Presentation is loading. Please wait.

Presentation is loading. Please wait.

Virulence: Mechanisms of Gene Regulation II

Published byTeguh Sudirman Modified over 5 years ago

Similar presentations

Presentation on theme: "Virulence: Mechanisms of Gene Regulation II"— Presentation transcript:

1 Virulence: Mechanisms of Gene Regulation II
Regulating the Pathogenesis of Cholera CTX phage ToxT ctxA ctxB + CtxA CtxB

2 Cholera Pathogenesis Causative Agent
life-threatening diarrheal disease can rapidly attain epidemic proportions through inadequate sanitation Causative Agent Vibrio cholerae extracellular pathogen highly motile, uniflagellated, Gram-negative curved rod

3 survive passage through the gastric acid barrier of the stomach
To cause disease V. cholerae must: be ingested survive passage through the gastric acid barrier of the stomach colonize the upper small intestine produce & excrete toxin disseminate in a watery diarrhea

4 synthesizes virulence factors that help it reach, adhere to, &
V. cholerae synthesizes virulence factors that help it reach, adhere to, & colonize the intestinal epithelial layer the genes that encode these virulence factors are regulated by environmental stimuli unique to the host

5 mutants lacking toxin genes
CHOLERA TOXIN main virulence factor very potent PROOF mutants lacking toxin genes are less virulent

6 } CHOLERA TOXIN CTX phage A2 B ctxA ctxB A1 CtxA CtxB CtxB CtxB CtxB

7 A1 subunit enters host membrane epithelial cell cytoplasm
CHOLERA TOXIN: binds host GM1 receptor A1 subunit enters host membrane A2 A1 B A2 B intestinal lumen Receptor A1 epithelial cell cytoplasm

8 a G (GTP-binding) protein epithelial cell cytoplasm
A1 subunit modifies (ADP-ribosylation) a G (GTP-binding) protein A2 B intestinal lumen Receptor A1 GS GS ADPR epithelial cell cytoplasm

9 activates Adenylate cyclase
modified G protein activates Adenylate cyclase A1 GS ADPR cAMP AC AC cAMP cAMP active inactive AC AC AC ATP ATP ATP

10 activates protein kinase A, which activates transporters,
cAMP activates protein kinase A, which activates transporters, causing efflux of ions and water i.e., diarrhea HCO3- K+ Na+ H2O intestinal lumen H2O Na+ K+ K+ Na+ H2O H2O HCO3- P cAMP protein kinase A AC AC cAMP cAMP active inactive AC AC AC ATP ATP ATP

11 Virulence Factors involved in Colonization
i) single polar flagellum nonmotile strains are less virulent flagellar genes expressed when toxin genes are not motility used to reach site of colonization motility genes turned off colonization and toxigenic genes turned on

12 Virulence Factors involved in Colonization
(cont’d) ii) TCP (toxin colonization pilus) iii) ACF (accessory colonization factors) mutations in tcp or acf reduce colonization tcp & acf located on large pathogenicity island called TCP-ACF element

13 the synthesis of virulence factors
activation of the ToxR regulon permits the synthesis of virulence factors

14 The ToxR Regulon Signal + + Cholera toxin tcp toxT acf ctxA ctxB toxR
ToxS toxR toxS ToxR + ToxT acf ctxA ctxB toxT + tcp CtxA Cholera toxin CtxB

15 outside host low temp vibrio

16 toxR toxS transcription
is turned on at low temperature Thus, ToxR & ToxS proteins are synthesized ToxR ToxS Lo ToC + toxR toxS

17 inserted into membrane
ToxS ToxR ToxRS proteins inserted into membrane

18 host ingests vibrio high temp not yet in intestine

19 toxR toxS transcription off are no longer synthesized
at high temperature Hi ToC - toxR toxS ToxR & ToxS proteins are no longer synthesized

20 ToxRS is still in membrane However no signal is received Thus
ToxS ToxR ToxRS is still in membrane However no signal is received Thus ToxR regulon off

21 once inside the host intestine an intestinal (lumenal) signal
However once inside the host intestine an intestinal (lumenal) signal is sent to ToxR & ToxS which activates the ToxR regulon vibrio

22 Lumenal signal received ToxRS activate ToxT synthesis
ToxS ToxR toxT + ToxT ToxT autoregulates increases toxT transcription ToxS ToxR ToxT toxT + + ToxT ToxT ToxT ToxT Lots of ToxT synthesized

23 transcription of a pathogenicity island
Signal TCP-ACF element ToxS ToxR ToxT tcp toxT ToxT acf + + + ToxT ToxT also activates transcription of a pathogenicity island the TCP-ACF element

24 ToxT also regulates transcription the lysogenic CTX prophage
ctxA ToxT + CtxA ctxB CtxB CTX phage ToxT also regulates transcription of the ctxA ctxB operon carried by the lysogenic CTX prophage

25 - lumenal TCP-ACF signal pathogenicity island CTX prophage +
ToxS ToxR ToxT tcp toxT ToxT acf + + + ToxT CTX prophage ToxR ToxS ToxT Lo ToC ctxA ctxB + + toxR toxS - Hi ToC CtxA CtxB chromosomal toxR toxS operon

