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Transcript
The Gram-Negative Bacilli of
Medical Importance 1/2
Professor Sudheer Kher
1
Learning Objectives
1.
2.
3.
4.
5.
6.
Enlist medically important GNBs
Explain the basis of classification of GNBs
General properties of enterobacteriaceae
Discuss the role of toxins and other virulence
factors in pathogenesis
Describe the mechanism of action of various
toxins6.
List pathogenicity
Resources - Ananthnarayan
2
Representative Gram-negative Bacilli
1. Gram-negative rods
a. Family Enterobacteriaceae
Medically important species

Escherichia coli,

Salmonella enterica,
Shigella, Klebsiella spp,

Proteus spp
b. Pseudomonas spp related
Organisms

2. Curved rods
• Vibrio spp
• Campylobacter spp
• Helicobacter spp

3.Miscellaneous



Legionella spp
Chlamydia spp
Rickeettsia
c. Bordetella pertussis
d. Haemophilus spp
3
Septic Shock-Endotoxic shock
 LPS
Release of LPS as bacteria
breaks apart
(lipopolysacchardide)
Component of Gram
negative cell wall is a
potent immune
stimulant.
 May lead to circulatory
failure, tissue damage
and death
4
5
Aerobic Gram-Negative Bacilli
 Pseudomonas
– an opportunistic
pathogen
 Brucella & Francisella – zoonotic
pathogens
 Bordetella & Legionella – mainly human
pathogens
6
Pseudomonas
 small
gram-negative rods with a single
polar flagellum, produce oxidase &
catalase
 highly versatile metabolism
7
Pseudomonas aeruginosa

common inhabitant of soil & water (ubiquitous-wide
spread)






intestinal resident in 10% normal people
grapelike odor
greenish-blue pigment (pyocyanin)
resistant to soaps, dyes, quaternary
ammonium disinfectants, drugs, drying
frequent contaminant of ventilators, IV
solutions, anesthesia equipment
opportunistic pathogen
8
Pseudomonas aeruginosa







common cause of nosocomial infections in hosts
with burns, neoplastic disease, cystic fibrosis
Can cause: pneumonia, UTI, abscesses
Septicemia can lead to: endocarditis, meningitis,
bronchopneumonia
Corneal ulcers from contaminated lens solutions
Ear infections (Otitis) “swimmer’s ear”
Skin rash (contaminated hot tubs, saunas,
swimming pools)
multidrug resistant
9
Brucella

tiny gram-negative coccobacilli
 2 species







Brucella abortus (cattle)
Brucella suis (pigs)
Brucellosis (synonyms=malta fever, undulant
fever, & Bang disease) – a zoonosis transmitted to
humans from infected animals
fluctuating pattern of fever –weeks to a year
combination of tetracycline & rifampin or
streptomycin
animal vaccine available (efforts underway to
eradicate from cattle herds and swine)
10
potential bioweapon
Brucellosis
Undulating fever 11
Francisella tularensis








causes tularemia, a zoonotic disease of mammals
endemic to the northern hemisphere, particularly
rabbits
transmitted by contact with infected animals,
water & dust or bites by vectors
headache, backache, fever, chills, malaise &
weakness
10% death rate in systemic & pulmonic forms
intracellular persistence can lead to relapse
gentamicin or tetracycline
attenuated vaccine available
potential bioterrorism agent
12
Bordetella pertussis







minute, encapsulated coccobacillus
causes pertussis or whooping cough, a
communicable childhood affliction
acute respiratory syndrome
often severe, life-threatening complications in
babies
reservoir – apparently healthy carriers
transmission by direct contact or inhalation of
aerosols
May be relatively common in adults (as
chronic cough) and be misdiagnosed as a
cold or the flu
13
Bordetella pertussis

virulence factors


receptors that recognize & bind to ciliated
respiratory epithelial cells
toxins that destroy & dislodge ciliated cells

loss of ciliary mechanism leads to buildup of
mucus & blockage of the airways
 Hacking coughs followed by abrupt deep
inhalation (whoop)
 Vaccine does not give long-term immunity so
adults and older children can have a
recurrence
14
Time course
15
Legionella pneumophilia
16
Legionella pneumophila







widely distributed in water
live in close association with amebas
1976 epidemic of pneumonia afflicted 200
American Legion members attending a
convention in Philadelphia & killed 29 (source
was a contaminated air-conditioning system)
Legionnaires disease
Most prevalent in males over 50
nosocomial disease in elderly patients
Symptoms: fever, cough, diarrhea, abdominal
pain, pneumonia fatality rate of 3-30%
azithromycin
17
Enterobacteriaceae Family









