indicates that they have a long evolutio...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1007801
更新日期:2019-05-31 00:00:00
abstract::We performed a quantitative analysis of the HLA restriction, antigen and epitope specificity of human pathogen specific responses in healthy individuals infected with M. tuberculosis (Mtb), in a South African cohort as a test case. The results estimate the breadth of T cell responses for the first time in the context ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005760
更新日期:2016-07-13 00:00:00
abstract::Fusogenic reoviruses encode fusion-associated small transmembrane (FAST) protein, which induces cell-cell fusion. FAST protein is the only known fusogenic protein in non-enveloped viruses, and its role in virus replication is not yet known. We generated replication-competent, FAST protein-deficient pteropine orthoreov...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1007675
更新日期:2019-04-25 00:00:00
abstract::Highly pathogenic avian H5N1 influenza A viruses have spread throughout Asia, Europe, and Africa, raising serious worldwide concern about their pandemic potential. Although more than 250 people have been infected with these viruses, with a consequent high rate of mortality, the molecular mechanisms responsible for the...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.0030133
更新日期:2007-10-05 00:00:00
abstract::Mycobacterium tuberculosis (Mtb) remains a major public health problem, with an effective vaccine continuing to prove elusive. Progress in vaccination strategies has been hampered by a lack of appreciation of the bacterium's response to dynamic changes in the host immune environment. Here, we utilize reporter Mtb stra...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004394
更新日期:2014-09-18 00:00:00
abstract::The envelope glycoprotein (Env) complexes of the human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate viral entry and are a target for neutralizing antibodies. The receptor binding surfaces of Env are in large part sterically occluded or conformationally masked prior to receptor binding. Knowl...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.0020083
更新日期:2006-08-01 00:00:00
abstract::To ensure their survival, microbial pathogens have evolved diverse strategies to subvert host immune defenses. The human retrovirus HIV-1 has been proposed to hijack the natural endocytic function of dendritic cells (DCs) to infect interacting CD4 T cells in a process termed trans-infection. Although DCs can be direct...
journal_title:PLoS pathogens
pub_type: 杂志文章,评审
doi:10.1371/journal.ppat.1000051
更新日期:2008-06-27 00:00:00
abstract::SIV(mac239) infection of rhesus macaques (RMs) results in AIDS despite the generation of a strong antiviral cytotoxic T lymphocyte (CTL) response, possibly due to the emergence of viral escape mutants that prevent recognition of infected cells by CTLs. To determine the anatomic origin of these SIV mutants, we longitud...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002048
更新日期:2011-05-01 00:00:00
abstract::Septic shock caused by Neisseria meningitidis is typically rapidly evolving and often fatal despite antibiotic therapy. Further understanding of the mechanisms underlying the disease is necessary to reduce fatality rates. Postmortem samples from the characteristic purpuric rashes of the infection show bacterial aggreg...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003139
更新日期:2013-01-01 00:00:00
abstract::Infection with equid herpesvirus type 1 (EHV-1) leads to respiratory disease, abortion, and neurologic disorders in horses. Molecular epidemiology studies have demonstrated that a single nucleotide polymorphism resulting in an amino acid variation of the EHV-1 DNA polymerase (N752/D752) is significantly associated wit...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.0030160
更新日期:2007-11-01 00:00:00
abstract::The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006230
更新日期:2017-02-22 00:00:00
abstract::RNA interference (RNAi) pathways are widespread in metaozoans but the genes required show variable occurrence or activity in eukaryotic microbes, including many pathogens. While some Leishmania lack RNAi activity and Argonaute or Dicer genes, we show that Leishmania braziliensis and other species within the Leishmania...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1001161
更新日期:2010-10-28 00:00:00
abstract::Respiratory virus infections, such as influenza, typically induce a robust type I (pro-inflammatory cytokine) immune response, however, the production of type 2 cytokines has been observed. Type 2 cytokine production during respiratory virus infection is linked to asthma exacerbation; however, type 2 cytokines may als...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003615
更新日期:2013-09-01 00:00:00
abstract::Competence stimulating peptide (CSP) is a 17-amino acid peptide pheromone secreted by Streptococcus pneumoniae. Upon binding of CSP to its membrane-associated receptor kinase ComD, a cascade of signaling events is initiated, leading to activation of the competence regulon by the response regulator ComE. Genes encoding...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002241
更新日期:2011-09-01 00:00:00
abstract::Bacterial bloodstream infections (BSI) are a major health concern and can cause up to 40% mortality. Pseudomonas aeruginosa BSI is often of nosocomial origin and is associated with a particularly poor prognosis. The mechanism of bacterial persistence in blood is still largely unknown. Here, we analyzed the behavior of...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008893
更新日期:2020-12-16 00:00:00