Transcript I always tell my students at the start of every lecture

I always tell my students at the start of every lecture:
“If a smart man can understand the entire concept in an hour, while it
will take you the whole day to do so, then better start making that
coffee.”
MICROBES & HUMANS
A n ASMPH FILM
Introducing
WITH
THE
BUGS
OUR WITS versus THEIR GENES
“The global future
of mankind will
probably unfold
as episodes of a
suspense thriller
that could be entitled
Our Wits Versus Their Genes.”
Joshua Ledeerberg
Raul V. Destura MD
Consultant-Director
Section of Molecular Diagnostics and Section of Clinical Microbiology
The Medical City
 Is a branch of science that relates to interactions
between man and microorganisms.
 In practice, the science deals mainly with the ill health
resulting from such interactions – infections or
infectious diseases
 The term is usually applied to any condition that:
 is easily transmitted between individuals
 is caused by an identifiable microorganism
 may, following initial infection, confer protection
(immunity) from subsequent
 infection with the same microorganism.
The Affected Host
2. An Infectious Agent
3. The Environment
1.
 Infectious diseases in man are caused by
microorganisms (living organisms of microscopic
size) from the following
 five groups:
 bacteria
 viruses
 Fungi
 protozoa
 helminths.
 Contain the largest number of species that are
pathogenic to human
 Single-celled and contain both DNA and RNA and
produces by binary fission
 A few lack all the machinery necessary for
replication and must interact with host cells to
reproduce (Ricketsiaceae, Anaplasmataceae,
Chlamydiaceae)
 Single and multicelled agents that are further
differentiated into a defined nucleus and
cytoplasm
 Yeast- single celled fungi that reproduce by
binary fission
 Molds or Moulds – more complex multicelled
organisms that reproduce by both sexual and
asexual means
 Some are Dimorphic
 Large and very complex group of microbes
 Include single celled animals –protozoa
 Others are very complex, multi-celled organisms that
have well defined organs and tissues, such as GI and
genital systems
 Do not have complete genetic machinery for their own

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propagation
Either a DNA or RNA
Must infect other life form to survive
Represent the simplest form of infectious Agents
Reproduce by replication of their nucleic acid
 Bacteria have been classified on the basis of their
staining properties for about 120 years.
 The method differentiates between two major
groups of bacteria with very different cell envelopes.
 Gram-positive bacteria retain the stain (crystal
violet) and appear blue, whereas gram-negative
bacteria usually appear pink due to the counterstain
safranin.
Fig. 7-37b, p.232
Commercial break……..
Developed by:
Hans Christian Gram, 1884
Differential stain
Discriminates between different
cell types – Gram positive and Gram
negative
 Gram positive
 Dark purple
 Gram negative
 Pink
Cocci in clusters: e.g. Staphylococci
Cocci in chains: e.g., Streptococci
Cocci in tetrads: e.g., Micrococci
Bacilli or Rods
Cocci in pairs (or Diplococci)
Bacilli or Rods
Issues
• selective pressure
• antimicrobial resistance
• plasmid mediated
• chromosomally mediated
• Plasmids
• Extra-chromosomal DNA
• multiple copy number
• coding pathogenesis and antibiotic
resistance factors
• bacterial replication
•
•
•
•
Some bacteria are motile
Locomotory organelles- flagella
Taste environment
Respond to food/poison
– chemotaxis
• Flagella
– embedded in cell
membrane
– project as strand
– Flagellin (protein)
subunits
– move cell by
propeller like
action
 spirochetes
 similar function to flagella
 run lengthwise along cell
 snake-like movement
Making Wall-less forms
•
Result from action of:
– enzymes lytic for cell wall
– antibiotics inhibiting peptidoglycan biosynthesis
•
Usually non-viable
•
Wall-less bacteria that don’t replicate:
– spheroplasts (with outer membrane)
– protoplasts (no outer membrane).
