Pathogenic Microorganisms

1
Pathogenic Microorganisms

• LMP 400/500
• October 5, 2007

2
Which of the following are eucaryotic
microorganisms

• Bacteria
• Chlamydia
• Fungi
• Mycoplasma
• Viruses

3
Types of Microorganisms

• Bacteria
• Bacteria
• Chlamydiae
• Rickettsiae
• Mycoplasmas
• Viruses
• Fungi

4
Bacteria

• Characteristics
• Free living or parasitic
• Shape
• Gram reaction
• In vitro characteristics
• Antigenic features

5
Major features of bacteria

• Ability to grow in vitro
• Gram reaction (Positive/negative)
• Biochemical features
• environment characteristics
• Constitutive enzymes
• Fermentation oxidation
• Antigens
• Capsules
• Flagella
• Virulence factors

6
The Pathogens

• Gram positive
• Staphylococci S. aureus, CNS
• Streptococci S pyogenes, S. pneumoniae
• Bacilli Corynebacteria, Listeria, Clostridia,
  Bacillus
• Spiral organisms T. pallidum, Borrelia
• Acid fast bacteria TB, Leprosy.

7
The Pathogens

• Gram negative
• N. gonorrhoeae
• N. meningitidis
• Haemophilus
• Enteric organisms E. coli, Salmonella, Shigella,
  Klebsiella, etc.
• Brucella, Francisella, Yersinia
• Campylobacter
• Legionella
• Vibrio.

8
A Gram-positive infection

• Patient visits the GP with a rash on his left
  forearm. The doctor prescribes a topical steroid
  and sends him home. 16 hrs later, the patient
  develops fever, intense pain, and presents to the
  emergency department with a compartment-like
  syndrome. After X-rays and ultrasound, the
  patient is sent to the OR for debridement. Blood
  and tissues samples are sent to the laboratory.

9
A Gram-positive infection

• The Gram-smear shows Gram positive cocci in
  chains.
• The cultures of blood and tissue grow S.
  pyogenes.
• The patient is immediately placed on clindamycin
  and penicillin and eventually does well.

10
What causes this infection?

• S. pyogenes.
• Streptolysins (S and O)
• Hyaluronidase
• Exotoxin A
• Carbohydrate and protein antigens (M and T
  proteins)
• The organism may be engulfed so that Penicillin
  alone does not work.

11
A Gram-negative infection

• A 40 year old presents to the emergency room with
  bloody diarrhea. 30 hours earlier the patient ate
  at a local hamburger joint. He is febrile, and is
  beginning to have signs of renal failure.
  Appropriate supportive therapy is given and the
  patients symptoms gradually resolve. A stool
  sample is collected and sent to the laboratory.

12
A Gram-negative infection.

• The stool sample is plated on selective and
  enrichment media and grows E. coli
• Antigenic analysis identifies the isolate as E.
  coli 0157H7.
• Other isolates from the same area are examined by
  molecular methods (e.g. PFGE) and have identical
  patterns.
• The source of the organism is determined to be a
  shipment of hamburger patties from the same
  supplier

13
Other bacteria

• Spiral organisms
• T. pallidum - Syphilis
• B. burgdorferi Lyme disease
• Acid-fast bacteria
• Mycobacterium tuberculosis
• Mycobacterium leprae
• Nocardia/Actinomyces

14
Antimicrobial Susceptibility

• Antimicrobials act by the following mechanisms
• Inhibition of cell wall synthesis (penicillins,
  cephalosporins)
• Inhibition of cell membranes (polymyxins)
• Inhibition of protein sysnthesis
  (aminoglycosides, tetracyclines, macrolides)
• Inhibition of nucleic acids (quinolones,
  rifampin)
• Competitive inhibition (sulphonamides,
  trimethoprim)

15
What do you think is the important issue for
successful antimicrobial therapy?

• Immunocompetent host
• Susceptible organism in vitro
• Sufficient concentration at infection site
• Duration of treatment
• All of the above

16
Antimicrobial therapy

• Issues of antimicrobial therapy
• Site of infection
• Pharmacokinetics of agent
• Age of patient
• Underlying disease
• Ability of agent to reach the site and maintain
  activity

17
Antimicrobial Resistance

• Intrinsic resistance
• Some bacteria are intrinsically resistant to
  antimicrobials (e.g. E. coli to penicillins)
• Acquired resistance
• Plasmid-mediated resistance
• Constitutive resistance
• Inducible resistance

18
Chlamydiae

• Small, gram-negative, parasitic bacteria
• Taken in by selected cells
• Form inclusion bodies in the infected cells
• Cause several infectious diseases.
• Genital tract (non-gonococcal urethritis)
• Eye infections (inclusion conjunctivitis)
• Pulmonary diseases (psittacosis)
• LGV

19
Rickettsiae

• Parasites of insects
• Transmitted by insect bites
• Multiply in cells of small blood vessels
• Febrile illnesses, often associated with skin
  rash
• Examples.
• Typhus
• Rock Mounted Spotted fever.