Large family of gram-negative non sporing rods, motile / non motile
Reduce nitrates to nitrites
Catalase positive
Oxidase negative
Do not produce pigments.
many members inhabit soil, water, & decaying matter & common
occupants of large bowel of humans & animals
facultative anaerobes, grow best in air
Cause diarrhea through enterotoxins
Divided into coliforms (lactose fermenters) and non-coliforms (non
lactose fermenters)
18
Diarrheal Disease

Two Mechanisms

Toxigenic
• Organism itself does not invade the tissue
• Enterotoxins released which cause cells to increase
secretion secretory diarrhea

Invasive
• Microbes breakdown epithelial cells and form ulcerations.
May see bleeding


Fluid and electrolyte loss may result in
dehydration…death.
Diarrheal disease = 40% of infectious diseases
 18% of death worldwide
19
Nosocomial
Infections
Nosocomial
infections from
Gram negative
enterics
20
Coliforms- Ferment lactose. (normal enteric flora but may
cause infections)
Noncoliforms- Do not ferment lactose. (some are normal
enteric flora others are true pathogens…Salmonella, Shigella)
21
Escherichia coli

most common aerobic & non-fastidious
bacterium in gut
 enterotoxigenic E. coli causes severe diarrhea
due to heat-labile toxin & heat-stable toxin –
stimulate secretion & fluid loss; also has fimbrae
 enteroinvasive E. coli causes inflammatory
disease of the large intestine
 enteropathogenic E. coli linked to wasting form
infantile diarrhea; O157:H7 strain causes
hemorrhagic syndrome & kidney damage
22
Escherichia coli
 pathogenic
strains frequent agents of
infantile diarrhea – greatest cause of
mortality among babies
 causes ~70% of traveler’s diarrhea
 causes 50-80% UTI
 indicator of fecal contamination in water
23
E. coli O157:H7
• 70,000 cases annually
• Bloody diarrhea, hemorrhagic colitis,
hemolytic uremic syndrome
• Displaces normal, harmless strains in
Intestines
• Produces shiga-like toxin (kills host cells)
24
Other coliforms

Klebsiella pneumoniae– normal inhabitant of
respiratory tract, has large capsule, cause of
nosocomial pneumonia, mennigitis, bacteremia,
wound infections & UTIs
 Enterobacter – UTIs, surgical wounds
 Serratia marcescens – produces a red pigment;
causes pneumonia, burn & wound infections,
septicemia & meningitis
 Citrobacter – opportunistic UTIs & bacteremia
25
Capsule of Klebsiella pneumoniare
26
Noncoliform lactose-negative
enterics
 Proteus
 Salmonella
& Shigella
27
Proteus


Swarm on surface of moist agar in a concentric
pattern
Cause UTI, wound infections, pneumonia,
septicemia, & infant diarrhea
28
Salmonella
typhi & S. paratyphi A, B, C – typhoid
fever – ingested bacilli adhere to small
 S.
intestine, cause invasive diarrhea that leads to
septicemia. Asymptomatic carriers perpetuate
and spread the bacteria.
enteritidis – 1,700 serotypes (varieties)salmonellosis – can be zoonotic (fecal
 S.
contamination of food products) (1/3 of all chickens have
Salmonella)

Food Poisoning-gastroenteritis for 2-5 days
29
Phases of
Typhoid Fever
Invasion
Septicemia
30
Typhoid Mary
31
Shigella
Shigellosis – bacillary dysentery
•S. dysenteriae, S. sonnei, S. flexneri & S. boydii
•Invades large intestine, can perforate intestine or invade
blood (septicemia)
•Virulence factors: endotoxin & exotoxins
•Treatment – fluid replacement & in complicated cases
ciprofloxacin & sulfa-trimethoprim
Patches of mucus and blood
32
33