•
Wall-less bacteria that replicate
– L forms
 Mycloplasma
Capsules and slime layers
•
•
•
•
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outside cell envelope
well defined: capsule
not defined: slime layer or glycocalyx
usually polysaccharide
often lost on in vitro culture
protective in vivo
•
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Dormant cell
Produced when starved
Resistant to adverse conditions
- high temperatures
- organic solvents
contain calcium dipicolinate
Bacillus and Clostridium
 Portals of Entry
 Respiratory
 Gastrointestinal
 Genitourinary tracts
 Accidental Areas: mucus membranes and skin
(A) Portals of entry. (B) Portals of exit.
Source of Agent
Mechanism for Entry
Portal of Entry
Example
Infected Human
Aerosol
Respiratory
Influenza Virus
Infected Human
Direct Contact
Cutaneous
Herpes Simplex in wrestlers
Infected Human
Sexual Intercourse
Genital
Syphilis; gonorrhea
Infected Human
Oral or nasopharyngeal
secretions to eye
Ocular
Bacterial or viral conjunctivitis
Contaminated Environment
Transfusion of Blood products
Intravascular
Hepatitis virus
Contaminated Environment
Food or water
Gastroentestinal
Enteric bacterial and viral
pathogens
Infected Animal
Cooling tower drift
Respiratory
Legionaires Disease
Infected Tick
Animal bite
Cutaneous
Rabies
Patient
Tick bite
Cutaneous
Lyme Disease
Patient
Aspiration of endogenous flora
Respiratory
Bacterial Pneumonia
Patient
Spillage of intestinal flora
through a damaged wall
Gastroentestinal
Bacterial Peritonitis
Patient
Migration of Bacteria from
oropharynx to middle ear
through Eustachian tube
Ear
Bacterial otitis media
 LD50 and ID50
 Some characteristics that give infectious agents a leg
up in the battle with their chosen hosts
 Involves invasiveness and toxigenicity
 Not an all or none phenomenon
 Adherence
 Initial requirement for organisms to invade hosts
 The process by which bacteria stick to the surface of
host cells
 A.k.a. Adhesion and Attachment
 Adherence is dictated by several factors
 Surface hydrophobicity and net surface charge
 Binding molecules on bacteria (ligands)
 Host cel receptor interaction
 Surface hydrophobicity
 The more hydrophobic the bacterial cell surface, the
greater the adherence to the host cell
 Different strains of bacteria differ in hydrophobicity
thus some are more virulent than others
 Pili (fimbriae)
• hair-like projections of the cell
• sexual conjugation
• adhesion to host epithelium
 Tissue-Degrading Enzymes
 Collagenase (C. perfringens)
 Coagulase (S. aureus)
 Hyaluronidase (Staph and Strep)
 Streptokinase (Strep)
 Hemolysins and Leucocidine
 IgA1 Proteases
 Allows pathogens to inactivate the primary antibody found
on mucosal surfaces and thereby eliminate protection of the
host by the antibody
 Exotoxins and Endotoxins
 Properties
 Mechanisms
Exotoxins
Endotoxins
Excreted by living cells
Integral part of cell walls of G- bacteria
Produced by both G+ and G- bacteria
Found only in G- bacteria
Polypeptide; MW 10,000-900,000
LPS complexes (Lipid A)
Heat labile
Heat Stable
Highly antigenic
Weakly Immunogenic
Can be converted to toxoids
Cannot be used as toxoids
Highly toxic even at small doses
Moderately toxic
Has specific binding receptors
No specific receptors
Usually do not produce fever
Induces release of IL-1 and other
mediators
Plasmid mediated control
Chromosomally mediated
Exotoxins
Endotoxins
Diptheria
Physiologic Effects
Tetanus
Fever
Botulism
Leucopenia
Gas Gangrene
Hypotension
Streptococcal Erythrogenic Toxins
Impaired Organ Dysfunction
TSST-1
C3 and complement cascade
activation
Exotoxins associated with diarrheal
disease and food poisoning
DIC
That’s why we need to make sure
we clearly understand what we
read!