Biology subjects

Moyer, C. L.

Publications and source records attributed to Moyer, C. L..

7 recordsLinked to original sources

bioRxiv2023

Microbial metabolic potential of hydrothermal vent chimneys along the Submarine Ring of Fire

Hydrothermal vents host a diverse community of microorganisms that utilize chemical gradients from the venting fluid for their metabolisms. The venting fluid can solidify to form chimney structures that these microbes adhere to and colonize. These chimney structures are found throughout many different locations in the worlds oceans. In this study, comparative metagenomic analyses of microbial communities on five chimney structures from around the Pacific Ocean were elucidated focusing on the core taxa and genes that are characteristic for each of these hydrothermal vent chimneys, as well as highlighting differences among the taxa and genes found at each chimney due to parameters such as physical characteristics, chemistry, and activity of the vents. DNA from the chimneys was sequenced, assembled into contigs, annotated for gene function, and binned into metagenome-assembled genomes, or MAGs. Genes used for carbon, oxygen, sulfur, nitrogen, iron, and arsenic metabolism were found at varying abundances at each of the chimneys, largely from either Gammaproteobacteria or Campylobacteria. Many taxa had an overlap of these metabolic genes, indicating that functional redundancy is critical for life at these hydrothermal vents. A high relative abundance of oxygen metabolism genes coupled with low carbon fixation genes could be used as a unique identifier for inactive chimneys. Genes used for DNA repair, chemotaxis, and transposases were found to be at higher abundances at each of these hydrothermal chimneys allowing for enhanced adaptations to the ever-changing chemical and physical conditions encountered. IMPORTANCEThe metabolic byproducts of microorganisms that form and reside in hydrothermal vent chimneys facilitate nutrient cycling in both the hydrothermal vent ecosystem and throughout the worlds oceans. Diverse communities of microbes utilize chemicals in the venting fluid to gain energy and biomass. Here, metagenomic and amplicon sequencing was used to identify metabolism genes to better understand the metabolic potential of chimneys. The combination of genes detected in this study sheds light on hydrothermal vent chimneys community structure and metabolic potential throughout the Pacific Ocean.

microbiology↗

bioRxiv2023

Seafloor Incubation Experiments at Deep-Sea Hydrothermal Vents Reveal Distinct Biogeographic Signatures of Autotrophic Communities

The discharge of hydrothermal vents on the seafloor provides energy sources for dynamic and productive ecosystems, which are supported by chemosynthetic microbial populations. These populations use the energy gained by oxidizing the reduced chemicals contained within the vent fluids to fix carbon dioxide and support multiple trophic levels. Hydrothermal discharge is ephemeral and chemical composition of such fluids varies over space and time, which can result in geographically distinct microbial communities. To investigate the foundational members of the community, microbial growth chambers were placed within the hydrothermal discharge at Axial Seamount (Juan de Fuca Ridge), Magic Mountain Seamount (Explorer Ridge), and Kamaehuakanaloa Seamount (Hawaii hotspot). Campylobacteria were identified within the nascent communities, but different amplicon sequence variants were present at Axial and Kamaehuakanaloa Seamounts, indicating that geography in addition to the composition of the vent effluent influences microbial community development. These results provide insights to nascent microbial community structure and shed light on the development of diverse lithotrophic communities at hydrothermal vents.

microbiology↗

bioRxiv2022

Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a pan-Ebolavirus Immunotherapeutic

Intravenous administration (IV) of antiviral monoclonal antibodies (mAbs) is challenging due to limited resources for performing infusions during an ongoing epidemic. An ebolavirus therapeutic administered via intramuscular (IM) injection would reduce these burdens and allow rapid treatment of exposed individuals during an outbreak. Here, we demonstrate how MBP134, a two mAb pan-ebolavirus cocktail, reverses the course of Sudan ebolavirus (SUDV/Gulu) disease with a single IV or IM dose in non-human primates (NHPs) as far as five days post-exposure. Furthermore, we investigated the utility of adding half-life extension mutations to the MBP134 mAbs, ultimately creating a half-life extended cocktail designated MBP431. MBP431 demonstrated an extended serum half-life in vivo and offered complete or significant protection with a single IM dose delivered as a post-exposure prophylactic (PEP) or therapeutic in NHPs challenged with EBOV. These results support the use of MBP431 as a rapidly deployable IM medical countermeasure against every known ebolavirus.

microbiology↗

bioRxiv2021

Genotype-specific Features Reduce the Susceptibility of South American Yellow Fever Virus Strains to Vaccine-Induced Antibodies

The resurgence of yellow fever in South America has prompted mitigation through vaccination against the etiologic agent, yellow fever virus (YFV). Current vaccines are based on a virulent African isolate, and their capacity to induce neutralizing antibodies against the vaccine strain is widely used as a surrogate for protection. However, the sensitivity of genetically distinct South American strains to vaccine-induced antibodies is unknown. Here, we show that antiviral potency of the polyclonal antibody response in both U.S. and Brazilian vaccinees is attenuated against an emergent Brazilian strain. This reduction was attributable to genetic changes at two sites in the central domain II of the glycoprotein E, including the acquisition of an N-linked glycosylation site, which are unique to and shared among most South American YFV strains. Our findings call for a reevaluation of current approaches to YFV immunological surveillance in South America and suggest approaches for designing updated vaccines.