20
Mycoplasmas

• Bacteria that lack a cell wall.
• Free living, rely on osmotic pressure differences
  so they dont rupture
• Cause a number of infections
• Primary atypical pneumonia (M. pneumoniae)
• Genital infections (M. hominis, U. urealyticum)
• Extraintestinal infections (M. hominis, etc)

21
Viruses

• Parasitic existence.
• Have DNA or RNA but not both.
• Single or double stranded nucleic acid
• Enclosed within a protein coat (capsid)
• Some viruses have a lipid envelope.
• Viruses rely on the host cell to manufacture
  viral proteins.
• The result of this interaction is either
  symbiosis with the host or overt infection.

22
Virus classification

• DNA viruses
• Adenoviruses
• Hepatitis B
• Herpes viruses HSV 1,2, EBV, VZV, Papilloma

23
Virus Classification

• RNA viruses
• Arboviruses
• Corona viruses
• Hantaviruses
• Hepatitis viruses A,B,C D, E
• Myxoviruses (Influenza, RSV, Measles, Mumps,
• Picorna Coxsackie, Echo, Polio, Hepatitis A,
  Rhinoviruses
• Rabies
• Retroviruses HIV, HTLV
• Rubella

24
Virus Diseases

• Respiratory infections (Adeno, influenza, RSV,
  EBV, Corona, Rhino, Echo, Hanta
• Liver diseases (hepatitis viruses)
• Rash diseases (Herpes, VZV, Measles, Rubella,
  Mumps)
• Encephalopathies (Herpes, Rabies, Arboviruses)

25
Viral Diseases

• Latency
• Viruses may co-exist with human cells without
  causing evidence of disease that is, no cell
  injury. Viral nucleic acid turns over at the same
  rate as host cell nucleic acid. Some viral
  particles may be released from the cells without
  evidence of disease.

26
Viral Diseases

• Active Infection.
• The result of the interaction is host cell injury
  and death (manifested as cytopathic effect)
• Latent infection may become activated from
  external forces (e.g., Herpes viruses)

27
Manifestations and therapy of viral diseases

• Host defense mechanisms
• Cytokines
• Humoral and cell-mediated immunity
• Antiviral agents
• Targets
• DNA, RNA synthesis,
• Prevention of protein coating.
• Activation of host responses (e.g., interferon)

28
Fungi

• Eucaryotic organisms that are free-living.
• Usually found in the natural environment
• Exist as molds or yeasts.
• Cause either superficial or systemic infections.

29
Fungal Infections

• Superficial infections
• Superficial infection (Pityriasis versicolor)
• Do not penetrate the dermal layers
• Dermatophytic infections
• Athletes foot, tinea, onychomycosis
• Other superfical infections
• Candidal vaginitis

30
Fungal Infections

• Deep fungal infections
• Coccidioidomycosis (C. immitis)
• Histoplasmosis (H. capsulatum)
• Blastomycosis (B. dermatitidis)
• Sporotrichochosis (S. schenckii)
• Candida infections
• Cryptococcosis

31
Deep Fungal Infections

• Criteria for infection
• Environmental geographic
• Underlying disease
• Areas where spores may be present
• Time of year.
• Use of broad spectrum antibacterial agents

32
Treatment of fungal infections

• Most antifungal agents are toxic to the host.
• Agents are either topical (e.g., griseofulvin,
  terbinifine) or
• Systemic
• Amphotericin B ergosterol synthesis
• Fluconazole Azole, membrane activity
• Echinocandins sysnthesis of glucose polymers
• Nucleic acid synthesis e.g., rifampin, if cell
  wall is opened.

33
Of the following infectious processes which are
the most difficult to treat?

• MRSA soft-tissue infections
• HIV
• Mycoplasma pneumonia
• Gonorrhoea
• Invasive candidaiasis