Evolutionary landscape of the Mycobacterium tuberculosis complex from the viewpoint of PhoPR: implications for virulence regulation and application to vaccine development.


:Different members of the Mycobacterium genus have evolved to cause tuberculosis in diverse human populations and in a variety of animal species. Our cumulative knowledge of mycobacterial genomes indicates that mutations in the PhoPR two-component virulence system were acquired not only during the natural evolution of mycobacterial species but also during in vitro subculture, which has given rise to the attenuated reference strain H37Ra or to different daughter strains of Mycobacterium bovis BCG. PhoPR is a well-known regulator of pathogenic phenotypes, including secretion of the virulence factor ESAT-6, biosynthesis of acyltrehalose-based lipids, and modulation of antigen export, in members of the Mycobacterium tuberculosis complex (MTBC). Evolutionarily conserved polymorphisms in PhoPR from Mycobacterium africanum, M. bovis, or M. tuberculosis H37Ra result in loss of functional phenotypes. Interestingly, some members of the MTBC have acquired compensatory mutations to counteract these polymorphisms and, probably, to maintain their pathogenic potential. Some of these compensatory mutations include the insertion of the IS6110 element upstream from phoPR in a particular M. bovis strain that is able to transmit between humans or polymorphisms in M. africanum and M. bovis that affect the regulatory region of the espACD operon, allowing PhoPR-independent ESAT-6 secretion. This review highlights the increasing knowledge of the significance of PhoPR in the evolution of the MTBC and its potential application in the construction of new attenuated vaccines based on phoPR inactivation. In this context, the live attenuated vaccine MTBVAC, based on a phoP fadD26 deletion mutant of M. tuberculosis, is the first vaccine of this kind to successfully enter into clinical development, representing a historic milestone in the field of human vaccinology.






Broset E,Martín C,Gonzalo-Asensio J




Has Abstract


2015-10-20 00:00:00














  • Identification of a Novel Cobamide Remodeling Enzyme in the Beneficial Human Gut Bacterium Akkermansia muciniphila.

    abstract::The beneficial human gut bacterium Akkermansia muciniphila provides metabolites to other members of the gut microbiota by breaking down host mucin, but most of its other metabolic functions have not been investigated. A. muciniphila strain MucT is known to use cobamides, the vitamin B12 family of cofactors with struct...


    pub_type: 杂志文章


    authors: Mok KC,Sokolovskaya OM,Nicolas AM,Hallberg ZF,Deutschbauer A,Carlson HK,Taga ME

    更新日期:2020-12-08 00:00:00

  • Improper Coordination of BamA and BamD Results in Bam Complex Jamming by a Lipoprotein Substrate.

    abstract::The β-barrel assembly machinery, the Bam complex, is central to the biogenesis of integral outer membrane proteins (OMPs) as well as OMP-dependent surface-exposed lipoproteins, such as regulator of capsule synthesis protein F (RcsF). Previous genetic analysis established the model that nonessential components BamE and...


    pub_type: 杂志文章


    authors: Tata M,Konovalova A

    更新日期:2019-05-21 00:00:00

  • The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate.

    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...


    pub_type: 杂志文章


    authors: Rozo M,Gronvall GK

    更新日期:2015-08-18 00:00:00

  • (p)ppGpp and c-di-AMP Homeostasis Is Controlled by CbpB in Listeria monocytogenes.

    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...


    pub_type: 杂志文章


    authors: Peterson BN,Young MKM,Luo S,Wang J,Whiteley AT,Woodward JJ,Tong L,Wang JD,Portnoy DA

    更新日期:2020-08-25 00:00:00

  • Twice-daily application of HIV microbicides alter the vaginal microbiota.

    abstract:UNLABELLED:Vaginal HIV microbicides offer great promise in preventing HIV transmission, but failures of phase 3 clinical trials, in which microbicide-treated subjects had an increased risk of HIV transmission, raised concerns about endpoints used to evaluate microbicide safety. A possible explanation for the increased ...


    pub_type: 杂志文章,随机对照试验


    authors: Ravel J,Gajer P,Fu L,Mauck CK,Koenig SS,Sakamoto J,Motsinger-Reif AA,Doncel GF,Zeichner SL

    更新日期:2012-12-18 00:00:00

  • Population Structure and Genetic Diversity among Isolates of Coccidioides posadasii in Venezuela and Surrounding Regions.