26 The ToxR Regulon Signal + + Cholera toxin tcp toxT acf ctxA ctxB toxR
ToxS toxR toxS ToxR + ToxT acf ctxA ctxB toxT + tcp CtxA Cholera toxin CtxB

27 The ToxR regulon stimulus = unknown (lumenal in nature) sensor = ToxS
regulator = ToxR member genes: toxT tcp acf ctxAB NOTE: ToxT (a member of the ToxR regulon) is itself a regulator that activates many ToxR regulon promoters

Download ppt "Virulence: Mechanisms of Gene Regulation II"

Similar presentations

Lecture 2, Oct 11 Important points from 10/7:

Lecture 2, Oct 11 Important points from 10/7:
The role of respiration in virulence gene expression of Vibrio cholerae HHMI 2011 Sara Fassio Dr. Claudia Häse Dr. Yusuke Minato.

The role of respiration in virulence gene expression of Vibrio cholerae HHMI 2011 Sara Fassio Dr. Claudia Häse Dr. Yusuke Minato.
Cell Communication Chapter 11:. Why do cells communicate? Regulation - cells need to control cellular processes. Environmental Stimuli - cells need to.

Cell Communication Chapter 11:. Why do cells communicate? Regulation - cells need to control cellular processes. Environmental Stimuli - cells need to.
Chapter 7 Cell Communication. Question? u How do cells communicate? u By “cellular” phones. u But seriously, cells do need to communicate for many reasons.

Chapter 7 Cell Communication. Question? u How do cells communicate? u By “cellular” phones. u But seriously, cells do need to communicate for many reasons.
CHAPTER 8 Metabolic Respiration Overview of Regulation Most genes encode proteins, and most proteins are enzymes. The expression of such a gene can be.

CHAPTER 8 Metabolic Respiration Overview of Regulation Most genes encode proteins, and most proteins are enzymes. The expression of such a gene can be.
gram-negative cause of severe diarrheal disease around 120,000 death per annum 200 known serogroups  cholera associated only with two serogroups (O1.

gram-negative cause of severe diarrheal disease around 120,000 death per annum 200 known serogroups  cholera associated only with two serogroups (O1.
Cell Communication II Chapter 15. An animal cell depends on extracellular signals to survive or divide.

Cell Communication II Chapter 15. An animal cell depends on extracellular signals to survive or divide.
CHOLERA Kate Ferriola-Bruckenstein. Cholera is an acute infection of the small intestine.

CHOLERA Kate Ferriola-Bruckenstein. Cholera is an acute infection of the small intestine.
Vibrio Cholera Michelle Ross, Kristin Roman, Risa Siegel.

Vibrio Cholera Michelle Ross, Kristin Roman, Risa Siegel.
CELL RECEPTORS AND SIGNALLING By Phil and Alex. Basics Signalling controls all aspects of cell behaviour: Growth Differentiation Metabolism 3 main types.

CELL RECEPTORS AND SIGNALLING By Phil and Alex. Basics Signalling controls all aspects of cell behaviour: Growth Differentiation Metabolism 3 main types.
Cholera Rose Lee and Ricardo Lé January 14, 2008 Rose Lee and Ricardo Lé January 14, 2008.

Cholera Rose Lee and Ricardo Lé January 14, 2008 Rose Lee and Ricardo Lé January 14, 2008.
Cell Communication AP Biology Minzenmayer.

Cell Communication AP Biology Minzenmayer.
Cell Signaling A __________________________is a series of steps by which a signal on a cell’s surface is converted into a ________________________________________________.

Cell Signaling A __________________________is a series of steps by which a signal on a cell’s surface is converted into a ________________________________________________.
Gene Regulation in Prokaryotes. Outline of Chapter 16 There are many steps in gene expression and regulation can occur at any one of them There are many.

Gene Regulation in Prokaryotes. Outline of Chapter 16 There are many steps in gene expression and regulation can occur at any one of them There are many.
Regulation of Gene Expression

Regulation of Gene Expression
Warm-Up  Why do you communicate?  How do you communicate?  How do you think cells communicate?  Do you think bacteria can communicate? Explain.

Warm-Up  Why do you communicate?  How do you communicate?  How do you think cells communicate?  Do you think bacteria can communicate? Explain.
CHAPTER 11 CELL COMMUNICATION 1. WHAT YOU SHOULD KNOW: The 3 stages of cell communication: reception, transduction, and response. How G-protein-coupled.

CHAPTER 11 CELL COMMUNICATION 1. WHAT YOU SHOULD KNOW: The 3 stages of cell communication: reception, transduction, and response. How G-protein-coupled.
1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 21 Images for Students.

1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 21 Images for Students.
MAIN IDEAS CHAPTER 11: 1. Cell communication processes share common features that reflect a shared evolutionary history. 2. Cells communicate with each.

MAIN IDEAS CHAPTER 11: 1. Cell communication processes share common features that reflect a shared evolutionary history. 2. Cells communicate with each.
Cholera.

Cholera.

Similar presentations

Ads by Google