Molecular Biology and Physiology
Research Article | Molecular Biology and PhysiologyA Trypanosoma brucei ORFeome-Based Gain-of-Function Library Identifies Genes That Promote Survival during Melarsoprol TreatmentTrypanosomatid 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...
Research Article | Molecular Biology and PhysiologySppI Forms a Membrane Protein Complex with SppA and Inhibits Its Protease Activity in Bacillus subtilisOur 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...
Research Article | Molecular Biology and PhysiologyProvirus Mutations of Human T-Lymphotropic Virus 1 and 2 (HTLV-1 and HTLV-2) in HIV-1-Coinfected IndividualsHTLV-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...
Research Article | Molecular Biology and PhysiologyCandida albicans Double Mutants Lacking both EFG1 and WOR1 Can Still Switch to OpaqueThe 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...
Observation | Molecular Biology and PhysiologyDispensable Role of Mitochondrial Fission Protein 1 (Fis1) in the Erythrocytic Development of Plasmodium falciparumMalaria 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...
Research Article | Molecular Biology and PhysiologyRedefining the Clostridioides difficile σB Regulon: σB Activates Genes Involved in Detoxifying Radicals That Can Result from the Exposure to Antimicrobials and Hydrogen PeroxideSigma 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...
Research Article | Molecular Biology and PhysiologyPutative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of Aspergillus fumigatus to Different Stressors and Carbon SourcesAspergillus 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...
Research Article | Molecular Biology and PhysiologyWerner Syndrome Protein (WRN) Regulates Cell Proliferation and the Human Papillomavirus 16 Life Cycle during Epithelial DifferentiationHPV16 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...
Research Article | Molecular Biology and PhysiologyToxoplasma gondii AP2XII-2 Contributes to Proper Progression through S-Phase of the Cell CycleToxoplasma 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, ...
Research Article | Molecular Biology and PhysiologyAlternating Dynamics of oriC, SMC, and MksBEF in Segregation of Pseudomonas aeruginosa ChromosomeMechanisms 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...