Zombie malaria parasites.

Natural infections are distinct from those of laboratory-or zombie-strains.

Dual CRISPR/Cas13a Cascade Strand Displacement-Triggered Transcription for Point-of-Care Detection of Plasmodium in Asymptomatic Malaria.

Asymptomatic infections of Plasmodium parasites are major obstacles to malaria control and elimination. A sensitive, specific, and user-friendly method is urgently needed for point-of-care (POC) Plasmodium diagnostics in asymptomatic malaria, especially in resource-limited settings. In this work, we present a POC method (termed Cas13a-SDT) based on the cascade sequence recognition and signal amplification of dual Cas13a trans-cleavage and strand displacement-triggered transcription (SDT). Cas13a-SDT not only achieves exceptional specificity in discriminating the target RNA from nontarget RNAs with any cross-interaction but also meets the sensitivity criterion set by the World Health Organization (WHO) for effective malaria detection. Remarkably, this novel method was successfully applied to screen malaria in asymptomatic infections from clinical samples. The proposed method provides a user-friendly and visually interpretable output mode while maintaining high accuracy and reliability comparable to RT-PCR. These excellent features demonstrate the significant potential of Cas13a-SDT for POC diagnosis of Plasmodium infections, laying a vital foundation for advancing malaria control and elimination efforts.

Molecular tools are crucial for malaria elimination.

The eradication of Plasmodium parasites, responsible for malaria, is a daunting global public health task. It requires a comprehensive approach that addresses symptomatic, asymptomatic, and submicroscopic cases. Overcoming this challenge relies on harnessing the power of molecular diagnostic tools, as traditional methods like microscopy and rapid diagnostic tests fall short in detecting low parasitaemia, contributing to the persistence of malaria transmission. By precisely identifying patients of all types and effectively characterizing malaria parasites, molecular tools may emerge as indispensable allies in the pursuit of malaria elimination. Furthermore, molecular tools can also provide valuable insights into parasite diversity, drug resistance patterns, and transmission dynamics, aiding in the implementation of targeted interventions and surveillance strategies. In this review, we explore the significance of molecular tools in the pursuit of malaria elimination, shedding light on their key contributions and potential impact on public health.

Effect of spatiotemporal variables on abundance, biting activity and parity of Nyssorhynchus darlingi (Diptera: Culicidae) in peri-Iquitos, Peru.

BACKGROUND: In malaria endemic regions of the Peruvian Amazon, rainfall together with river level and breeding site availability drive fluctuating vector mosquito abundance and human malaria cases, leading to temporal heterogeneity. The main variables influencing spatial transmission include location of communities, mosquito behaviour, land use/land cover, and human ecology/behaviour. The main objective was to evaluate seasonal and microgeographic biting behaviour of the malaria vector Nyssorhynchus (or Anopheles) darlingi in Amazonian Peru and to investigate effects of seasonality on malaria transmission. METHODS: We captured mosquitoes from 18:00 to 06:00 h using Human Landing Catch in two riverine (Lupuna, Santa Emilia) and two highway (El Triunfo, Nuevo Horizonte) communities indoors and outdoors from 8 houses per community, during the dry and rainy seasons from February 2016 to January 2017. We then estimated parity rate, daily survival and age of a portion of each collection of Ny. darlingi. All collected specimens of Ny. darlingi were tested for the presence of Plasmodium vivax or Plasmodium falciparum sporozoites using real-time PCR targeting the small subunit of the 18S rRNA. RESULTS: Abundance of Ny. darlingi varied across village, season, and biting behaviour (indoor vs outdoor), and was highly significant between rainy and dry seasons (p < 0.0001). Biting patterns differed, although not significantly, and persisted regardless of season, with peaks in highway communities at ~ 20:00 h in contrast to biting throughout the night (i.e., 18:00-06:00) in riverine communities. Of 3721 Ny. darlingi tested for Plasmodium, 23 (0.62%) were infected. We detected Plasmodium-infected Ny. darlingi in both community types and most (20/23) were captured outdoors during the rainy season; 17/23 before midnight. Seventeen Ny. darlingi were infected with P. vivax, and 6 with P. falciparum. No infected Ny. darlingi were captured during the dry season. Significantly higher rates of parity were detected in Ny. darlingi during the rainy season (average 64.69%) versus the dry season (average 36.91%) and by community, Lupuna, a riverine village, had the highest proportion of parous to nulliparous females during the rainy season. CONCLUSIONS: These data add a seasonal dimension to malaria transmission in peri-Iquitos, providing more evidence that, at least locally, the greatest risk of malaria transmission is outdoors during the rainy season mainly before midnight, irrespective of whether the community was located adjacent to the highway or along the river.

