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














  • Avian Influenza Virus PB1 Gene in H3N2 Viruses Evolved in Humans To Reduce Interferon Inhibition by Skewing Codon Usage toward Interferon-Altered tRNA Pools.

    abstract::Influenza A viruses cause an annual contagious respiratory disease in humans and are responsible for periodic high-mortality human pandemics. Pandemic influenza A viruses usually result from the reassortment of gene segments between human and avian influenza viruses. These avian influenza virus gene segments need to a...


    pub_type: 杂志文章


    authors: Smith BL,Chen G,Wilke CO,Krug RM

    更新日期:2018-07-03 00:00:00

  • Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable Haemophilus influenzae.

    abstract::Biofilms play a critical role in the colonization, persistence, and pathogenesis of many human pathogens. Multiple mucosa-associated pathogens have evolved a mechanism of rapid adaptation, termed the phasevarion, which facilitates a coordinated regulation of numerous genes throughout the bacterial genome. This epigene...


    pub_type: 杂志文章


    authors: Brockman KL,Azzari PN,Branstool MT,Atack JM,Schulz BL,Jen FE,Jennings MP,Bakaletz LO

    更新日期:2018-09-18 00:00:00

  • Proposal of a Taxonomic Nomenclature for the Bacillus cereus Group Which Reconciles Genomic Definitions of Bacterial Species with Clinical and Industrial Phenotypes.

    abstract::The Bacillus cereus group comprises numerous closely related species, including bioterrorism agent B. anthracis, foodborne pathogen B. cereus, and biopesticide B. thuringiensis Differentiating organisms capable of causing illness or death from those used in industry is essential for risk assessment and outbreak prepar...


    pub_type: 杂志文章


    authors: Carroll LM,Wiedmann M,Kovac J

    更新日期:2020-02-25 00:00:00

  • Streptococcus pyogenes Is Associated with Idiopathic Cutaneous Ulcers in Children on a Yaws-Endemic Island.

    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...


    pub_type: 杂志文章


    authors: Griesenauer B,González-Beiras C,Fortney KR,Lin H,Gao X,Godornes C,Nelson DE,Katz BP,Lukehart SA,Mitjà O,Dong Q,Spinola SM

    更新日期:2021-01-12 00:00:00

  • A Functional Polymorphism-Mediated Disruption of EGR1/ADAM10 Pathway Confers the Risk of Sepsis Progression.

    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,...


    pub_type: 杂志文章,多中心研究


    authors: Chen F,Wang Y,Zhang W,Cai Y,Zhao T,Mai H,Tao S,Wei W,Li J,Chen X,Li X,Tang P,Fan W,Yang J,Ou M,Lu F,Lai Z,Chen H,Zou T,Sun F,Shao Y,Cui L

    更新日期:2019-08-06 00:00:00

  • Membrane Distribution of the Pseudomonas Quinolone Signal Modulates Outer Membrane Vesicle Production in Pseudomonas aeruginosa.

    abstract::The Pseudomonas quinolone signal (PQS) is an important quorum-sensing molecule in Pseudomonas aeruginosa that also mediates its own packaging and transport by stimulating outer membrane vesicle (OMV) formation. Because OMVs have been implicated in many virulence-associated behaviors, it is critical that we understand ...


    pub_type: 杂志文章


    authors: Florez C,Raab JE,Cooke AC,Schertzer JW

    更新日期:2017-08-08 00:00:00

  • RNA-Dependent Cysteine Biosynthesis in Bacteria and Archaea.

    abstract::The diversity of the genetic code systems used by microbes on earth is yet to be elucidated. It is known that certain methanogenic archaea employ an alternative system for cysteine (Cys) biosynthesis and encoding; tRNACys is first acylated with phosphoserine (Sep) by O-phosphoseryl-tRNA synthetase (SepRS) and then con...


