Identification of a Novel Lipoprotein Regulator of Clostridium difficile Spore Germination

PLoS Pathogens
Kelly A FimlaidAimee Shen

Abstract

Clostridium difficile is a Gram-positive spore-forming pathogen and a leading cause of nosocomial diarrhea. C. difficile infections are transmitted when ingested spores germinate in the gastrointestinal tract and transform into vegetative cells. Germination begins when the germinant receptor CspC detects bile salts in the gut. CspC is a subtilisin-like serine pseudoprotease that activates the related CspB serine protease through an unknown mechanism. Activated CspB cleaves the pro-SleC zymogen, which allows the activated SleC cortex hydrolase to degrade the protective cortex layer. While these regulators are essential for C. difficile spores to outgrow and form toxin-secreting vegetative cells, the mechanisms controlling their function have only been partially characterized. In this study, we identify the lipoprotein GerS as a novel regulator of C. difficile spore germination using targeted mutagenesis. A gerS mutant has a severe germination defect and fails to degrade cortex even though it processes SleC at wildtype levels. Using complementation analyses, we demonstrate that GerS secretion, but not lipidation, is necessary for GerS to activate SleC. Importantly, loss of GerS attenuates the virulence of C. difficile in a hamste...Continue Reading

References

Mar 1, 1989·Journal of Medical Microbiology·S KamiyaS Nakamura
Dec 24, 1996·Proceedings of the National Academy of Sciences of the United States of America·D L PophamP Setlow
Dec 3, 1999·Letters in Applied Microbiology·R G Leuschner, P J Lillford
Sep 15, 2000·Journal of Bacteriology·M PaidhungatP Setlow
May 24, 2001·The Journal of Infectious Diseases·S P SambolD N Gerding
Dec 10, 2003·Current Opinion in Microbiology·Peter Setlow
Mar 24, 2004·Nature Reviews. Microbiology·Jeff Errington
Feb 25, 2006·Journal of Molecular Biology·Stephanie T WangPatrick Eichenberger
Nov 24, 2006·Journal of Bacteriology·Patricia L PelczarPeter Setlow
Dec 14, 2006·Archives of Microbiology·Xiaohua YanHuarong Tan
Apr 11, 2007·Bioscience, Biotechnology, and Biochemistry·Toshihiko KumazawaRyuichi Moriyama
Jul 31, 2007·Journal of Microbiological Methods·John T HeapNigel P Minton
Aug 30, 2007·Molecular Microbiology·Sean S DineenAbraham L Sonenshein
Feb 5, 2008·Journal of Bacteriology·Joseph A Sorg, Abraham L Sonenshein
Jun 17, 2008·Journal of Bacteriology·Patricia L Pelczar, Peter Setlow
Oct 31, 2008·The New England Journal of Medicine·Ciarán P Kelly, J Thomas LaMont
Dec 9, 2008·Trends in Microbiology·Matthew I HutchingsIain C Sutcliffe
Feb 24, 2009·Current Protocols in Microbiology·Joseph A Sorg, Sean S Dineen
Apr 1, 2009·Microbiology·Wiyada MongkolthanarukAnne Moir
May 19, 2009·Journal of Microbiological Methods·John T HeapNigel P Minton
Jun 17, 2009·Nature Reviews. Microbiology·Maja RupnikDale N Gerding
May 4, 2010·Journal of Bacteriology·Xuan Yi, Peter Setlow
Jul 9, 2010·Clinical Microbiology Reviews·J FreemanM H Wilcox
Oct 26, 2010·Journal of Bacteriology·Amber HowertonErnesto Abel-Santos
Nov 30, 2010·Trends in Microbiology·Daniel Paredes-SabjaMahfuzur R Sarker
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Feb 4, 2011·The New England Journal of Medicine·Thomas J LouieUNKNOWN OPT-80-003 Clinical Study Group

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Citations

Jul 29, 2016·PloS One·Brintha Parasumanna GirinathanRevathi Govind
Nov 12, 2016·Frontiers in Microbiology·Adrianne N EdwardsShonna M McBride
Jul 14, 2017·PLoS Pathogens·Travis J KochanPhilip C Hanna
Apr 6, 2018·PLoS Genetics·Ognjen SekulovicAndrew Camilli
Feb 24, 2018·Frontiers in Cellular and Infection Microbiology·Duolong ZhuXingmin Sun
Sep 7, 2017·Journal of Bacteriology·Yuzo Kevorkian, Aimee Shen
Jul 20, 2016·Journal of Bacteriology·Disha BhattacharjeeJoseph A Sorg
Jun 19, 2016·Applied and Environmental Microbiology·Christopher J DoonaPeter Setlow
Aug 15, 2018·Journal of Applied Microbiology·Peter Setlow
Aug 31, 2016·Nature Reviews. Microbiology·Michael C AbtEric G Pamer
Sep 6, 2019·Nature Reviews. Microbiology·Boris MacekIvan Mijakovic
Jul 13, 2017·Annual Review of Microbiology·Peter SetlowYong-Qing Li
May 11, 2017·The Journal of Biological Chemistry·Ritu ShresthaJoseph A Sorg
May 16, 2018·Journal of Bacteriology·Travis J KochanPhilip C Hanna
Mar 27, 2021·Frontiers in Microbiology·Polina BeskrovnayaElitza I Tocheva
Dec 21, 2019·Microbiology Spectrum·Aimee ShenDaniel Paredes-Sabja
Aug 28, 2021·Antibiotics·Pei-Wen WangDar-Bin Shieh

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Methods Mentioned

BETA
RNA-Seq
Phase contrast microscopy
Phase contrast
transmission electron microscopy
lipidation
PCR
fluorescence microscopy

Software Mentioned

blast
Adobe Photoshop
NIS
psi
Elements
TargeTron

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