Inhibition of malaria and babesiosis parasites by putative red blood cell targeting small molecules.

Background: Chemotherapies for malaria and babesiosis frequently succumb to the emergence of pathogen-related drug-resistance. Host-targeted therapies are thought to be less susceptible to resistance but are seldom considered for treatment of these diseases. Methods: Our overall objective was to systematically assess small molecules for host cell-targeting activity to restrict proliferation of intracellular parasites. We carried out a literature survey to identify small molecules annotated for host factors implicated in Plasmodium falciparum infection. Alongside P. falciparum, we implemented in vitro parasite susceptibility assays also in the zoonotic parasite Plasmodium knowlesi and the veterinary parasite Babesia divergens. We additionally carried out assays to test directly for action on RBCs apart from the parasites. To distinguish specific host-targeting antiparasitic activity from erythrotoxicity, we measured phosphatidylserine exposure and hemolysis stimulated by small molecules in uninfected RBCs. Results: We identified diverse RBC target-annotated inhibitors with Plasmodium-specific, Babesia-specific, and broad-spectrum antiparasitic activity. The anticancer MEK-targeting drug trametinib is shown here to act with submicromolar activity to block proliferation of Plasmodium spp. in RBCs. Some inhibitors exhibit antimalarial activity with transient exposure to RBCs prior to infection with parasites, providing evidence for host-targeting activity distinct from direct inhibition of the parasite. Conclusions: We report here characterization of small molecules for antiproliferative and host cell-targeting activity for malaria and babesiosis parasites. This resource is relevant for assessment of physiological RBC-parasite interactions and may inform drug development and repurposing efforts.

[Molecular mimicry between Plasmodium sp and Guillain-Barre syndrome antigens]. / Mimetismo molecular entre el Plasmodium sp y los antígenos del síndrome de Guillain-Barre.

OBJECTIVE: Analyze the molecular mimicry between Plasmodium spp. and autoantigens associated with GBS, identifying possible antigenic epitopes. METHODS: PSI-Blast, Praline, Emboss, Protein Data Bank, Swiss Model Server, AlphaFold 2, Ellipro and PyMol 2.3 were used to search for homologies, perform alignments, obtain protein structures, and predict epitopes. RESULTS: 17 autoantigens and seven immunological targets of the peripheral nervous system were included, identifying 72 possible epitopes associated with GBS. From the proteome of Plasmodium spp. (298 proteins), only two showed similarities close to 30% with TRIM21 and BACE1, generating seven possible epitopes. CONCLUSION: No significant homologies were observed between the proteome of GBS and Plasmodium spp. The exploration of other mechanisms such as immune-mediated capillary damage, Epitope Spreading or Bystander Activation is suggested to explain the mentioned association. These findings underscore the need to clarify the etiology of autoimmune diseases and the role of pathogens. The need for experimental studies to validate these results is emphasized.

OBJETIVO: Analizar el mimetismo molecular entre Plasmodium spp. y autoantígenos asociados al SGB, identificando posibles epítopos antigénicos. MÉTODOS: Se emplearon PSI-Blast, Praline, Emboss, Protein Data Bank, Swiss Model Server, AlphaFold 2, Ellipro y PyMol 2.3 para buscar homologías, realizar alineamientos, obtener estructuras proteicas y predecir epítopos. RESULTADOS: Se incluyeron 17 autoantígenos y siete objetivos inmunológicos del sistema nervioso periférico, identificándose 72 posibles epítopos asociados al SGB. Del proteoma de Plasmodium spp. (298 proteínas), solo dos mostraron similitud cercana al 30% con TRIM21 y BACE1, generando siete posibles epítopos. CONCLUSIÓN: No se observaron homologías significativas entre el proteoma de SGB y Plasmodium spp. Se sugiere la exploración de otros mecanismos como el daño capilar inmunomediado, Epitope Spreading o Bystander Activation para explicar la asociación mencionada. Estos hallazgos subrayan la necesidad de aclarar la etiología de las enfermedades autoinmunes y el papel de los patógenos. Se enfatiza la necesidad de estudios experimentales para validar estos resultados.

Higher body condition with infection by Haemoproteus parasites in Bananaquits (Coereba flaveola).

