E. Coli Pathogenesis and Antimicrobial Therapy

E. COLI PATHOGENESIS AND ANTIMICROBIAL THERAPY

OUTLINE

• I INTRODUCTION
• E. coli characteristics
• E. coli serotypes
• Genes & becoming a pathogen
• II E.coli PATHOGENESIS
• Enteropathogenic E.coli
• Enterotoxigenic E.coli
• Extraintestinal infections
• Role in colorectal cancer
• III ANTIMICROBIAL RESISTANCE
• Importance & how it is developed
• B-lactam antibiotics
• Quimiotherapeutic agents
• IV POSSIBLE ANTIMICROBIAL THERAPIES
• Difficulties
• Antibiograms
• Possible drugs
• Phage therapy

ANTIMICROBIAL THERAPY

INTRODUCTION

GENES AND PATHOGEN

CHARACTERISTICS

E. coli genome

• Conserved group
• Flexible group
• Provide specific properties
• Acquire virulence
• Gain or loss of genes

DIFFICULTIES

7000 genes

3500 genes

ANTIBIOGRAMS

• Rod-shaped
• Outer membrane
• Intestine of mammals
• 100 ufc/g
• Indicator fecal contamination

• E. coli more resistant to antibiotics than gram-positives
• Amoxicilin and cephalosporin
• Antibiotic resistance
• What can we do?
• Major problem: selecting a good therapy method

• Overall, no current treatment for E. coli infections
• Antibiogram show what could be the best agent for treatment
• Susceptibility to different antibiotics
• Location of infection
• Severe?

SEROTYPES

• Most strains are harmless
• Infectious E.coli: Antigen
• O (outer membrane)
• K (capsule)
• H (flagellum)

Cause serious intestinal infections

PHAGE THERAPY

POSSIBLE DRUGS

• Studies of drugs against beta-lactamase (resistant) E. coli
• Carbapenem
• Some developed carbapenemase activity!
• Nitrofuratoin: treatment for Urinary Tract Infections

• USA used enterobacteria phage T4 to treat diarrhea caused by EPEC
• Cheap
• Does not depend on antibiotics
• Very specific

Carbapenem

Antimicrobial Resistance

Fluoroquinones

Quimiotherapeutic against DNA gyrase

Importance

Pathogenesis

• Increase

Gram-

-Humans overuse

-Feeding animals

Resistance

Possible role in colorectal cancer

Efflux pumps

Trimethoprim-sulfamethoxazole

PKS(Polyketide synthase )

Normal concentration

ExPEC

Plasmid

The most resistant strain to antibiotics

Damage DNA

-Calibactrin

• Enteropathogenic E. coli

Used in urinary infections

plasmid

High concentration

Mutation

Extraintestinal infections

Resistance

Alteration substrate enzymes

ExPEC

Neonatal meningitis

Decreases cell pemeability

-NMEC

• K1 Capsule

Penetrate cerebrospinal fluid

Invade blood-brain-barrier

Urinary infections

Cellulitis

P fimbrae

• Inner infection of tissues

Uropathogenic E. Coli

Symptoms

Dr Family adhesines

Symptoms

How?

• Fever

ß-lactam antibiotics

• Inflamation

Conjugation

-Diarrhea

-Fever

-Vomits

-Dehydratation

-Main drug in infection treatment

• Aminopenicillins
• Cephalosporins

Resistance

• ß-lactamases

• E.coli enterotoxigenic(ETEC)

• Traveller´s diarrhea

-Attack digestive tract

-Overpower defense mechanism

• Diagnosis

LT

Enterotoxins

ST

PCR

Guillermo Lendrino

Irene Sanz