    pub_type: 杂志文章


    authors: Mukai T,Crnković A,Umehara T,Ivanova NN,Kyrpides NC,Söll D

    更新日期:2017-05-09 00:00:00

  • Helicobacter pylori peptidoglycan modifications confer lysozyme resistance and contribute to survival in the host.

    abstract:UNLABELLED:The prominent host muramidase lysozyme cleaves bacterial peptidoglycan (PG), and the enzyme is abundant in mucosal secretions. The lytic enzyme susceptibility of Gram-negative bacteria and mechanisms they use to thwart lytic enzyme activity are poorly studied. We previously characterized a Helicobacter pylor...


    pub_type: 杂志文章


    authors: Wang G,Lo LF,Forsberg LS,Maier RJ

    更新日期:2012-12-04 00:00:00

  • Proteins needed to activate a transcriptional response to the reactive oxygen species singlet oxygen.

    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...


    pub_type: 杂志文章


    authors: Nam TW,Ziegelhoffer EC,Lemke RA,Donohue TJ

    更新日期:2013-01-08 00:00:00

  • Targeting Mannitol Metabolism as an Alternative Antimicrobial Strategy Based on the Structure-Function Study of Mannitol-1-Phosphate Dehydrogenase in Staphylococcus aureus.

    abstract::Mannitol-1-phosphate dehydrogenase (M1PDH) is a key enzyme in Staphylococcus aureus mannitol metabolism, but its roles in pathophysiological settings have not been established. We performed comprehensive structure-function analysis of M1PDH from S. aureus USA300, a strain of community-associated methicillin-resistant ...


    pub_type: 杂志文章


    authors: Nguyen T,Kim T,Ta HM,Yeo WS,Choi J,Mizar P,Lee SS,Bae T,Chaurasia AK,Kim KK

    更新日期:2019-07-09 00:00:00

  • Lipid Flippase Subunit Cdc50 Mediates Drug Resistance and Virulence in Cryptococcus neoformans.

    abstract:UNLABELLED:Cryptococcus neoformans is a human fungal pathogen and a major cause of fungal meningitis in immunocompromised individuals. Treatment options for cryptococcosis are limited. Of the two major antifungal drug classes, azoles are active against C. neoformans but exert a fungistatic effect, necessitating long tr...


    pub_type: 杂志文章


    authors: Huang W,Liao G,Baker GM,Wang Y,Lau R,Paderu P,Perlin DS,Xue C

    更新日期:2016-05-10 00:00:00

  • In Vitro Reconstitution of Functional Type III Protein Export and Insights into Flagellar Assembly.

    abstract::The type III secretion system (T3SS) forms the functional core of injectisomes, protein transporters that allow bacteria to deliver virulence factors into their hosts for infection, and flagella, which are critical for many pathogens to reach the site of infection. In spite of intensive genetic and biochemical studies...


    pub_type: 杂志文章


    authors: Terashima H,Kawamoto A,Tatsumi C,Namba K,Minamino T,Imada K

    更新日期:2018-06-26 00:00:00

  • 25-Hydroxycholesterol Inhibition of Lassa Virus Infection through Aberrant GP1 Glycosylation.

    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...


    pub_type: 杂志文章


    authors: Shrivastava-Ranjan P,Bergeron É,Chakrabarti AK,Albariño CG,Flint M,Nichol ST,Spiropoulou CF

    更新日期:2016-12-20 00:00:00

  • Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR).

    abstract::Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhib...


    pub_type: 杂志文章


    authors: Goodman DE,Pretto CD,Krepostman TA,Carnahan KE,Spindler KR

    更新日期:2019-04-23 00:00:00

  • Archaeal Haloarcula californiae Icosahedral Virus 1 Highlights Conserved Elements in Icosahedral Membrane-Containing DNA Viruses from Extreme Environments.

    abstract:UNLABELLED:Despite their high genomic diversity, all known viruses are structurally constrained to a limited number of virion morphotypes. One morphotype of viruses infecting bacteria, archaea, and eukaryotes is the tailless icosahedral morphotype with an internal membrane. Although it is considered an abundant morphot...


    pub_type: 杂志文章


    authors: Demina TA,Pietilä MK,Svirskaitė J,Ravantti JJ,Atanasova NS,Bamford DH,Oksanen HM

    更新日期:2016-07-19 00:00:00

  • RhlR-Regulated Acyl-Homoserine Lactone Quorum Sensing in a Cystic Fibrosis Isolate of Pseudomonas aeruginosa.

