mSphere® An ASM Access® Publication

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Mosquito cell lines are essential tools for arbovirus research. Endogenous viral elements (EVEs) are prevalent in mosquito genomes, yet their functional effects on host immune responses remain unclear, potentially complicating experimental interpretations. In this study, we systematically characterized endogenous mosquito densovirus-like elements (EMLs) within the Aedes aegypti Aag2 cell line and found that these endogenous EMLs are transcriptionally active but translationally defective. The...

Systemic fungal infections cause an estimated 3.8 million deaths annually, approximately 10% of which are caused by drug-resistant infections. With only five classes of antifungal drugs, treatment options are limited. Here, we explore synergistic drug combinations-when the efficacy of two drugs combined is greater than expected based on the sum of each individual drug's efficacy-to improve treatment of drug-resistant Cryptococcus neoformans and Candida albicans. Chlorpromazine acts...

Echinocandin antifungal drugs, such as caspofungin, inhibit β-1,3-glucan synthesis to impair cell wall formation. Caspofungin is effective in the clinic against Aspergillus and Candida species but ineffective against Cryptococcus neoformans, the fungus responsible for life-threatening meningoencephalitis in immunocompromised individuals. The mechanisms of caspofungin resistance in C. neoformans are associated with calcineurin signaling and functions that influence membrane and cell wall...

DNA-based vaccines have been developed and tested against a range of infectious agents, including influenza A viruses (IAV). Bacterial plasmid DNA is widely used as a vector for delivering genes encoding vaccine immunogens. However, the inclusion of antibiotic resistance genes in conventional plasmid constructs raises safety concerns. Linear DNA expression cassettes produced via PCR that lack antibiotic resistance genes, and bacterial sequences can serve as a safer alternative vector. In this...

Natural products have provided most of our modern pharmacopeia, serving as active molecules or scaffolds for active molecules. Their use in drug development is often inspired by their traditional or historical medical use. For many decades, this discovery pipeline has focused on identifying a single molecule responsible for much of the biological activity of a "raw" natural product preparation (e.g., a whole-plant extract) and scoping this molecule for clinical potential. However, it is...

Acid mine drainage (AMD) is a global pollution problem characterized by low pH and high concentrations of metals. Active remediation is often cost-prohibitive, but Fe(II)-oxidizing microbes may be used for passive bioremediation. To leverage these species, we must understand the factors that control their distribution. Here, we examined the environmental and ecological factors that control these species with the aim of determining if microbial seeding is a viable remediation strategy. Although...

An effective HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs) that bind relatively conserved regions of the otherwise highly variable envelope glycoprotein. Among these, VRC01-class bNAbs are a reproducible antibody class that bind the CD4-binding site through genetic features encoded by the VH1-2 heavy chain and a light chain containing a rare five-amino-acid-long complementarity-determining region 3 (CDRL3). We previously developed a germline-targeting...

Post-translational modifications, including ubiquitination, have emerged as important regulators of viral infection and the host innate immune response. We screened the proteins of SARS-CoV-2 for ubiquitination and identified the RNA-dependent RNA polymerase (RdRp) NSP12 as being ubiquitinated, which has not previously been reported. Importantly, we confirmed that NSP12 is ubiquitinated during SARS-CoV-2 infection, and the NSP12 proteins of different coronaviruses are differentially associated...

Vaccines that elicit balanced, protective immunity to all four dengue virus (DENV) types are needed to reduce the global burden of dengue disease. Achieving this goal has been a challenge for dengue vaccine developers, particularly when immunizing dengue immunologically naïve individuals. In this randomized, phase I, open-label study of 40 healthy adults, we evaluated a heterologous, tetravalent purified inactivated vaccine (PIV) prime and a tetravalent live attenuated vaccine (LAV) boost. We...

Temperature is known to affect organismal size, yet the underlying mechanism has been debated. Here, we develop a simple growth model of heterotrophic plankton and explain the temperature-size effect based on the demand and supply of oxygen. The model applies the growth rate-temperature relationship based on protein stability, capturing six data sets of a planktonic ciliate Urotricha. The model then computes the oxygen demand, based on the growth rate, which must be balanced by the diffusive...

Every year, billions of passengers, pets, and livestock are transported by air, which increases the risk of a global spread of pathogens like severe acute respiratory syndrome coronavirus 1 and 2, H1N1 influenza, the Ebola virus, and foot-and-mouth disease virus. However, due to its complexity and high safety standards, aircraft decontamination is limited to manual surface disinfection, and an approved method for disinfecting otherwise inaccessible areas is still unavailable. To address this...

Phytophthora nicotianae is a persistent and highly destructive soilborne oomycete that causes black shank of tobacco and continues to threaten its production despite integrated management. Although soil microbiomes are increasingly recognized as important components of disease outcomes, little is known about how soil microbial communities vary with P. nicotianae DNA concentrations and black shank pressure under field conditions. We examined relationships among 17 soil physicochemical properties,...

In 2016, researchers at the J. Craig Venter Institute produced JCVI-Syn3.0, a derivative of Mycoplasma mycoides subsp. capri Large Colony strain GM12 with a re-engineered, minimized genome. The minimal synthetic genome of 532 kbp encodes 473 genes, selected from ∼910 parent genes on the basis of their indispensability, that is, a lethal phenotype caused by a knockout of each such gene. Among these genes, 438 genes encode proteins, of which ∼150 were not assigned a molecular function or predicted...

Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum disorder (ASD), caused by mutation in the Fmr1 gene. In addition to cognitive and behavioral challenges, FXS patients often experience altered gut microbiome-induced gastrointestinal (GI) problems. Evidence suggests that an altered gut microbiome can disrupt mucosal barrier and promote inflammation, leading to impaired intestinal barrier integrity and function. However, the mechanisms by which the gut microbiome alters...