TY - JOUR
T1 - Clostridium scindens ATCC 35704
T2 - Integration of nutritional requirements, the complete genome sequence, and global transcriptional responses to bile acids
AU - Devendran, Saravanan
AU - Shrestha, Rachana
AU - Alves, João M.P.
AU - Wolf, Patricia G.
AU - Ly, Lindsey
AU - Hernandez, Alvaro G.
AU - Méndez-García, Celia
AU - Inboden, Ashley
AU - Wiley, J'nai
AU - Paul, Oindrila
AU - Allen, Avery
AU - Springer, Emily
AU - Wright, Chris L.
AU - Fields, Christopher J.
AU - Daniel, Steven L.
AU - Ridlon, Jason M.
N1 - Publisher Copyright:
© 2019 American Society for Microbiology.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - In the human gut, Clostridium scindens ATCC 35704 is a predominant bacterium and one of the major bile acid 7α-dehydroxylating anaerobes. While this organism is well-studied relative to bile acid metabolism, little is known about the basic nutrition and physiology of C. scindens ATCC 35704. To determine the amino acid and vitamin requirements of C. scindens, the leave-one-out (one amino acid group or vitamin) technique was used to eliminate the nonessential amino acids and vitamins. With this approach, the amino acid tryptophan and three vitamins (riboflavin, pantothenate, and pyridoxal) were found to be required for the growth of C. scindens. In the newly developed defined medium, C. scindens fermented glucose mainly to ethanol, acetate, formate, and H2. The genome of C. scindens ATCC 35704 was completed through PacBio sequencing. Pathway analysis of the genome sequence coupled with transcriptome sequencing (RNA-Seq) under defined culture conditions revealed consistency with the growth requirements and end products of glucose metabolism. Induction with bile acids revealed complex and differential responses to cholic acid and deoxycholic acid, including the expression of potentially novel bile acid-inducible genes involved in cholic acid metabolism. Responses to toxic deoxycholic acid included expression of genes predicted to be involved in DNA repair, oxidative stress, cell wall maintenance/metabolism, chaperone synthesis, and downregulation of one-third of the genome. These analyses provide valuable insight into the overall biology of C. scindens which may be important in treatment of disease associated with increased colonic secondary bile acids.
AB - In the human gut, Clostridium scindens ATCC 35704 is a predominant bacterium and one of the major bile acid 7α-dehydroxylating anaerobes. While this organism is well-studied relative to bile acid metabolism, little is known about the basic nutrition and physiology of C. scindens ATCC 35704. To determine the amino acid and vitamin requirements of C. scindens, the leave-one-out (one amino acid group or vitamin) technique was used to eliminate the nonessential amino acids and vitamins. With this approach, the amino acid tryptophan and three vitamins (riboflavin, pantothenate, and pyridoxal) were found to be required for the growth of C. scindens. In the newly developed defined medium, C. scindens fermented glucose mainly to ethanol, acetate, formate, and H2. The genome of C. scindens ATCC 35704 was completed through PacBio sequencing. Pathway analysis of the genome sequence coupled with transcriptome sequencing (RNA-Seq) under defined culture conditions revealed consistency with the growth requirements and end products of glucose metabolism. Induction with bile acids revealed complex and differential responses to cholic acid and deoxycholic acid, including the expression of potentially novel bile acid-inducible genes involved in cholic acid metabolism. Responses to toxic deoxycholic acid included expression of genes predicted to be involved in DNA repair, oxidative stress, cell wall maintenance/metabolism, chaperone synthesis, and downregulation of one-third of the genome. These analyses provide valuable insight into the overall biology of C. scindens which may be important in treatment of disease associated with increased colonic secondary bile acids.
KW - Bile acid
KW - Clostridium scindens
KW - Defined medium
KW - Deoxycholic acid
KW - Growth factor requirements
KW - RNA-Seq
UR - http://www.scopus.com/inward/record.url?scp=85063693576&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063693576&partnerID=8YFLogxK
U2 - 10.1128/AEM.00052-19
DO - 10.1128/AEM.00052-19
M3 - Article
C2 - 30737348
AN - SCOPUS:85063693576
SN - 0099-2240
VL - 85
JO - Applied and environmental microbiology
JF - Applied and environmental microbiology
IS - 7
M1 - e00052-19
ER -