Virulence Factor Of E. Coli 2r5f47

Virulence Factors of E. coli

Nazish Baig BSBT - 02113028

CONTENTS • • • • • • • • • •

What is E. coli? Types of E. coli Virulence of E. coli Epidemiology Virulence genotype Adhesins Virulence genes Serum Resistance protein Siderophores Toxin and Proteases Summary

WHAT IS Escherichia coli?

• Enterobacteriaceae family • Gram Negative and rod shaped and normal flora • Remain unaffected – No virulent gene • Become virulent and cause disease – Bacteriophage – Plasmid DNA encode enterotoxins – Virulence factors invasion

TYPES OF E. coli

• Six pathotypes 1.

Enteroaggregative E. coli (EAEC)

2.

Enteroinvasive E. coli (EIEC)

3.

Enterohemorrhagic E. coli (EHEC)

4.

Enteropathogenic E. coli (EPEC)

5.

Enterotoxigenic E. coli (ETEC)

6.

Diffusely adherent E. coli (DAEC)

DAEC

EPEC

EHEC EAEC ETEC

EIEC

Shows Venn diagram demonstrating relationship of diarrheal disease causing E. coli

EPIDIMOLOGY

• Most common illness in the world. • More than 30 countries reported infection. – Canada, US and Scotland in 1996 • According to WHO (2005) – 2 million death annually

VIRULENCE FACTOR??

VIRULENCE FACTOR

• The word ‘virulence factor’ is used for causes or factors that has a major influence to a pathogenic strain of E. coli

Promotes

Proliferation

Colonization

Interaction

“TYPE OF VIRULENCE FACTORS”

There are two main types of virulence factors of E. coli

Type 1 fimbriae

Surface virulence factors LPS P fimbrial

(lipopolysacch aride)

S and F1C fimbriae

Exported virulence factors Toxins (RTX)

Haemolysin (HlyA)

cytotoxic necrotizing factor (CNF)

siderphore s

iron molecules

Genotype

• 15 categories of virulent gene for E. coli • Adhesins (papA, papG, fimH), • Dr – binding adhesins (afa/draBC) • S and F1C fimbriae (sfa/focDE) • Toxins (HlyA, CNF) • Serum resistance gene (traT, iss) • Siderophores (iroA, iutA) • Polysaccharide coating (LPS)

SURFACE VIRULENCE

Adhesins • Adherence of bacterium with host

cell allow them – To colonize the tissue. – To bind to host cells • fimbriae (pili) • some bacterial cell walls • Capsules

• These adhesins bind to specific epithelium receptors

•

Type 1 fimbriae P fimbriae S fimbriae Afimbrial adhesins

• FimH, FimA • D – mannose – sensitive • type 1 – fimbriae to or attach with various cells, such as, epithelial cells, erythrocytes, mast cells, granulocytes macrophages

• papG, papA, papC • P – fimbrial (papG) contain two alleles; alleles II and III • Gal (al– 4) Gal • Pilus assembly; central region of pap operon

• sfa/foc • Central region of sfa (S fimbriae) and foc (F1C fimbriae) operons

• Adhesion to mucosal epithelium and tissue matrix, cytokine induction • Central region of Dr antigen–specific fimbrial and afimbrial adhesin operons • Dr/afa

Afimbriated Bacterial Cells

Non-adherent Afimbriated Bacterial Cells and Buccal Cells

Fimbriated Bacterial Cells

Plasmid-Associated Proteins in Serum Resistance

• Defense mechanism of host against invasion of foreign particles. • Virulent effect on Gram negative bacteria. • E. coli virulence factors like – Co1V plasmid-encoded proteins Iss and traT that assist in bacterial resistance. traT gene

• traT weighing 25kDa • Surface exclusion, serum survival

Iss gene

• Iss is a protein weighing 10-11kDa • anti-complimentary effect

EXPORTED VIRULENCE

Siderophores

• Enterobactin, a generally known siderophore is encoded by cluster of ‘ent gene’ • Receptor FepA • Host protein lipocalin 2 is produced by host. • iroA gene is carried by many UPEC isolates within PAIs. • Iuc (aerobactin gene cluster) and iutA (ferri-aerobatin) virulence of these strains is decided by expression of the iron uptake system.

Conti..

Toxins and Proteases • Inactivate one or more vital component of the host. • Produce Exotoxins • Hemolysins, Enterotoxins causes Diarrheas, • Important toxins – Heat labile HL Heat stable HS – Vero toxins VT – Shigella toxins ST

Haemolysin (hly)

• Lyses red blood cells and attacks immune systems of host, badly impairing the function of cells. • Type of haemolysin, – alpha haemolysin – beta haemolysin – gamma haemolysin

Four types of Hemolysin genes;

Hemolysin genes Hly A

Hly B

Hly C

Hly D

programs the structure of haemolysin protein

gives energy during the process

activates hlyA, so enable binding with erythrocytes

release of haemolysin from the outer membrane

Hemolysin genes

Cytotoxic necrotizing factor (CNF Toxin)

• CNFs starts necrosis and stimulate the formation of multinucleated cells • Almost 5 % to 30% causes diarrhea • Perform its function by the activation of Rho, • Encodes cnf gene • Two domains of CNF toxins: – cell binding domain – catalytic domain.

Surface Coating

• Surface coating E. coli

LPS ( lipopolysacch aride)

O– antigens

K – antigens (capsular polysaccharides)

• Responsible for the virulence factors in the extraintestinal infections.

Summary • E. coli is the most common and prevailing gram negative bacteria mostly found in human fecal. Some theories on pathogenicity suggests that distinct properties which enables the E. coli to overwhelmed the host defense in new environment that is needed to escape the restriction of the colonic mileu, moves in the new niches • Virulence factors help to discriminate or characterize the potential of pathogens from normal strains • In this presentation we summarized the current position of knowledge about the genetics, mechanisms of action, and clinical significance of the VFs thought to be most important in E. coli.