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Clostridium sordellii outer spore proteins maintain spore structural integrity and promote bacterial clearance from the gastrointestinal tract.

ABSTRACT: Bacterial spores play an important role in disease initiation, transmission and persistence. In some species, the exosporium forms the outermost structure of the spore and provides the first point of contact between the spore and the environment. The exosporium may also be involved in spore adherence, protection and germination. Clostridium sordellii is a highly lethal, spore forming pathogen that causes soft-tissue infections, enteritis and toxic-shock syndrome. Despite the importance of C. sordellii spores in disease, spore proteins from this bacterium have not been defined or interrogated functionally. In this study, we identified the C. sordellii outer spore proteome and two of the identified proteins, CsA and CsB, were characterised using a genetic and phenotypic approach. Both proteins were essential for the correct formation and positioning of the C. sordellii spore coat and exosporium. The absence of CsA reduced sporulation levels and increased spore sensitivity to heat, sodium hydroxide and hydrochloric acid. By comparison, CsB was required for normal levels of spore adherence to cervical, but not vaginal, cells, with csB mutant spores having increased adherence properties. The establishment of a mouse infection model of the gastrointestinal tract for C. sordellii allowed the role of CsA and CsB to be interrogated in an infected host. Following the oral administration of spores to mice, the wild-type strain efficiently colonized the gastrointestinal tract, with the peak of bacterial numbers occurring at one day post-infection. Colonization was reduced by two logs at four days post-infection. By comparison, mice infected with the csB mutant did not show a reduction in bacterial numbers. We conclude that C. sordellii outer spore proteins are important for the structural and functional integrity of spores. Furthermore, outer spore proteins are required for wild-type levels of colonization during infection, possibly as a result of the role that the proteins play in spore structure and morphology.

SUBMITTER: Rabi R

PROVIDER: S-EPMC5927469 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Clostridium sordellii outer spore proteins maintain spore structural integrity and promote bacterial clearance from the gastrointestinal tract.

Rabi Rebecca R Larcombe Sarah S Mathias Rommel R McGowan Sheena S Awad Milena M Lyras Dena D

PLoS pathogens 20180418 4

Bacterial spores play an important role in disease initiation, transmission and persistence. In some species, the exosporium forms the outermost structure of the spore and provides the first point of contact between the spore and the environment. The exosporium may also be involved in spore adherence, protection and germination. Clostridium sordellii is a highly lethal, spore forming pathogen that causes soft-tissue infections, enteritis and toxic-shock syndrome. Despite the importance of C. sor ...[more]

PMID: 29668758

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Project description:Bacterial spores play an important role in disease initiation, transmission and persistence. The outermost spore layer, the exosporium, is important as it is the first point of contact between the spore and the environment and may be involved in spore adherence, protection and germination. Clostridium sordellii is a highly lethal, spore forming pathogen that causes soft-tissue infections, enteritis and toxic-shock syndrome. Despite the importance of C. sordellii spores in disease, spore proteins from this bacterium have not been defined or interrogated functionally. In this study, we identified the C. sordellii outer spore proteome and two of the identified proteins, CSA and CSB, were characterised using a genetic and phenotypic approach. Both proteins were essential for the correct formation and positioning of the C. sordellii spore coat and exosporium. The absence of CSA reduced sporulation levels and increased spore sensitivity to heat, sodium hydroxide and hydrochloric acid. By comparison, CSB was required for normal levels of spore adherence to cervical, but not vaginal, cells, with csb mutant spores having increased adherence properties. The establishment of a mouse infection model of the gastrointestinal tract for C. sordellii allowed the role of CSA and CSB to be interrogated in an infected host. Following the oral administration of spores to mice, the wild-type strain efficiently colonized the gastrointestinal tract, with the peak of bacterial numbers occurring at one day post-infection. Colonization was reduced by two logs at four days post-infection. By comparison, mice infected with the csb mutant did not show a reduction in bacterial numbers. The absence of CSB therefore allows the csb mutant to persist within the gastrointestinal tract. We conclude that C. sordellii outer spore proteins are important for the structural and functional integrity of spores, and for colonization and persistence during infection. Finally, Clostridium difficile, Bacillus cereus and Bacillus anthracis encode proteins with homology to CSA and CSB but these bacteria produce spores that are structurally dissimilar to those of C. sordellii, and the function of the proteins in these hosts is different to that in C. sordellii. These findings suggest that, despite their homology, spore proteins can have variable functions in different bacterial species which highlights the necessity of studying each spore protein in the cognate species from which it originates.

Project description:Uranium-bearing respirable dust can cause various health problems, such as cardiovascular and neurological disorders, cancers, immunosuppression, and autoimmunity. Exposure to elevated levels of uranium is linked to many such health conditions in Navajo Nation residents in northwestern New Mexico. Most studies have focused on the fate of inhaled dust particles (<4 μm) in the lungs. However, larger-sized inhaled particles (10-20 μm) can be cleared to the human gastrointestinal tract (GIT), thereby enabling them to interact with stomach and intestinal fluids. Despite the vital importance of understanding the fate of uranium-bearing solids entering the human GIT and their impact on body tissues, cells, and gut microbiota, our understanding remains limited. This study investigated uranium solubility from dust and sediment samples collected near two uranium mines in the Grants Mining District in New Mexico in two simulated gastrointestinal fluids representing fasting conditions in the GIT: Simulated Gastric Fluid (SGF) and Simulated Intestinal Fluid (SIF). The dissolution of uranium from dust depends on its mineralogy, fluid pH, and composition. The dust samples from the Jackpile mine favored higher solubility in the SIF solution, whereas the sediment samples from the St. Anthony Mine favored higher solubility in the SGF solution. Further, geochemical calculations performed with the PHREEQC modeling program suggested that samples rich in the minerals andersonite, tyuyamunite, and/or autunite have higher uranium dissolution in the SIF solution than in the SGF solution. We also tested the effect of added kaolinite and microcline, which are both present in some samples. The ratio of dissolved uranium in SGF relative to SIF decreases with the addition of kaolinite for all mineral phases but andersonite. With the addition of microcline, the ratio of dissolved uranium in SGF relative to SIF decreases for all the tested uranium minerals. The most prevalent oxidation state of dissolved uranium was computationally determined as +6, U(VI). The geochemical calculations made with PHREEQC agree with the experimentally observed results. Therefore, this study gives insight into the mineralogy-controlled toxicological assessment of uranium-containing inhaled dust cleared to the gastrointestinal tract.

Dataset Information

Clostridium sordellii outer spore proteins maintain spore structural integrity and promote bacterial clearance from the gastrointestinal tract.

Publications

Clostridium sordellii outer spore proteins maintain spore structural integrity and promote bacterial clearance from the gastrointestinal tract.

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