Malaria parasites survive in human erythrocytes by importing and digesting hemoglobin within a specialized organelle, the digestive vacuole (DV). Although chloroquine and other antimalarials act within the DV, the routes used by drugs, ions, and amino acids to cross the DV membrane remain poorly understood. Here, Saggu et al. used single DV patch-clamp to identify a novel large conductance anion channel as the primary conductive pathway on this organelle in Plasmodium falciparum, the most virulent human pathogen. This Big Vacuolar Anion Channel (BVAC) is primarily open at the DV resting membrane potential and undergoes complex voltage-dependent gating. Conductance and gating are unaffected by antimalarials targeting essential DV activities and are conserved on parasites with divergent drug susceptibility profiles, implicating an unexploited antimalarial target. Direct transport measurements at the DV membrane provide foundational insights into vacuolar physiology, should help clarify antimalarial action and drug resistance, and will guide therapy development against the parasite’s metabolic powerhouse. The image shows transmission electron micrographs of infected erythrocytes, colorized to the highlight the digestive vacuole.
Image Credit: Ryan Kissinger
Consensus View
A standardized nomenclature for the rods and cones of the vertebrate retina
PLOS Biology: published May 7, 2025 | https://doi.org/10.1371/journal.pbio.3003157
Perspectives
Accredited ocean sanctuaries for transforming captive cetacean care
PLOS Biology: published May 20, 2025 | https://doi.org/10.1371/journal.pbio.3003166
Is pathogen prediction possible?
PLOS Biology: published May 15, 2025 | https://doi.org/10.1371/journal.pbio.3003162
Old cytokine, new tricks: A refined model of interferon’s antiviral activity
PLOS Biology: published May 7, 2025 | https://doi.org/10.1371/journal.pbio.3003154
Primers
More science friction for less science fiction
PLOS Biology: published May 9, 2025 | https://doi.org/10.1371/journal.pbio.3003167
Related Articles
Population genetics of plant fungal threats: Insights from wheat powdery mildew
PLOS Biology: published May 5, 2025 | https://doi.org/10.1371/journal.pbio.3003151
Related Articles
Gene promoters are genomically encoded to facilitate histone exchange/incorporation
PLOS Biology: published May 13, 2025 | https://doi.org/10.1371/journal.pbio.3003160
Related Articles
Research Articles
Population genomics and molecular epidemiology of wheat powdery mildew in Europe
PLOS Biology: published May 2, 2025 | https://doi.org/10.1371/journal.pbio.3003097
Related Articles
Improved effectiveness of vaccination campaigns against rabies by reducing spatial heterogeneity in coverage
PLOS Biology: published May 5, 2025 | https://doi.org/10.1371/journal.pbio.3002872
Horizontal gene transfer of molecular weapons can reshape bacterial competition
PLOS Biology: published May 21, 2025 | https://doi.org/10.1371/journal.pbio.3003095
Object knowledge representation in the human visual cortex requires a connection with the language system
PLOS Biology: published May 20, 2025 | https://doi.org/10.1371/journal.pbio.3003161
Predictable motion is progressively extrapolated across temporally distinct processing stages in the human visual cortex
PLOS Biology: published May 23, 2025 | https://doi.org/10.1371/journal.pbio.3003189
Excitatory projections from the nucleus reuniens to the medial prefrontal cortex modulate pain and depression-like behaviors in mice
PLOS Biology: published May 20, 2025 | https://doi.org/10.1371/journal.pbio.3003170
Molecular states underlying neuronal cell type development and plasticity in the postnatal whisker cortex
PLOS Biology: published May 14, 2025 | https://doi.org/10.1371/journal.pbio.3003176
Loss of neuropeptidergic regulation of cholinergic transmission induces homeostatic compensation in muscle cells to preserve synaptic strength
PLOS Biology: published May 8, 2025 | https://doi.org/10.1371/journal.pbio.3003171
Cadherin-16 regulates acoustic sensory gating in zebrafish through endocrine signaling