Parasite transmission is a heterogenous process in host-parasite interactions. This heterogeneity is particularly apparent in vector-borne parasite transmission where the vector adds an additional level of complexity. Haemosporidian parasites, a widespread protist, cause a malaria-like disease in birds globally, but we still have much to learn about the consequences of infection to hosts' health. In the Caribbean, where malarial parasites are endemic, studying host-parasites interactions may give us important insights about energetic trade-offs involved in malarial parasites infections in birds. In this study, we tested the consequences of Haemoproteus infection on the Bananaquit, a resident species of Puerto Rico. We also tested for potential sources of individual heterogeneity in the consequences of infection such as host age and sex. To quantify the consequences of infection to hosts' health we compared three complementary body condition indices between infected and uninfected individuals. Our results showed that Bananaquits infected by Haemoproteus had higher body condition than uninfected individuals. This result was consistent among the three body condition indices. Still, we found no clear evidence that this effect was mediated by host age or sex. We discuss a set of non-mutually exclusive hypotheses that may explain this pattern including metabolic syndrome, immunological responses leading to host tolerance or resistance to infection, and potential changes in consumption rates. Overall, our results suggest that other mechanisms, may drive the consequences of avian malarial infection.

Who was the first to visualize the malaria parasite?

Human malaria, an ancient tropical disease, is caused by infection with protozoan parasites belonging to the genus Plasmodium and is transmitted by female mosquitoes of the genus Anopheles. Our understanding of human malaria parasites began officially in 1880 with their discovery in the blood of malaria patients by Charles Louis Alphonse Lavéran (1845-1922), a French army officer working in Algeria. A claim for priority was made by Philipp Friedrich Hermann Klencke (1813-1881) in 1843, who wrote a chapter entitled: "Marvellous parallelism between the manifestations of vertigo and the presence of animalcule vacuoles in living blood." We should not lose sight of this old controversy, which is rarely mentioned in historical reviews on malaria.

Exploring mosquito abundance and Plasmodium infection through nested-PCR: implications for disease surveillance and control.

The Plasmodium is responsible for malaria which poses a major health threat, globally. This study is based on the estimation of the relative abundance of mosquitoes, and finding out the correlations of meteorological parameters (temperature, humidity and rainfall) with the abundance of mosquitoes. In addition, this study also focused on the use of nested PCR (species-specific nucleotide sequences of 18S rRNA genes) to explore the Plasmodium spp. in female Anopheles. In the current study, the percentage relative abundance of Culex mosquitoes was 57.65% and Anopheles 42.34% among the study areas. In addition, the highest number of mosquitoes was found in March in district Mandi Bahauddin at 21 °C (Tmax = 27, Tmin = 15) average temperature, 69% average relative humidity and 131 mm rainfall, and these climatic factors were found to affect the abundance of the mosquitoes, directly or indirectly. Molecular analysis showed that overall, 41.3% of the female Anopheles pools were positive for genus Plasmodium. Among species, the prevalence of Plasmodium (P.) vivax (78.1%) was significantly higher than P. falciparum (21.9%). This study will be helpful in the estimation of future risk of mosquito-borne diseases along with population dynamic of mosquitoes to enhance the effectiveness of vector surveillance and control programs.

The molecular mechanisms driving Plasmodium cell division.

Malaria, a vector borne disease, is a major global health and socioeconomic problem caused by the apicomplexan protozoan parasite Plasmodium. The parasite alternates between mosquito vector and vertebrate host, with meiosis in the mosquito and proliferative mitotic cell division in both hosts. In the canonical eukaryotic model, cell division is either by open or closed mitosis and karyokinesis is followed by cytokinesis; whereas in Plasmodium closed mitosis is not directly accompanied by concomitant cell division. Key molecular players and regulatory mechanisms of this process have been identified, but the pivotal role of certain protein complexes and the post-translational modifications that modulate their actions are still to be deciphered. Here, we discuss recent evidence for the function of known proteins in Plasmodium cell division and processes that are potential novel targets for therapeutic intervention. We also identify key questions to open new and exciting research to understand divergent Plasmodium cell division.

CD4 T Cell-Derived IL-21 Is Critical for Sustaining Plasmodium Infection-Induced Germinal Center Responses and Promoting the Selection of Memory B Cells with Recall Potential.

