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Lecture 1
Scanning electron micrograph of Staphylococcus aureus bound to the surface of a human neutrophil. “Granulocytic Phagocytes,” by Frank R. DeLeo and William M. Nauseef.
Learning Objectives
By the end of this lecture you should be able to:
1. Describe the general mechanisms by which hosts resist colonization by
pathogenic microbes
2. Discuss the ways in which the normal flora contributes to the balance
between health and disease.
3. Explain the concept, components and mechanisms of bacterial virulence
and pathogenicity
Describe the stages in bacterial infection.
List and discuss the major features of the seven species of bacteria most
often involved in multiple systemic infectious diseases.
Bloch KC. Ch. 4 Infectious Diseases, Pgs. 61-69 In: Hammer GD and McPhee Eds. JS.
Pathophysiology of Disease: An Introduction to Clinical Medicine, 7th Ed. New York:
McGraw-Hill Education, 2014 (On Thumb drive.)
Infection results…
…when an exogenous agent is introduced into a host from the
environment or
…when an endogenous agent overcomes innate host immunity to
cause disease
o Host susceptibility plays an important role in either of these
settings
Function of cytokines:
Tumor necrosis factor-α (TNF-α)
o Induces the inflammatory response
lnterleukin-1 (IL-1)
o Induces fever, which enhances the immune response
Interleukin-6 (IL-6)
o Induces the acute-phase response
Interleukin-8 (IL-8)
o Chemotactic factor for neutrophils
Interlukin-12 (IL-12)
o Activates NK and Th1 cells
Marc Imhotep Cray, M.D.
host-agent-environment interaction model
Fundamental relationships involved in
the host-agent-environment interaction
model
In the host, pathogenetic mechanisms
extend from level of populations
(eg, person-to-person transmission) to
level of cellular and molecular processes
(eg, genetic susceptibility)
The environment includes vectors
(insects and other carriers that transmit
infectious agents) and zoonotic hosts or
reservoirs (animals that harbor Hammer GD and McPhee. Pathophysiology of Disease: An
infectious agents and often act to Introduction to Clinical Medicine, 2014
• Defenses include:
physical barriers
mechanical processes
specializes immune cells
secretory immunity
production of noxious compounds
normal flora
Marc Imhotep Cray, M.D. 9
Physical barriers
Skin: physical barrier and other antimicrobial properties
acidic pH (5-6)
contains lactic acid, fatty acids (in sweat)
normal skin flora (compete with pathogens)
Filtration of inhaled air: turbinate bones
Tears: lysozyme target peptidoglycan structure of gram-
positive cell walls
Commensal bacteria: skin, GI tract (compete with potential
pathogens)
Acidity: stomach, vagina
Marc Imhotep Cray, M.D. 10
Mechanical processes
Flushing: flow of fluid over mucosal surfaces removes bacteria
that are not specifically attached
urine flow in urogenital tract
gut contents in GI tract acid in stomach, pancreatic enzymes, bile,
Paneth cells (secrete defensins and lysozymes),peristalsis
tears over cornea
Contribute to immunity
induce low levels of circulatory & secretory antibodies which cross react with
pathogens
Marc Imhotep Cray, M.D. 16
Normal flora - examples
Skin: Staphylococcus epidermidis, micrococci, corynebacteria
Oral: streptococci, lactobacilli, staphylococci, corynebacteria,
bacteriodes
Nasal cavity: S. epidermidis, S. aureus, corynebacteria
Urogenital: staphylococci, corynebacteria, E. coli, Lactobacillus
acidophilus
GI tract: E. coli, entercocci, bacteriodes, lactobacilli
IMPORTANT TO NOTE:
THE STUDY OF MICROBIAL VIRULENCE FACTORS IS A MAJOR EMPHASIS IN
MICROBIOLOGY AND INFECTIOUS DISEASE RESEARCH
Le T and Bhushan V. Microbiology. In: First Aid for the USMLE Step 1 2015
Marc Imhotep Cray, M.D. Le T and Bhushan V. Microbiology. In: First Aid for the USMLE Step 1 2015
Question
A 54-year-old man develops a pyogenic infection along the suture line after
knee surgery. The laboratory gives a preliminary report of a beta-hemolytic,
catalase-positive, coagulase-positive, Gram-positive coccus. The most likely
causative agent is
(A) Moraxella catarrhalis
(B) Staphylococcus aureus
(C) Staphylococcus epidermidis
(D) Streptococcus agalactiae
(E) Streptococcus pyogenes
Marc Imhotep Cray, M.D. Le T and Bhushan V. Microbiology. In: First Aid for the USMLE Step 1 2015
The World from the Microbe's Perspective
MISSION: SURVIVE AND MULTIPLY TO ENSURE
Microbes cannot think; SURVIVAL OF THE SPECIES.
they simply exploit the
human environment
solely for growth and
survival
3. Lab ID: fastidious—does not grow on blood agar (BA) but grows on
chocolate agar (chocolate agar positive) or near Staph. aureus on BA (satellite
colonies); or with X (hematin) and V (nicotinamide adenine dinucleotide
[NAD]) factor supplementation on nutrient agar
b. In ] 1980s, some MSSA strains developed a new cell wall synthetic enzyme (PBP) made by
the mecA gene, which allows bacterium to build peptidoglycan in presence of methicillin or
nafcillin these strains are known as methicillin-resistant Staph. aureus (MRSA)
c. Now, there are vancomycin-intermediate Staph. aureus (VISA) with thick cell walls that bind
high levels of vancomycin and vancomycin-resistant Staph. aureus (VRSA) with even higher
resistance similar to vancomycin resistant enterococci (VRE)
Viruses Bacteria
Size
10-100 times larger
71
Sources and further study:
Chen EM and Kasturi SS. Deja review, Microbiology and Immunology 2nd Ed. New York: McGraw-Hill,
2010
Kishiyama JL. Ch. 3 Disorders of the Immune System, Pgs. 31-59 and Bloch KC. Ch. 4 Infectious Diseases,
Pgs. 61-87 In: Hammer GD and McPhee Eds. JS. Pathophysiology of Disease : An Introduction to Clinical
Medicine, 7th Ed. New York: McGraw-Hill Education, 2014
Johnson AG et al. Bacterial Diseases. In: Microbiology and immunology. 4th Ed. Baltimore: Lippincott
Williams & Wilkins, 2010
Le T and Bhushan V. First Aid for the USMLE Step 1 2015, New York: McGraw-Hill, 2015
Milner DA. Ed. Diagnostic pathology. Infectious Diseases. Philadelphia: Elsevier, 2015
Textbooks:
Ryan KJ and Ray CG Eds. Sherris Medical Microbiology, 5th Ed. New York: McGraw-Hill, 2010
Carroll KC etal. Jawetz, Melnick, & Adelberg’s Medical Microbiology 27th Ed. New York: McGraw-Hill, 2016
Marc Imhotep Cray, M.D. 72