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Molecular Biology and Physiology

  • Open Access
    A <span class="named-content genus-species" id="named-content-1">Trypanosoma brucei</span> ORFeome-Based Gain-of-Function Library Identifies Genes That Promote Survival during Melarsoprol Treatment
    Research Article | Molecular Biology and Physiology
    A Trypanosoma brucei ORFeome-Based Gain-of-Function Library Identifies Genes That Promote Survival during Melarsoprol Treatment

    Trypanosomatid parasites threaten the health of more than 1 billion people worldwide. Because their genomes are highly diverged from those of well-established eukaryotes, conservation is not always useful in assigning gene functions. However, it is precisely among the trypanosomatid-specific genes that ideal therapeutic targets might be found. Forward genetics approaches are an effective way to identify novel gene functions. We used an...

    McKenzie Carter, Stephanie Gomez, Sam Gritz, Stephen Larson, Eugenia Silva-Herzog, Hee-Sook Kim, Danae Schulz, Galadriel Hovel-Miner
  • Open Access
    SppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in <span class="named-content genus-species" id="named-content-1">Bacillus subtilis</span>
    Research Article | Molecular Biology and Physiology
    SppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in Bacillus subtilis

    Our study presents new insights into the molecular mechanism that regulates the activity of SppA, a widely conserved bacterial membrane protease. We show that the membrane proteins SppA and SppI form a complex in the Gram-positive model bacterium B. subtilis and that SppI inhibits SppA protease activity in vitro and in vivo. Furthermore, we...

    Gabriela Henriques, Stephen McGovern, Jolanda Neef, Minia Antelo-Varela, Friedrich Götz, Andreas Otto, Dörte Becher, Jan Maarten van Dijl, Matthieu Jules, Olivier Delumeau
  • Open Access
    Provirus Mutations of Human T-Lymphotropic Virus 1 and 2 (HTLV-1 and HTLV-2) in HIV-1-Coinfected Individuals
    Research Article | Molecular Biology and Physiology
    Provirus Mutations of Human T-Lymphotropic Virus 1 and 2 (HTLV-1 and HTLV-2) in HIV-1-Coinfected Individuals

    HTLV-1 and HTLV-2 are endemic to Brazil, and they have different effects in HIV/AIDS disease progression. HIV/HTLV-1 has been described as accelerating the progression to AIDS and death, while HIV/HTLV-2 slows the progression to AIDS. Provirus mutations of HTLV-1 were implicated in severe leukemia development and in problems in the diagnosis of HTLV-1; in contrast, provirus mutations of HTLV-2 had not been confirmed and associated with...

    Karoline Rodrigues Campos, Adele Caterino-de-Araujo
  • Open Access
    <span class="named-content genus-species" id="named-content-1">Candida albicans</span> Double Mutants Lacking both <em>EFG1</em> and <em>WOR1</em> Can Still Switch to Opaque
    Research Article | Molecular Biology and Physiology
    Candida albicans Double Mutants Lacking both EFG1 and WOR1 Can Still Switch to Opaque

    The switch from white to opaque in Candida albicans was discovered 33 years ago, but it is still unclear how it is regulated. A regulatory paradigm has emerged in which two transacting factors, Efg1 and Wor1, play central roles, Efg1 as a repressor of WOR1, which encodes an activator of the transition to the opaque phenotype. However, we show here that if...

    Yang-Nim Park, Claude Pujol, Deborah J. Wessels, David R. Soll
  • Open Access
    Dispensable Role of Mitochondrial Fission Protein 1 (Fis1) in the Erythrocytic Development of <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span>
    Observation | Molecular Biology and Physiology
    Dispensable Role of Mitochondrial Fission Protein 1 (Fis1) in the Erythrocytic Development of Plasmodium falciparum

    Malaria is responsible for over 230 million clinical cases and ∼half a million deaths each year. The single mitochondrion of the malaria parasite functions as a metabolic hub throughout the parasite’s developmental cycle (DC) and also as a source of ATP in certain stages. To pass on its essential functions, the parasite’s mitochondrion needs to be properly divided and segregated into all progeny during cell division via a process termed...

