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The Gram-Negative Bacteria of Medical Importance. Chapter 20. Gram Negative Bacteria. Cocci. Family Neisseriaceae. Gram-negative cocci Residents of mucous membranes of warm-blooded animals Genera include Neisseria , Moraxella , Acinetobacter 2 primary human pathogens

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family neisseriaceae
Family Neisseriaceae
  • Gram-negative cocci
  • Residents of mucous membranes of warm-blooded animals
  • Genera include Neisseria, Moraxella, Acinetobacter
  • 2 primary human pathogens
    • Neisseriagonorrhoeae
    • Neisseriameningitidis
  • Gram-negative, bean-shaped, diplococci
  • No flagella or spores
  • capsules on pathogens
  • pili
  • Strict parasites, do not survive long outside of the host
  • Aerobic or microaerophilic
  • Pathogenic species require enriched complex media and CO2
neisseria gonorrhoeae
  • Causes gonorrhea, an STD
  • Virulence factors: pili, other surface molecules, IgA protease
  • Strictly a human infection
  • In top 5 STDs
  • Does not survive more than 1-2 hours on fomites
  • Infection is asymptomatic in 10% of males and 50% of females
neisseria gonorrhoeae1

  • Males – urethritis, yellowish discharge, scarring & infertility
  • Females – vaginitis, urethritis, salpingitis (PID), common cause of sterility & ectopic tubal pregnancies
  • Extragenital infections – anal, pharygeal, conjunctivitis, septicemia, arthritis

Potential scar tissue blockage infertility


Potential for PID (pelvic inflammatory disease)

gonorrhea in newborns
Gonorrhea in newborns
  • Infected as they pass through birth canal
  • Eye inflammation, blindness
  • Prevented by prophylaxis after birth
neisseria meningitidis
  • Virulence factors – capsule, pili, IgA protease
  • Many strains exist
  • Prevalent cause of meningitis
  • Disease begins when bacteria enter bloodstream, pass into cranial circulation, multiply in meninges; very rapid onset; endotoxin causes hemorrhage and shock; can be fatal
  • Treated with penicillin, chloramphenicol
  • Vaccines exist
neisseria meningitidis1

Spread of bacteria from a nasopharyngeal infection to blood and CSF

septic shock endotoxic shock
Septic Shock-Endotoxic shock
  • LPS (lipopolysacchardide) Component of Gram negative cell wall is a potent immune stimulant.
  • May lead to circulatory failure, tissue damage and death

Release of LPS as bacteria breaks apart

aerobic gram negative bacilli
Aerobic Gram-Negative Bacilli
  • Pseudomonas – an opportunistic pathogen
  • Brucella & Francisella – zoonotic pathogens
  • Bordetella & Legionella – mainly human pathogens
  • Alcaligenes – opportunistic pathogen
  • small gram-negative rods with a single polar flagellum, produce oxidase & catalase
  • highly versatile metabolism
pseudomonas aeruginosa
Pseudomonas aeruginosa

Single polar flagellum

pseudomonas aeruginosa1
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
pseudomonas aeruginosa2
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
pseudomonas aeruginosa3
Pseudomonas aeruginosa

Skin rash/eruption

pseudomonas aeruginosa4
Pseudomonas aeruginosa

Multiple drug resistance

Staphylococcus aureus

Pseudomonas aeruginosa

  • tiny gram-negative coccobacilli
  • 2 species
    • Brucellaabortus (cattle)
    • Brucellasuis (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)
  • potential bioweapon

Undulating fever

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
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
bordetella pertussis1
  • 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

Prevalence increasing due to decrease in vaccination rate in children as a result of concern over its publicised vaccine side effects

  • live primarily in soil & water
  • may become normal flora
  • A. faecalis – most common clinical species
    • isolated from feces, sputum, & urine
    • occasionally associated with opportunistic infections – pneumonia, septicemia, & meningitis
legionella pneumophila
  • widely distributed in water
  • 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
enterobacteriaceae family
Enterobacteriaceae Family
  • enterics
  • large family of gram-negative bacteria
  • many members inhabit soil, water, & decaying matter & common occupants of large bowel of humans & animals
  • all members are small, non-sporing rods
  • facultative anaerobes, grow best in air
  • cause diarrhea through enterotoxins
  • divided into coliforms (lactose fermenters) and non-coliforms (non lactose fermenters)
diarrheal disease
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