PLOS Biology: published May 2, 2025 | https://doi.org/10.1371/journal.pbio.3003164
Upstream open reading frames dynamically modulate CLOCK protein translation to regulate circadian rhythms and sleep
PLOS Biology: published May 12, 2025 | https://doi.org/10.1371/journal.pbio.3003173
Phosphatase-independent activity of smooth-muscle calcineurin orchestrates a gene expression program leading to hypertension
PLOS Biology: published May 14, 2025 | https://doi.org/10.1371/journal.pbio.3003163
The m5C reader Ybx1 regulates embryonic cortical neurogenesis by promoting progenitor cell cycle progression
PLOS Biology: published May 28, 2025 | https://doi.org/10.1371/journal.pbio.3003175
Analysis of gene expression within individual cells reveals spatiotemporal patterns underlying Vibrio cholerae biofilm development
PLOS Biology: published May 16, 2025 | https://doi.org/10.1371/journal.pbio.3003187
The glycosomal ATP-dependent phosphofructokinase of Trypanosoma brucei operates also in the gluconeogenic direction
PLOS Biology: published May 16, 2025 | https://doi.org/10.1371/journal.pbio.3002938
Inhibition of the nucleolar RNA exosome facilitates adaptation to starvation
PLOS Biology: published May 21, 2025 | https://doi.org/10.1371/journal.pbio.3003190
H2A.Z deposition by the SWR complex is stimulated by polyadenine DNA sequences in nucleosomes
PLOS Biology: published May 12, 2025 | https://doi.org/10.1371/journal.pbio.3003059
Related Articles
Landscape of essential growth and fluconazole-resistance genes in the human fungal pathogen Cryptococcus neoformans
PLOS Biology: published May 22, 2025 | https://doi.org/10.1371/journal.pbio.3003184
Identification of a large anion channel required for digestive vacuole acidification and amino acid export in Plasmodium falciparum
PLOS Biology: published May 30, 2025 | https://doi.org/10.1371/journal.pbio.3003202
An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE
PLOS Biology: published May 27, 2025 | https://doi.org/10.1371/journal.pbio.3003208
Short Reports
Circadian rhythms are more resilient to pacemaker neuron disruption in female Drosophila
PLOS Biology: published May 6, 2025 | https://doi.org/10.1371/journal.pbio.3003146
Rhythm profiling using COFE reveals multi-omic circadian rhythms in human cancers in vivo
PLOS Biology: published May 27, 2025 | https://doi.org/10.1371/journal.pbio.3003196
Disruption of HaVipR1 confers Vip3Aa resistance in the moth crop pest Helicoverpa armigera
PLOS Biology: published May 29, 2025 | https://doi.org/10.1371/journal.pbio.3003165
The bacterial type three secretion system induces mechanoporation of vacuolar membranes
PLOS Biology: published May 1, 2025 | https://doi.org/10.1371/journal.pbio.3003135
Methods and Resources
Rewarding animals based on their subjective percepts is enabled by online Bayesian estimation of perceptual biases
PLOS Biology: published May 20, 2025 | https://doi.org/10.1371/journal.pbio.3002764
qByte: An open-source isothermal fluorimeter for democratizing analysis of nucleic acids, proteins and cells
PLOS Biology: published May 28, 2025 | https://doi.org/10.1371/journal.pbio.3003199
Meta-Research Article
Explosion of formulaic research articles, including inappropriate study designs and false discoveries, based on the NHANES US national health database
PLOS Biology: published May 8, 2025 | https://doi.org/10.1371/journal.pbio.3003152
Related Articles
Discovery Reports
Variation in adult sex ratios in tetrapods is linked to sex chromosomes through mortality differences between males and females
PLOS Biology: published May 12, 2025 | https://doi.org/10.1371/journal.pbio.3003156
An animal toxin-antidote system kills cells by creating a novel cation channel
PLOS Biology: published May 27, 2025 | https://doi.org/10.1371/journal.pbio.3003182
DnaJ mediates phage sensing by the bacterial NLR-related protein bNACHT25
PLOS Biology: published May 30, 2025 | https://doi.org/10.1371/journal.pbio.3003203
Update Article
Permeability selection of biologically relevant membranes matches the stereochemistry of life on Earth
PLOS Biology: published May 20, 2025 | https://doi.org/10.1371/journal.pbio.3003155