    Mulaka Maruthi, Liqin Ling, Jing Zhou, Hangjun Ke
  • Open Access
    Redefining the <span class="named-content genus-species" id="named-content-1">Clostridioides difficile</span> σ<sup>B</sup> Regulon: σ<sup>B</sup> Activates Genes Involved in Detoxifying Radicals That Can Result from the Exposure to Antimicrobials and Hydrogen Peroxide
    Research Article | Molecular Biology and Physiology
    Redefining the Clostridioides difficile σB Regulon: σB Activates Genes Involved in Detoxifying Radicals That Can Result from the Exposure to Antimicrobials and Hydrogen Peroxide

    Sigma B is the alternative sigma factor governing stress response in many Gram-positive bacteria. In C. difficile, a sigB mutant shows pleiotropic transcriptional effects. Here, we determine genes that are likely direct targets of σB by evaluating the transcriptional effects of σB overproduction, provide biochemical evidence of direct...

    Ilse M. Boekhoud, Annika-Marisa Michel, Jeroen Corver, Dieter Jahn, Wiep Klaas Smits
  • Open Access
    Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of <span class="named-content genus-species" id="named-content-1">Aspergillus fumigatus</span> to Different Stressors and Carbon Sources
    Research Article | Molecular Biology and Physiology
    Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of Aspergillus fumigatus to Different Stressors and Carbon Sources

    Aspergillus fumigatus is an important human-pathogenic fungal species that is responsible for a high incidence of infections in immunocompromised individuals. A. fumigatus high-osmolarity glycerol (HOG) and cell wall integrity pathways are important for the adaptation to different forms of...

    Lilian Pereira Silva, Dean Frawley, Leandro José de Assis, Ciara Tierney, Alastair B. Fleming, Ozgur Bayram, Gustavo Henrique Goldman
  • Open Access
    Werner Syndrome Protein (WRN) Regulates Cell Proliferation and the Human Papillomavirus 16 Life Cycle during Epithelial Differentiation
    Research Article | Molecular Biology and Physiology
    Werner Syndrome Protein (WRN) Regulates Cell Proliferation and the Human Papillomavirus 16 Life Cycle during Epithelial Differentiation

    HPV16 is the major human viral carcinogen, responsible for around 3 to 4% of all cancers worldwide. Our understanding of how the viral replication machinery interacts with host factors to control/activate the DNA damage response to promote the viral life cycle remains incomplete. Recently, we demonstrated a SIRT1-WRN axis that controls HPV16 replication, and here we demonstrate that this axis persists in clinical cervical lesions...

    Claire D. James, Dipon Das, Ethan L. Morgan, Raymonde Otoa, Andrew Macdonald, Iain M. Morgan
  • Open Access
    <span class="named-content genus-species" id="named-content-1">Toxoplasma gondii</span> AP2XII-2 Contributes to Proper Progression through S-Phase of the Cell Cycle
    Research Article | Molecular Biology and Physiology
    Toxoplasma gondii AP2XII-2 Contributes to Proper Progression through S-Phase of the Cell Cycle

    Toxoplasma gondii is a single-celled parasite that persists in its host by converting into a latent cyst stage. This work describes a new transcriptional factor called AP2XII-2 that plays a role in properly maintaining the growth rate of replicating parasites, which contributes to signals required for development into its dormant stage. Without AP2XII-2, ...

    Sandeep Srivastava, Michael W. White, William J. Sullivan
  • Open Access
    Alternating Dynamics of <em>oriC</em>, SMC, and MksBEF in Segregation of <span class="named-content genus-species" id="named-content-1">Pseudomonas aeruginosa</span> Chromosome
    Research Article | Molecular Biology and Physiology
    Alternating Dynamics of oriC, SMC, and MksBEF in Segregation of Pseudomonas aeruginosa Chromosome

    Mechanisms that define the chromosome as a structural entity remain unknown. Key elements in this process are condensins, which globally organize chromosomes and contribute to their segregation. This study characterized condensin and chromosome dynamics in Pseudomonas aeruginosa, which harbors condensins from two major protein superfamilies, SMC and MksBEF. The study...

    Hang Zhao, Bijit K. Bhowmik, Zoya M. Petrushenko, Valentin V. Rybenkov

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