Interspecies Microbial Fusion and Large-Scale Exchange of Cytoplasmic Proteins and RNA in a Syntrophic Clostridium Coculture

Abstract

Microbial syntrophy is universal in nature, profoundly affecting the composition and function of microbiomes. We have recently reported data suggesting direct cell-to-cell interactions leading to electron and material exchange between the two microbes in the syntrophy between Clostridium ljungdahlii and C. acetobutylicum. Here, transmission electron microscopy and electron tomography demonstrated cell wall and membrane fusions between the two organisms, whereby C. ljungdahlii appears to invade C. acetobutylicum pole to pole. Correlative fluorescence transmission electron microscopy demonstrated large-scale exchange of proteins. Flow cytometry analysis captured the extent and dynamic persistence of these interactions. Dividing hybrid cells were identified containing stained proteins from both organisms, thus demonstrating persistence of cells with exchanged cellular components. Fluorescence microscopy and flow cytometry of one species with stained RNA and the other tagged with a fluorescent protein demonstrated extensive RNA exchange and identified hybrid cells, some of which continued to divide, while some were in an advanced C. acetobutylicum sporulation form. These data demonstrate that cell fusion enables large-scale cellular material exchange between the two organisms. Although unanticipated and never previously reported, these phenomena are likely widely distributed in nature, have profound implications for species evolution and the function of microbial communities, and could find utility in biotechnology. They may shed new light onto little-understood phenomena, such as antibiotic heteroresistance of pathogens, pathogen invasion of human tissues, and the evolutionary trajectory and persistence of unculturable bacteria. IMPORTANCE We report that two different bacterial organisms engage in heterologous cell fusion that leads to massive exchange of cellular material, including proteins and RNA, and the formation of persistent hybrid cells. The interspecies cell fusion observed here involves a syntrophic microbial system, but these heterologous cell fusions were observed even under nonstrict syntrophic conditions, leaving open the possibility that strict syntrophy may not be necessary for interspecies cell fusion and cellular material exchange. Formation of hybrid cells that contain proteins and RNA from both organisms is unexpected and unprecedented. Such fusion events are likely widely distributed in nature, but have gone undetected. The implications are profound and may shed light onto many unexplained phenomena in human health, natural environments, evolutionary biology, and biotechnology.

Origins of eukaryotic excitability

“…Among cells of the spirochaete Borrelia , frequent outer membrane fusion and occasional inner membrane fusion were observed [ 106 ]. A recent study reported complete interspecies cell–cell fusion with large-scale exchange of cellular components between the bacteria Clostridium ljungdahlii and Clostridium acetobutylicum [ 107 ].…”

A scale-free, fully connected global transition network underlies known microbiome diversity

“…Here we describe the compositional dynamics and variation among microbial communities by a microbiome transition model. In this model, a microbial community is essentially a combination of microorganisms, and the structure of a community can be modified to another form by adding and/or removing species by compositional dispersal or fusion [8, 9] ( Fig. S1 ).…”

Challenges and Perspective in Integrated Multi-Omics in Gut Microbiota Studies

“…Also, since there is no standardized method for sample preparation for metatproteomic analysis, similar studies may yield varying results [ 51 , 52 ]. Furthermore, not all the detected microbial proteins may be present in the protein database being use for the identification [ 53 ] and this can limit the number of peptides identified in a given sample. Meanwhile, there are still many microbial proteins that have not been characterized and have no known functions [ 54 , 55 ] and this can make it difficult to make sense of such data during metaproteomic analysis.…”