    abstract::Coccidioides posadasii is a pathogenic fungus that causes coccidioidomycosis in many arid regions of the Americas. One of these regions is bordered by the Caribbean Sea, and the surrounding landscape may play an important role in the dispersion of C. posadasii across South America through southeastern Mexico, Honduras...


    pub_type: 杂志文章


    authors: Teixeira MM,Alvarado P,Roe CC,Thompson GR 3rd,Patané JSL,Sahl JW,Keim P,Galgiani JN,Litvintseva AP,Matute DR,Barker BM

    更新日期:2019-11-26 00:00:00

  • Inhibition of the ATP Synthase Eliminates the Intrinsic Resistance of Staphylococcus aureus towards Polymyxins.

    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...


    pub_type: 杂志文章


    authors: Vestergaard M,Nøhr-Meldgaard K,Bojer MS,Krogsgård Nielsen C,Meyer RL,Slavetinsky C,Peschel A,Ingmer H

    更新日期:2017-09-05 00:00:00

  • Silver and Copper Acute Effects on Membrane Proteins and Impact on Photosynthetic and Respiratory Complexes in Bacteria.

    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...


    pub_type: 杂志文章


    authors: Tambosi R,Liotenberg S,Bourbon ML,Steunou AS,Babot M,Durand A,Kebaili N,Ouchane S

    更新日期:2018-11-20 00:00:00

  • Genomic Context of Azole Resistance Mutations in Aspergillus fumigatus Determined Using Whole-Genome Sequencing.

    abstract:UNLABELLED:A rapid and global emergence of azole resistance has been observed in the pathogenic fungus Aspergillus fumigatus over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves mutations in the cyp51A gene, which encodes a protein targeted by triazole antifungal dr...


    pub_type: 杂志文章


    authors: Abdolrasouli A,Rhodes J,Beale MA,Hagen F,Rogers TR,Chowdhary A,Meis JF,Armstrong-James D,Fisher MC

    更新日期:2015-06-02 00:00:00

  • Mechanisms, Detection, and Relevance of Protein Acetylation in Prokaryotes.

    abstract::Posttranslational modification of a protein, either alone or in combination with other modifications, can control properties of that protein, such as enzymatic activity, localization, stability, or interactions with other molecules. N-ε-Lysine acetylation is one such modification that has gained attention in recent ye...


    pub_type: 杂志文章,评审


    authors: Christensen DG,Baumgartner JT,Xie X,Jew KM,Basisty N,Schilling B,Kuhn ML,Wolfe AJ

    更新日期:2019-04-09 00:00:00

  • Simple sari cloth filtration of water is sustainable and continues to protect villagers from cholera in Matlab, Bangladesh.

    abstract::A simple method for filtering water to reduce the incidence of cholera was tested in a field trial in Matlab, Bangladesh, and proved effective. A follow-up study was conducted 5 years later to determine whether the filtration method continued to be employed by villagers and its impact on the incidence of cholera. A to...


    pub_type: 杂志文章


    authors: Huq A,Yunus M,Sohel SS,Bhuiya A,Emch M,Luby SP,Russek-Cohen E,Nair GB,Sack RB,Colwell RR

    更新日期:2010-05-18 00:00:00

  • Identification of Dephospho-Coenzyme A (Dephospho-CoA) Kinase in Thermococcus kodakarensis and Elucidation of the Entire CoA Biosynthesis Pathway in Archaea.

    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...


    pub_type: 杂志文章


    authors: Shimosaka T,Makarova KS,Koonin EV,Atomi H

    更新日期:2019-07-23 00:00:00

  • Repair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width.

    abstract::Membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. Here, we report the first paradigm of Ca2+-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of Photobacterium damselae subsp. damselae In striking contrast, V...


    pub_type: 杂志文章


    authors: von Hoven G,Rivas AJ,Neukirch C,Meyenburg M,Qin Q,Parekh S,Hellmann N,Husmann M

    更新日期:2017-02-14 00:00:00

  • Mouse and Human Monoclonal Antibodies Protect against Infection by Multiple Genotypes of Japanese Encephalitis Virus.

    abstract::Japanese encephalitis virus (JEV) remains a leading cause of viral encephalitis worldwide. Although JEV-specific antibodies have been described, an assessment of their ability to neutralize multiple genotypes of JEV has been limited. Here, we describe the development of a panel of mouse and human neutralizing monoclon...


