The CspC pseudoprotease regulates germination of Clostridioides difficile spores in response to multiple environmental signals

PLoS Genetics
Amy E RohlfingAimee Shen

Abstract

The gastrointestinal pathogen, Clostridioides difficile, initiates infection when its metabolically dormant spore form germinates in the mammalian gut. While most spore-forming bacteria use transmembrane germinant receptors to sense nutrient germinants, C. difficile is thought to use the soluble pseudoprotease, CspC, to detect bile acid germinants. To gain insight into CspC's unique mechanism of action, we solved its crystal structure. Guided by this structure, we identified CspC mutations that confer either hypo- or hyper-sensitivity to bile acid germinant. Surprisingly, hyper-sensitive CspC variants exhibited bile acid-independent germination as well as increased sensitivity to amino acid and/or calcium co-germinants. Since mutations in specific residues altered CspC's responsiveness to these different signals, CspC plays a critical role in regulating C. difficile spore germination in response to multiple environmental signals. Taken together, these studies implicate CspC as being intimately involved in the detection of distinct classes of co-germinants in addition to bile acids and thus raises the possibility that CspC functions as a signaling node rather than a ligand-binding receptor.

References

Feb 1, 1995·Microbiology·T KarasawaS Nakamura
Mar 1, 1995·Bioscience, Biotechnology, and Biochemistry·S MiyataS Makino
Dec 31, 2003·Methods in Enzymology·Thomas C Terwilliger
May 26, 2005·Protein Expression and Purification·F William Studier
Dec 14, 2006·Acta Crystallographica. Section D, Biological Crystallography·Airlie J McCoy
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Feb 5, 2008·Journal of Bacteriology·Joseph A Sorg, Abraham L Sonenshein
Dec 9, 2008·Journal of Bacteriology·Joseph A Sorg, Abraham L Sonenshein
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jong W YuYigong Shi
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Christian OttmannAndreas Schaller
Aug 31, 2010·Applied and Environmental Microbiology·Trevor D LawleyGordon Dougan
Sep 14, 2010·Current Biology : CB·Michiel J L de HoonDennis Vitkup
Nov 30, 2010·Trends in Microbiology·Daniel Paredes-SabjaMahfuzur R Sarker
Mar 21, 2012·Journal of Hospital Medicine : an Official Publication of the Society of Hospital Medicine·Erik Dubberke
May 23, 2012·Infection and Immunity·Laura J DeakinTrevor D Lawley
Jan 8, 2013·Journal of Bacteriology·Emily E PutnamAimee Shen
Feb 20, 2013·The Journal of Infectious Diseases·Amber HowertonErnesto Abel-Santos
Jul 10, 2013·Environmental Microbiology·Natalya Yutin, Michael Y Galperin
Aug 21, 2013·PLoS Genetics·Kelly A FimlaidAimee Shen
Feb 8, 2014·Gastroenterology·Robert A Britton, Vincent B Young
May 13, 2014·Trends in Microbiology·Daniel Paredes-SabjaJoseph A Sorg
Dec 24, 2014·Infection and Immunity·Mark J KoenigsknechtVincent B Young
Feb 26, 2015·The New England Journal of Medicine·Fernanda C LessaL Clifford McDonald
Jun 26, 2015·Clinical and Translational Gastroenterology·Paul Feuerstadt
Jul 16, 2015·The New England Journal of Medicine·Daniel A Leffler, J Thomas Lamont
Aug 19, 2015·Current Biology : CB·Alexander Sturm, Jonathan Dworkin
Oct 22, 2015·Annual Review of Microbiology·Casey M Theriot, Vincent B Young

❮ Previous
Next ❯

Citations

Mar 27, 2021·Frontiers in Microbiology·Polina BeskrovnayaElitza I Tocheva

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
PCR
gel filtration
phase-contrast microscopy

Software Mentioned

Genewiz
HKL2000
Autobuild
Solve
Chainsaw
Phenix
PyMOL
Resolve

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.