    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...


    pub_type: 杂志文章


    authors: Cruz RL,Asfahl KL,Van den Bossche S,Coenye T,Crabbé A,Dandekar AA

    更新日期:2020-04-07 00:00:00

  • Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa.

    abstract::Estrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid Pseudomonas aeruginosa in the airways of patients with chronic respiratory diseases, including cystic fibrosis. This results in long-term persistence, poorer clinical outcomes, and limited therapeutic options. In this study...


    pub_type: 杂志文章


    authors: Vidaillac C,Yong VFL,Aschtgen MS,Qu J,Yang S,Xu G,Seng ZJ,Brown AC,Ali MK,Jaggi TK,Sankaran J,Foo YH,Righetti F,Nedumaran AM,Mac Aogáin M,Roizman D,Richard JA,Rogers TR,Toyofuku M,Luo D,Loh E,Wohland T,Czarny

    更新日期:2020-09-29 00:00:00

  • The pause on Avian H5N1 influenza virus transmission research should be ended.

    abstract::A voluntary 60-day pause on avian H5N1 influenza virus transmission research was announced in January 2012 by the international community of influenza scientists engaged in this work to provide time to explain the benefits of such work and the risk mitigation measures in place. Subsequently, the pause was extended to ...


    pub_type: 杂志文章


    authors: Fouchier RA,García-Sastre A,Kawaoka Y

    更新日期:2012-11-01 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

  • EspC, an Autotransporter Protein Secreted by Enteropathogenic Escherichia coli, Causes Apoptosis and Necrosis through Caspase and Calpain Activation, Including Direct Procaspase-3 Cleavage.

    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...


    pub_type: 杂志文章


    authors: Serapio-Palacios A,Navarro-Garcia F

    更新日期:2016-06-21 00:00:00

  • Mechanism and Function of Antiviral RNA Interference in Mice.

    abstract::Distinct mammalian RNA viruses trigger Dicer-mediated production of virus-derived small-interfering RNAs (vsiRNA) and encode unrelated proteins to suppress vsiRNA biogenesis. However, the mechanism and function of the mammalian RNA interference (RNAi) response are poorly understood. Here, we characterized antiviral RN...


    pub_type: 杂志文章


    authors: Han Q,Chen G,Wang J,Jee D,Li WX,Lai EC,Ding SW

    更新日期:2020-08-04 00:00:00

  • Live and Diet by Your Gut Microbiota.

    abstract::Diet influences health in multiple ways. One important effect of diet is on the gut microbiota. The effects of diet are often related to an individual's specific microbiota composition. The close links between health, diet, and gut microbiota are illustrated in a new mouse model of sepsis where the combination of a hi...


    pub_type: 评论,杂志文章


    authors: Bassis CM

    更新日期:2019-10-08 00:00:00

  • Structural and Regulatory Changes in PBP4 Trigger Decreased β-Lactam Susceptibility in Enterococcus faecalis.

    abstract::Enterococcus faecalis strains resistant to penicillin and ampicillin are rare and have been associated with increases in quantities of low-affinity penicillin-binding protein 4 (PBP4) or with amino acid substitutions in PBP4. We report an E. faecalis strain (LS4828) isolated from a prosthetic knee joint that was subje...


    pub_type: 杂志文章


    authors: Rice LB,Desbonnet C,Tait-Kamradt A,Garcia-Solache M,Lonks J,Moon TM,D'Andréa ÉD,Page R,Peti W