Development of Plasmodium-specific humoral immunity is critically dependent on CD4 Th cell responses and germinal center (GC) reactions during blood-stage Plasmodium infection. IL-21, a cytokine primarily produced by CD4 T cells, is an essential regulator of affinity maturation, isotype class-switching, B cell differentiation, and maintenance of GC reactions in response to many infection and immunization models. In models of experimental malaria, mice deficient in IL-21 or its receptor IL-21R fail to develop memory B cell populations and are not protected against secondary infection. However, whether sustained IL-21 signaling in ongoing GCs is required for maintaining GC magnitude, organization, and output is unclear. In this study, we report that CD4+ Th cells maintain IL-21 expression after resolution of primary Plasmodium yoelii infection. We generated an inducible knockout mouse model that enabled cell type-specific and timed deletion of IL-21 in peripheral, mature CD4 T cells. We found that persistence of IL-21 signaling in active GCs had no impact on the magnitude of GC reactions or their capacity to produce memory B cell populations. However, the memory B cells generated in the absence of IL-21 exhibited reduced recall function upon challenge. Our data support that IL-21 prevents premature cellular dissolution within the GC and promotes stringency of selective pressures during B cell fate determination required to produce high-quality Plasmodium-specific memory B cells. These data are additionally consistent with a temporal requirement for IL-21 in fine-tuning humoral immune memory responses during experimental malaria.

Dynamics of Plasmodium species and genotype diversity in adults with asymptomatic infection in Gabon.

OBJECTIVES: We investigated the diversity and dynamics of Plasmodium infection in serially collected samples from asymptomatic participants of a clinical trial assessing the efficacy and safety of ivermectin in Gabon. We checked whether the baseline sample reflected the P. falciparum genotype and Plasmodium species diversity seen over 7 days of follow-up. METHODS: Blood samples were collected at inclusion, every 8 hours until hour 72, daily until day 7, and on day 14. Plasmodium species was determined by qPCR and pfmsp1 length polymorphism was assessed for P. falciparum genotyping. RESULTS: In 17/48 (35%) individuals, all pfmsp1 genotypes identified during the assessed period were detected at baseline; in 31/48 (65%), new genotypes were found during follow-up. Additional sampling at hour 24 allowed the identification of all genotypes seen over 7 days in 50% of the individuals. Ivermectin did not impact the genotype dynamics. Mixed Plasmodium spp. infections were detected in 28/49 (57%) individuals at baseline, and detection of non-falciparum infections during follow-up varied. CONCLUSIONS: Our results reveal complex intra-host dynamics of P. falciparum genotypes and Plasmodium species and underscore the importance of serial sampling in clinical trials for antimalarial drugs with asymptomatically P. falciparum-infected individuals. This might allow a more accurate identification of genotypes in multiple infections, impacting the assessment of drug efficacy.

New insight into avian malaria vectors in New Zealand.

BACKGROUND: Mosquitoes (Culicidae) are vectors for most malaria parasites of the Plasmodium species and are required for Plasmodium spp. to complete their life cycle. Despite having 16 species of mosquitoes and the detection of many Plasmodium species in birds, little is known about the role of different mosquito species in the avian malaria life cycle in New Zealand. METHODS: In this study, we used nested polymerase chain reaction (PCR) and real-time PCR to determine Plasmodium spp. prevalence and diversity of mitochondrial cytochrome b gene sequences in wild-caught mosquitoes sampled across ten sites on the North Island of New Zealand during 2012-2014. The mosquitoes were pooled by species and location collected, and the thorax and abdomens were examined separately for Plasmodium spp. DNA. Akaike information criterion (AIC) modeling was used to test whether location, year of sampling, and mosquito species were significant predictors of minimum infection rates (MIR). RESULTS: We collected 788 unengorged mosquitoes of six species, both native and introduced. The most frequently caught mosquito species were the introduced Aedes notoscriptus and the native Culex pervigilans. Plasmodium sp DNA was detected in 37% of matched thorax and abdomen pools. When considered separately, 33% of abdomen and 23% of thorax pools tested positive by nested PCR. The MIR of the positive thorax pools from introduced mosquito species was 1.79% for Ae. notoscriptus and 0% for Cx. quinquefasciatus, while the MIR for the positive thorax pools of native mosquito species was 4.9% for Cx. pervigilans and 0% for Opifex fuscus. For the overall MIR, site and mosquito species were significant predictors of Plasmodium overall MIR. Aedes notoscriptus and Cx. pervigilans were positive for malaria DNA in the thorax samples, indicating that they may play a role as avian malaria vectors. Four different Plasmodium lineages (SYAT05, LINN1, GRW6, and a new lineage of P (Haemamoeba) sp. AENOT11) were identified in the pooled samples. CONCLUSIONS: This is the first detection of avian Plasmodium DNA extracted from thoraxes of native Culex and introduced Aedes mosquito species in New Zealand and therefore the first study providing an indication of potential vectors in this country.