microbiology↗

bioRxiv2018

Human antibody cocktail deploys multiple functions to confer pan-ebolavirus protection

During the unprecedented 2013-2016 Ebola virus disease (EVD) epidemic in Western Africa and in its aftermath, the passive administration of monoclonal antibodies (mAbs) emerged as a promising treatment approach1-7. However, all antibody-based therapeutics currently in advanced development are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against divergent outbreak-causing ebolaviruses, including Bundibugyo virus (BDBV) and Sudan virus (SUDV)2,3,5,7. Here we advance MBP134, a cocktail of two broadly neutralizing human mAbs targeting the filovirus surface glycoprotein, GP, as a candidate pan-ebolavirus therapeutic. One component of this cocktail is a pan-ebolavirus neutralizing mAb, ADI-15878, isolated from a human EVD survivor8,9. The second, ADI-23774, was derived by affinity maturation of a human mAb8,9 via yeast display to enhance its potency against SUDV. MBP134 afforded exceptionally potent pan-ebolavirus neutralization in vitro and demonstrated greater protective efficacy than ADI-15878 alone in the guinea pig model of lethal EBOV challenge. A second-generation cocktail, MBP134AF, engineered to effectively harness natural killer (NK) cells afforded additional, unprecedented improvements in protective efficacy against EBOV and SUDV in guinea pigs relative to both its precursor and to any mAbs or mAb cocktails tested previously. MBP134AF is a best-in-class mAb cocktail suitable for evaluation as a pan-ebolavirus therapeutic in nonhuman primates.

microbiology↗

bioRxiv2018

Structural Basis of Broad Ebolavirus Neutralization by a Human Survivor Antibody

The structural features that govern broad-spectrum activity of broadly neutralizing, anti-ebolavirus antibodies (Abs) are currently unknown. Here we describe the first structure of a broadly neutralizing human Ab, ADI-15946, in complex with cleaved Ebola virus glycoprotein (EBOV GPCL). We find that ADI-15946 employs structural mimicry of a conserved interaction between the GP core and the glycan cap {beta}17-{beta}18 loop to inhibit infection. Both endosomal proteolysis of EBOV GP and binding of monoclonal Ab (mAb) FVM09 displace this loop, increase exposure of ADI-15946s conserved epitope and potentiate neutralization. Our work also illuminated the determinants of ADI-15946s reduced activity against Sudan virus (SUDV), and enabled rational, structure-guided engineering to enhance binding and neutralization against SUDV while retaining the parental breadth of activity.\n\nOne Sentence SummaryThe first crystal structure of a broadly active antibody against surface glycoproteins of ebolaviruses identifies a highly conserved epitope beneath the glycan cap and highlights the molecular requirements for broad ebolavirus neutralization.

immunology↗

bioRxiv2016

In situ estimates of iron-oxidation and accretion rates for iron-oxidizing bacterial mats at Loihi Seamount.

It is increasingly recognized that diffuse, hydrothermal venting is an important source of iron to the deep-sea that can influence oceanic iron dynamics and abundance. Lithotrophic Fe-oxidizing bacteria (FeOB) are dominant at diffuse hydrothermal vent sites, producing microbial iron mats that are often centimeters or more thick. At present, little is known about in situ Fe-oxidation rates, or accretion rates for iron mats. An in situ productivity chamber was developed that took advantage of the unique mineral morphotypes produced by FeOB to estimate rates of Fe-oxidation and accretion. Chambers were placed at two diffuse vents (1179 and 1300 mbsl) at L[o]ihi Seamount where they were colonized by FeOB for different amounts of time. From this analysis, it was estimated that Fe-oxidation rates could range from 8.2-51.9 x 10-6 mol {middle dot} hr-1, and that iron mats could accrete at around 2.2 cm {middle dot} yr-1. Molecular analysis indicated that the relative abundance of Zetaproteobacteria, a group of known FeOB, accounted for 80-90% of the bacteria colonizing the chambers. There was a distinct difference between populations at the 1179m site (Pohaku), and the 1300m site (North Hiolo Ridge). Microscope slides placed within the productivity chambers were colonized by different morphotypes of FeOB. The cells responsible for one common morphotype that produces a Y-shaped filament were identified as Zetaproteobacteria by use of a small subunit rRNA probe. This work confirms the importance of FeOB in the formation of chemosynthetic iron mats, and provides the first estimates for in situ Fe-oxidation rates and mat accretion rates.\n\nHighlightsO_LIAn in-situ productivity chamber was developed to estimate rates of Fe-oxidation and understand colonization patterns at chemosynthetic iron mats at L[o]ihi Seamount.\nC_LIO_LIFe-oxidation rates ranged from 8.2-51.9 x 10-6 mol {dot} hr-1, and it was estimated that the iron mats could accrete at around 2.2 cm {dot} yr-1.\nC_LIO_LIThe iron mat community was dominated by Zetaproteobacteria, whose relative abundance accounted for up to 89% of the microbial community.\nC_LIO_LIThe community membership that grew during short-term incubations reflected the community composition of nearby microbial mats.\nC_LI

microbiology↗