    pub_type: 杂志文章


    authors: Fernandez E,Kose N,Edeling MA,Adhikari J,Sapparapu G,Lazarte SM,Nelson CA,Govero J,Gross ML,Fremont DH,Crowe JE Jr,Diamond MS

    更新日期:2018-02-27 00:00:00

  • Two KTR Mannosyltransferases Are Responsible for the Biosynthesis of Cell Wall Mannans and Control Polarized Growth in Aspergillus fumigatus.

    abstract::Fungal cell wall mannans are complex carbohydrate polysaccharides with different structures in yeasts and molds. In contrast to yeasts, their biosynthetic pathway has been poorly investigated in filamentous fungi. In Aspergillus fumigatus, the major mannan structure is a galactomannan that is cross-linked to the β-1,3...


    pub_type: 杂志文章


    authors: Henry C,Li J,Danion F,Alcazar-Fuoli L,Mellado E,Beau R,Jouvion G,Latgé JP,Fontaine T

    更新日期:2019-02-12 00:00:00

  • Phyllosphere microbiota composition and microbial community transplantation on lettuce plants grown indoors.

    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...


    pub_type: 杂志文章


    authors: Williams TR,Marco ML

    更新日期:2014-08-12 00:00:00

  • SLC6A14 Is a Genetic Modifier of Cystic Fibrosis That Regulates Pseudomonas aeruginosa Attachment to Human Bronchial Epithelial Cells.

    abstract::Cystic fibrosis (CF) is caused by mutations in the CFTR gene and is associated with progressive and ultimately fatal infectious lung disease. There can be considerable variability in disease severity among individuals with the same CFTR mutations, and recent genome-wide association studies have identified secondary ge...


    pub_type: 杂志文章


    authors: Di Paola M,Park AJ,Ahmadi S,Roach EJ,Wu YS,Struder-Kypke M,Lam JS,Bear CE,Khursigara CM

    更新日期:2017-12-19 00:00:00

  • A Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria.

    abstract::The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in sup...


    pub_type: 杂志文章


    authors: Lori C,Kaczmarczyk A,de Jong I,Jenal U

    更新日期:2018-05-22 00:00:00

  • Petrobactin Is Exported from Bacillus anthracis by the RND-Type Exporter ApeX.

    abstract::Bacillus anthracis-a Gram-positive, spore-forming bacterium-causes anthrax, a highly lethal disease with high bacteremia titers. Such rapid growth requires ample access to nutrients, including iron. However, access to this critical metal is heavily restricted in mammals, which requires B. anthracis to employ petrobact...


    pub_type: 杂志文章


    authors: Hagan AK,Tripathi A,Berger D,Sherman DH,Hanna PC

    更新日期:2017-09-12 00:00:00

  • Salmonella enterica Serovar Typhi in Bangladesh: Exploration of Genomic Diversity and Antimicrobial Resistance.

    abstract::Typhoid fever, caused by Salmonella enterica serovar Typhi, is a global public health concern due to increasing antimicrobial resistance (AMR). Characterization of S Typhi genomes for AMR and the evolution of different lineages, especially in countries where typhoid fever is endemic such as Bangladesh, will help publi...


    pub_type: 杂志文章


    authors: Tanmoy AM,Westeel E,De Bruyne K,Goris J,Rajoharison A,Sajib MSI,van Belkum A,Saha SK,Komurian-Pradel F,Endtz HP

    更新日期:2018-11-13 00:00:00

  • Plasmodium falciparum-infected erythrocyte knob density is linked to the PfEMP1 variant expressed.

    abstract:UNLABELLED:Members of the clonally variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediate adhesion of infected erythrocytes (IEs) to vascular receptors. PfEMP1 expression is normally confined to nanoscale knob protrusions on the IE surface membrane. To investigate the relationship between ...


    pub_type: 杂志文章


    authors: Subramani R,Quadt K,Jeppesen AE,Hempel C,Petersen JE,Hassenkam T,Hviid L,Barfod L

    更新日期:2015-10-06 00:00:00

  • Tol-Pal System and Rgs Proteins Interact to Promote Unipolar Growth and Cell Division in Sinorhizobium meliloti.