Complex Endosymbiosis II: The Nonphotosynthetic Plastid of Apicomplexa Parasites (The Apicoplast) and Its Integrated Metabolism.

Chloroplasts are essential organelles that are responsible for photosynthesis in a wide range of organisms that have colonized all biotopes on Earth such as plants and unicellular algae. Interestingly, a secondary endosymbiotic event of a red algal ancestor gave rise to a group of organisms that have adopted an obligate parasitic lifestyle named Apicomplexa parasites. Apicomplexa parasites are some of the most widespread and poorly controlled pathogens in the world. These infectious agents are responsible for major human diseases such as toxoplasmosis, caused by Toxoplasma gondii, and malaria, caused by Plasmodium spp. Most of these parasites harbor this relict plastid named the apicoplast, which is essential for parasite survival. The apicoplast has lost photosynthetic capacities but is metabolically similar to plant and algal chloroplasts. The apicoplast is considered a novel and important drug target against Apicomplexa parasites. This chapter focuses on the apicoplast of apicomplexa parasites, its maintenance, and its metabolic pathways.

Malaria infection and predictor factors among Chadian nomads' children.

BACKGROUND: In Chad, malaria remains a significant public health concern, particularly among nomadic populations. Geographical factors and the mobility of human populations have shown to be associated with the diversity of Plasmodium species. The study aims to describe the malaria prevalence among nomadic children and to investigate its associated factors. METHODS: A cross-sectional study was conducted in February and October 2021 among nomadic communities in Chad. Blood sample were collected and tested from 187 Arab, Fulani and Dazagada nomadic children aged 3-59 months using malaria rapid diagnostic test (RDT). A structured electronic questionnaire was administered to their parents to collect information about the socio­economic data. Malaria testing results were categorized according to the SD BIOLINE Malaria Ag Pf/Pan RDT procedures. Logistic regression analysis was used to determine key risk factors explaining the prevalence of malaria. STATA version IC 13 was used for statistical analysis. RESULTS: The overall malaria prevalence in nomadic children was 24.60%, with 65.20% being Plasmodium falciparum species and 34.8% mixed species. Boys were twice as likely (COR = 1.83; 95% CI, 0.92-3.62; p = 0.083) to have malaria than girls. Children whose parents used to seek traditional drugs were five times more likely (AOR = 5.59; 95% CI, 1.40-22.30, p = 0.015) to have malaria than children whose parents used to seek health facilities. Children whose parents reported spending the last night under a mosquito net were one-fifth as likely (AOR = 0.17; 95% CI, 0.03-0.90, p = 0.037) to have malaria compared to children whose parents did not used a mosquito net. Furthermore, Daza children were seventeen times (1/0.06) less likely (AOR = 0.06; 95% CI, 0.01-0.70, p = 0.024) to have malaria than Fulani children and children from households piped water as the main source were seven times more likely (AOR = 7.05; 95% CI, 1.69-29.45; p = 0.007) to have malaria than those using surface water. CONCLUSIONS: Malaria remains a significant public health issue in the nomadic communities of Chad. Community education and sensitization programs within nomad communities are recommended to raise awareness about malaria transmission and control methods, particularly among those living in remote rural areas. The National Malaria Control Program (NMCP) should increase both the coverage and use of long-lasting insecticidal nets (LLINs) and seasonal malaria chemoprevention (SMC) in addition to promoting treatment-seeking behaviors in nomadic communities.

Biomolecular interactions between Plasmodium and human host: A basis of targeted antimalarial therapy.

Malaria is one of the serious health concerns worldwide as it remains a clinical challenge due to the complex life cycle of the malaria parasite and the morphological changes it undergoes during infection. The malaria parasite multiplies rapidly and spreads in the population by changing its alternative hosts. These various morphological stages of the parasite in the human host cause clinical symptoms (anemia, fever, and coma). These symptoms arise due to the preprogrammed biology of the parasite in response to the human pathophysiological response. Thus, complete elimination becomes one of the major health challenges. Although malaria vaccine(s) are available in the market, they still contain to cause high morbidity and mortality. Therefore, an approach for eradication is needed through the exploration of novel molecular targets by tracking the epidemiological changes the parasite adopts. This review focuses on the various novel molecular targets.

