Browsing by Author "Liu, Hualan"

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    Control of lupus nephritis by changes of gut microbiota
    Mu, Qinghui; Zhang, Husen; Liao, Xiaofeng; Lin, Kaisen; Liu, Hualan; Edwards, Michael R.; Ahmed, Sattar Ansar; Yuan, Ruoxi; Li, Liwu; Cecere, Thomas E.; Branson, David B.; Kirby, Jay L.; Goswami, Poorna; Leeth, Caroline M.; Read, Kaitlin A.; Oestreich, Kenneth J.; Vieson, Miranda D.; Reilly, Christopher M.; Luo, Xin M. (2017-07-11)
    Background: Systemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than suppressing it altogether. Results: Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Here we report a role of gut microbiota in the pathogenesis of renal dysfunction in lupus. Using a classical model of lupus nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut microbiota. Increasing Lactobacillales in the gut improved renal function of these mice and prolonged their survival. We used a mixture of 5 Lactobacillus strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an uncultured Lactobacillus sp. accounted for most of the observed effects. Further studies revealed that MRL/lpr mice possessed a “leaky” gut, which was reversed by increased Lactobacillus colonization. Lactobacillus treatment contributed to an anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production in the gut. In the circulation, Lactobacillus treatment increased IL-10 and decreased IgG2a that is considered to be a major immune deposit in the kidney of MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner. Conclusions: This work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupusassociated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.
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    Identification of genes involved in gliding motility and proteomic analysis of spore inner membrane proteins in Clostridium perfringens
    Liu, Hualan (Virginia Tech, 2014-06-12)
    Clostridium perfringens is a Gram-positive anaerobic pathogen of humans and animals. While lacking flagella, C. perfringens cells can still migrate across surfaces using a type of gilding motility that involves the formation of filaments of bacteria lined up in an end to end conformation. To discover the gene products that play a role in gliding, we developed a plasmid-based mariner transposon mutagenesis system that works effectively in C. perfringens. Twenty-four mutants with deficiency in gliding motility were identified and one gene, which encodes a homolog of the SagA cell wall-dependent endopeptidase, was further characterized. We also isolated and characterized two hypermotile variants of strain SM101. Compared to wide type cells, the hypermotile cells are longer and video microscopy of their gliding motility suggests they form long, thin filaments that move rapidly away from a colony, analogous to swarmer cells in bacteria with flagella. Whole genome sequencing analysis showed that both mutants have mutations in cell division genes. Complementation of these mutations with wild-type copies of each gene restored the normal motility phenotype. A model is presented explaining the principles underlying the hypermotility phenotype. Heat resistant spores are the major route for disease transmission for C. perfringens, which cause food poisoning. To elucidate the molecular mechanisms involved in spore germination as well as to identify attractive targets for development of germination inhibitors to kill spores, we combined 1D-SDS-PAGE and MALDI-TOF-MS/MS to map the whole spore inner membrane proteome, both from dormant and germinated spores. As the first comprehensive spore inner membrane proteome study, we identified 494 proteins in total and 119 are predicted to be membrane-associated proteins. Among those membrane-associated proteins, 71 changed at least two-fold in abundance after germination. This study provides the first comprehensive list of the spore inner membrane proteins that may be involved in germination of the C. perfringens spore and their relative levels during germination.
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    Plasmalogen Biosynthesis by Anaerobic Bacteria: Identification of a Two-Gene Operon Responsible for Plasmalogen Production in Clostridium perfringens
    Jackson, David R.; Cassilly, Chelsi D.; Plichta, Damian R.; Vlamakis, Hera; Liu, Hualan; Melville, Stephen B.; Xavier, Ramnik J.; Clardy, Jon (2021-01-15)
    Plasmalogens are vinyl ether-containing lipids produced by mammals and bacteria. The aerobic biosynthetic pathway in eukaryotes and bacteria is known, but the anaerobic pathway has remained a mystery. Here, we describe a two-gene operon (plasmalogen synthase, pis) responsible for plasmalogen production in the anaerobic bacterium Clostridium perfringens. While aerobic plasmalogen biosynthesis involves an oxidative conversion of an ether to a vinyl ether, anaerobic plasmalogen biosynthesis uses the reductive conversion of an ester to an aldehyde equivalent. Heterologous expression of the C. perfringens pis operon in E. coli conferred the ability to produce plasmalogens. The pls operon is predicted to encode a multidomain complex similar to benzoyl-CoA reductase/hydroxylacyl-CoA dehydratase (BCR/HAD) enzymes. Versions of this operon can be found in a wide range of obligate and facultative anaerobic bacteria, including many human gut microbes.