    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...


    pub_type: 杂志文章


    authors: Krol E,Yau HCL,Lechner M,Schäper S,Bange G,Vollmer W,Becker A

    更新日期:2020-06-30 00:00:00

  • Identification of Novel Alleles Conferring Superior Production of Rose Flavor Phenylethyl Acetate Using Polygenic Analysis in Yeast.

    abstract::Flavor compound metabolism is one of the last areas in metabolism where multiple genes encoding biosynthetic enzymes are still unknown. A major challenge is the involvement of side activities of enzymes having their main function in other areas of metabolism. We have applied pooled-segregant whole-genome sequence anal...


    pub_type: 杂志文章


    authors: Trindade de Carvalho B,Holt S,Souffriau B,Lopes Brandão R,Foulquié-Moreno MR,Thevelein JM

    更新日期:2017-11-07 00:00:00

  • Humic acid-oxidizing, nitrate-reducing bacteria in agricultural soils.

    abstract:UNLABELLED:This study demonstrates the prevalence, phylogenetic diversity, and physiology of nitrate-reducing microorganisms capable of utilizing reduced humic acids (HA) as electron donors in agricultural soils. Most probable number (MPN) enumeration of agricultural soils revealed large populations (10(4) to 10(6) cel...


    pub_type: 杂志文章


    authors: Van Trump JI,Wrighton KC,Thrash JC,Weber KA,Andersen GL,Coates JD

    更新日期:2011-07-12 00:00:00

  • Stress-Induced MazF-Mediated Proteins in Escherichia coli.

    abstract::Escherichia colimazEF is an extensively studied stress-induced toxin-antitoxin (TA) system. The toxin MazF is an endoribonuclease that cleaves RNAs at ACA sites. By that means, under stress, the induced MazF generates a stress-induced translation machinery (STM) composed of MazF-processed mRNAs and selective ribosomes...


    pub_type: 杂志文章


    authors: Nigam A,Ziv T,Oron-Gottesman A,Engelberg-Kulka H

    更新日期:2019-03-26 00:00:00

  • A New Way of Sensing: Need-Based Activation of Antibiotic Resistance by a Flux-Sensing Mechanism.

    abstract:UNLABELLED:Sensing of and responding to environmental changes are of vital importance for microbial cells. Consequently, bacteria have evolved a plethora of signaling systems that usually sense biochemical cues either via direct ligand binding, thereby acting as "concentration sensors," or by responding to downstream e...


    pub_type: 杂志文章


    authors: Fritz G,Dintner S,Treichel NS,Radeck J,Gerland U,Mascher T,Gebhard S

    更新日期:2015-07-21 00:00:00

  • Petrobactin Protects against Oxidative Stress and Enhances Sporulation Efficiency in Bacillus anthracis Sterne.

    abstract::Bacillus anthracis is a Gram-positive bacillus that under conditions of environmental stress, such as low nutrients, can convert from a vegetative bacillus to a highly durable spore that enables long-term survival. The sporulation process is regulated by a sequential cascade of dedicated transcription factors but requ...


    pub_type: 杂志文章


    authors: Hagan AK,Plotnick YM,Dingle RE,Mendel ZI,Cendrowski SR,Sherman DH,Tripathi A,Hanna PC

    更新日期:2018-11-06 00:00:00

  • Coagulase and Efb of Staphylococcus aureus Have a Common Fibrinogen Binding Motif.

    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 ...


    pub_type: 杂志文章


    authors: Ko YP,Kang M,Ganesh VK,Ravirajan D,Li B,Höök M

    更新日期:2016-01-05 00:00:00

  • Mycobacterial Esx-3 requires multiple components for iron acquisition.

    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...


    pub_type: 杂志文章


    authors: Siegrist MS,Steigedal M,Ahmad R,Mehra A,Dragset MS,Schuster BM,Philips JA,Carr SA,Rubin EJ

    更新日期:2014-05-06 00:00:00

  • Antagonistic Rgg regulators mediate quorum sensing via competitive DNA binding in Streptococcus pyogenes.

    abstract:UNLABELLED:Recent studies have established the fact that multiple members of the Rgg family of transcriptional regulators serve as key components of quorum sensing (QS) pathways that utilize peptides as intercellular signaling molecules. We previously described a novel QS system in Streptococcus pyogenes which utilizes...


    pub_type: 杂志文章


    authors: Lasarre B,Aggarwal C,Federle MJ

    更新日期:2013-01-02 00:00:00