Cerebral malaria presenting as nonconvulsive status epilepticus: a case report.

BACKGROUND: Malaria is an infectious malady caused by Plasmodium parasites, cerebral malaria standing out as one of its most severe complications. Clinical manifestation include elevated body temperature, loss of consciousness, and seizures. However, reports of cerebral malaria presenting as nonconvulsive status epilepticus are extremely rare. The case presented involves psychiatric symptoms, with the electroencephalogram indicated nonconvulsive status epilepticus associated with cerebral malaria. CASE PRESENTATION: A 53-year-old male, was urgently admitted, due to confusion and abnormal behaviour for 10 h. The patient returned to China after developing a fever while working in Tanzania two months ago. The blood smear revealed Plasmodium vivax and Plasmodium falciparum, and he was diagnosed with malaria. He recovered following anti-malarial treatment. After admission, the patient was confused, unable to communicate normally, and unwilling to cooperate with the physical examination. Plasmodium was not found in the blood smear, but the DNA sequence of P. falciparum was discovered using metagenomic next-generation sequencing of cerebrospinal fluid. Brain MRI revealed no significant abnormalities. Continuous electroencephalogram monitoring revealed that the patient had non-convulsive status epilepticus, which was treated with diazepam and levetiracetam. The patient had normal consciousness and behaviour. He received anti-malarial treatment for two weeks and fully recovered. CONCLUSIONS: This case demonstrates that nonconvulsive status epilepticus can be a manifestation of cerebral malaria. It is imperative for attending physicians to heighten vigilance when encountering patients with a history of travel to malaria-endemic regions or a prior malaria infection, especially in the presence of unusual clinical presentations.

Design, synthesis and Anti-Plasmodial activity of Mortiamide-Lugdunin conjugates.

In this study, two linear and corresponding cyclic heptapeptide versions of mortiamide A-lugdunin hybrids were designed and synthesized by integrating an anti-malarial peptide epitope derived from Mortiamide A, combined with four residues known for their membrane interactions. Using this synthetic strategy, the sequence of mortiamide A was partly re-engineered with an epitope sequence of lugdunin along with an amino acid replacement using all-L and D/L configurations. Importantly, the re-engineered cyclic mortiamides with all-L (3) and D/L (4) configurations exhibited promising anti-malarial activities against the P. falciparum drug-sensitive TM4/8 strain with half-maximal inhibitory concentration (IC50) values of 6.2 ± 0.5 and 4.8 ± 0.1 µM, respectively. Additionally, they exhibited anti-malarial activities against the P. falciparum multidrug-resistant V1/S strain with IC50 values of 5.0 ± 2.6 and 3.7 ± 0.7 µM, respectively. Interestingly, a linear re-engineered mortiamide with D/L configuration (2) exhibited promising anti-malarial activities, surpassing those of the re-engineered cyclic mortiamides (3 and 4), against both the P. falciparum sensitive TM4/8 and multidrug-resistant V1/S strains with IC50 values of 3.6 ± 0.5 and 2.8 ± 0.7 µM (IC50 of Mortiamide A = 7.85 ± 0.97, 5.31 ± 0.24 µM against 3D7 and Dd2 strains) without any cytotoxicity at >100 µM. The presence of D/L forms in a linear structure significantly impacted the anti-malarial activity against both the P. falciparum sensitive TM4/8 strain and the multidrug-resistant V1/S strain.

Size-dependent self-avoidance enables superdiffusive migration in macroscopic unicellulars.

Many cells face search problems, such as finding food, mates, or shelter, where their success depends on their search strategy. In contrast to other unicellular organisms, the slime mold Physarum polycephalum forms a giant network-shaped plasmodium while foraging for food. What is the advantage of the giant cell on the verge of multicellularity? We experimentally study and quantify the migration behavior of P. polycephalum plasmodia on the time scale of days in the absence and presence of food. We develop a model which successfully describes its migration in terms of ten data-derived parameters. Using the mechanistic insights provided by our data-driven model, we find that regardless of the absence or presence of food, P. polycephalum achieves superdiffusive migration by performing a self-avoiding run-and-tumble movement. In the presence of food, the run duration statistics change, only controlling the short-term migration dynamics. However, varying organism size, we find that the long-term superdiffusion arises from self-avoidance determined by cell size, highlighting the potential evolutionary advantage that this macroscopically large cell may have.