    更新日期:2018-04-03 00:00:00

  • Contrasting life strategies of viruses that infect photo- and heterotrophic bacteria, as revealed by viral tagging.

    abstract::Ocean viruses are ubiquitous and abundant and play important roles in global biogeochemical cycles by means of their mortality, horizontal gene transfer, and manipulation of host metabolism. However, the obstacles involved in linking viruses to their hosts in a high-throughput manner bottlenecks our ability to underst...


    pub_type: 杂志文章


    authors: Deng L,Gregory A,Yilmaz S,Poulos BT,Hugenholtz P,Sullivan MB

    更新日期:2012-10-30 00:00:00

  • Streptococcus pneumoniae Transmission Is Blocked by Type-Specific Immunity in an Infant Mouse Model.

    abstract::Epidemiological studies on Streptococcus pneumoniae show that rates of carriage are highest in early childhood and that the major benefit of the pneumococcal conjugate vaccine (PCV) is a reduction in the incidence of nasopharyngeal colonization through decreased transmission within a population. In this study, we soug...


    pub_type: 杂志文章


    authors: Zangari T,Wang Y,Weiser JN

    更新日期:2017-03-14 00:00:00

  • The forgotten forefather: Joseph James Kinyoun and the founding of the National Institutes of Health.

    abstract::In celebrating the 125th anniversary of the National Institutes of Health (NIH) in August 2012, NIH has been examining its origins, its history, and the visionary men and women whose research have contributed to the saving and/or improving the quality of life of millions of people throughout the world. This minireview...


    pub_type: 传,历史文章,杂志文章,评审


    authors: Morens DM,Fauci AS

    更新日期:2012-06-26 00:00:00

  • Novel Insights into Conformational Rearrangements of the Bacterial Flagellar Switch Complex.

    abstract::The flagellar motor can spin in both counterclockwise (CCW) and clockwise (CW) directions. The flagellar motor consists of a rotor and multiple stator units, which act as a proton channel. The rotor is composed of the transmembrane MS ring made of FliF and the cytoplasmic C ring consisting of FliG, FliM, and FliN. The...


    pub_type: 杂志文章


    authors: Sakai T,Miyata T,Terahara N,Mori K,Inoue Y,Morimoto YV,Kato T,Namba K,Minamino T

    更新日期:2019-04-02 00:00:00

  • Elegant Science.

    abstract::Elegance is a prized quality in science that is associated with simplicity and explanatory power. This essay considers the qualities that make a scientific model, experiment, method, or theory "elegant," with a focus on the life sciences. We propose a definition of elegance that includes clarity, cleverness, correctne...


    pub_type: 社论


    authors: Casadevall A,Fang FC

    更新日期:2018-02-20 00:00:00

  • The Bactericidal Fatty Acid Mimetic 2CCA-1 Selectively Targets Pneumococcal Extracellular Polyunsaturated Fatty Acid Metabolism.

    abstract::Streptococcus pneumoniae, a major cause of pneumonia, sepsis, and meningitis worldwide, has the nasopharynges of small children as its main ecological niche. Depletion of pneumococci from this niche would reduce the disease burden and could be achieved using small molecules with narrow-spectrum antibacterial activity....


    pub_type: 杂志文章


    authors: Reithuber E,Nannapaneni P,Rzhepishevska O,Lindgren AEG,Ilchenko O,Normark S,Almqvist F,Henriques-Normark B,Mellroth P

    更新日期:2020-12-15 00:00:00

  • Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX3CR1+ Macrophages in Tissue Repair.

    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...


    pub_type: 杂志文章


    authors: Zaid A,Tharmarajah K,Mostafavi H,Freitas JR,Sheng KC,Foo SS,Chen W,Vider J,Liu X,West NP,Herrero LJ,Taylor A,Mackay LK,Getts DR,King NJC,Mahalingam S

    更新日期:2020-03-03 00:00:00