Nosocomial Infections

Nosocomial infections from Gram negative enterics


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)

escherichia coli
Escherichia coli
  • most common aerobic & non-fastidious bacterium in gut
  • enterotoxigenicE. coli causes severe diarrhea due to heat-labile toxin & heat-stable toxin – stimulate secretion & fluid loss; also has fimbrae
  • enteroinvasiveE. coli causes inflammatory disease of the large intestine
  • enteropathogenicE. coli linked to wasting from infantile diarrhea; O157:H7 strain causes hemorrhagic syndrome & kidney damage
escherichia coli1
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
escherichia coli o157 h7
Escherichia coli O157:H7

The Ready-To-Eat Spinach outbreak of ‘06

e coli 0157 h7 outbreak
E. Coli 0157:H7 outbreak
  • September 28, 2006 : 187 people infected in 26 states (97 hospitalized…29 developed HUS)

2006 Spinach-associated outbreak




15 +

newer outbreaks
Newer Outbreaks
  • Nestle Toll House cookie dough (E. coli) June 2009) (72 cases in 30 states)
  • Ground beef (E. coli) ( July 2008) (49 cases in 7 states)
  • Pepperoni pizza (E.coli) (Oct-Nov 2007) (21 cases in 10 states)
other coliforms
Other coliforms
  • Klebsiellapneumoniae– normal inhabitant of respiratory tract, has large capsule, cause of nosocomial pneumonia, mennigitis, bacteremia, wound infections & UTIs
  • Enterobacter – UTIs, surgical wounds
  • Serratiamarcescens – produces a red pigment; causes pneumonia, burn & wound infections, septicemia & meningitis
  • Citrobacter – opportunistic UTIs & bacteremia
noncoliform lactose negative enterics
Noncoliform lactose-negative enterics
  • Proteus
  • Salmonella & Shigella
  • Swarm on surface of moist agar in a concentric pattern
  • Cause UTI, wound infections, pneumonia, septicemia, & infant diarrhea
  • S. typhi – typhoid fever – ingested bacilli adhere to small intestine, cause invasive diarrhea that leads to septicemia. Asymptomatic carriers perpetuate and spread the bacteria.
  • S. enteritidis – 1,700 serotypes (varieties)-salmonellosis – can be zoonotic(fecal contamination of food products) (1/3 of all chickens have Salmonella)
    • Food Poisoning-gastroenteritis for 2-5 days

Phases of Typhoid Fever





  • 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 & ciprofloxacin & sulfa-trimethoprim

Patches of mucus and blood

yersinia pestis
  • Nonenteric…tiny, gram-negative rod
  • virulence factors –

*capsular & envelope proteins that protect against phagocytosis & foster intracellular growth



yersinia pestis1

Yersia pestis in blood

yersinia pestis2
  • humans develop plague through contact with wild animals (sylvatic plague) or domestic or semidomestic animals (urban plague) or infected humans
  • found in 200 species of mammals – rodents without causing disease
  • flea vectors – bacteria replicates in gut, coagulase causes blood clotting that blocks the esophagus; flea becomes ravenous
yersinia pestis3

Infection cycle

pathology of plague
Pathology of plague
  • bubonic – bacillus multiplies in flea bite, enters lymph, causes necrosis & swelling called a bubo in groin or axilla
  • septicemic – progression to massive bacterial growth; virulence factors cause intravascular coagulation & subcutaneous hemorrhage. Necrosis and skin blackening occur – black plague
  • pneumonic – infection localized to lungs, highly contagious; fatal without treatment
  • treatment: streptomycin, tetracycline or chloramphenicol
  • Killed or attenuated vaccine that gives a short-term protection exists
pasteruella multocida
  • zoonotic genus
  • opportunistic infections
  • animal bites or scratches cause local abscess that can spread to joints, bones, & lymph nodes (septicemia)
  • treatment: penicillin & tetracycline
  • tiny gram-negative pleomorphic rods
  • Fastidious. can’t grow on blood agar without special techniques.
  • some species are normal colonists of upper respiratory tract or vagina (H. aegyptius, H. parainfluenzae)
  • others are virulent species responsible of conjunctivitis, childhood meningitis, & chancroid
  • H. influenzae– acute bacterial meningitis, epiglottitis, otitis media, sinusitis, pneumonia, & bronchitis
    • meningitis symptoms: fever, vomiting stiff neck neurological impairment. High fatality is untreated
    • subunit vaccine Hib
  • H. aegyptius–conjunctivitis, pink eye
  • H. ducreyi– chancroid STD
  • H. parainfluenzae & H. aphrophilus– normal oral & nasopharyngeal flora; infective endocarditis