Transcript Pathogenesis of Bacterial Infections: Host, Parasite, Environmental

Introduction to the Microbial World 1
Professor A G Duse
Chief Specialist and Head (Chair): CMID
NHLS and Wits School of Pathology
Room 3T11, Level 3, WMS
Tel #: 489 8510
Lecture Objectives:
1.
2.
3.
4.
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6.
Briefly describe the evolutionary relationships of living
organisms
List the main distinguishing features of prokaryotic versus
eukaryotic cells
Provide a simple classification of the different forms of
microbial life
Understanding the underlying principles of microbial
taxonomy
Understand the concept of microbial morphology and its
importance in clinical microbiology
Draw an annotated diagram of a typical bacterial cell
Molecular Phylogeny:
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Cyanobacteria (~3.6 billion years old) earliest evidence of unicellular life
Molecular phylogeny: tool that enables us to understand the complexity of
life & recognize the relationships of living forms
Determined by comparing difference in homologous genes encoding
ribosomal RNA (16S r RNA genes from PROKARYOTIC cells & 18S rRNA
from eukaryotic cells)
Computer analysis of rRNA gene sequences => life has evolved along 3
major lineages:
1.
2.
3.
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Bacteria &
Archae – not clinically significant (solely microbial & composed of only unicellular
organisms), and
Eukaryotes (more complex, multi-cellular organisms)
Hence, prokaryotes & eukaryotes; both ancient & derived from a common
UNIVERSAL ancestor!
Homo sapiens & other species either live in harmony (colonization) or are
diseased (infected with manifest symptoms and signs to cause
PATHOLOGY) with both prokaryotic and eukaryotic organisms!
Differences Between Prokaryotic
and Eukaryotic Cells:
PROKARYOTES
 nucleoid
 no nuclear membrane
 haploid chromosome
 no mitotic division (replicate by
binary fission)
 no mitochondria
 no Golgi apparatus,
microtubules
 70S ribosomes
 motile by flagella
EUKARYOTES
 nucleus
 present
 diploid
 mitotic division
 present
 present
 80S ribosomes
 more complex
Classification of Microbes:
Micobial World
Viruses
DNA
or
RNA
Bacteria
Fungi
Parasites
Cocci
Yeasts
Bacilli
Dimorphic
Spiral
Moulds
Protozoa
Trematodes
Cestodes
Nematodes
Nomenclature (Taxonomy) of Bacteria:
 FAMILY:
The Enterobacteriaceae
 GENUS:
Salmonella
Escherichia
Binomial classification:
Genus and species
 SPECIES:
typhi
coli
(S typhi OR S typhi)
(E coli OR E coli)
Bacterial Morphology:
SIZE: microns
SHAPE:
ARRANGEMENT
e.g. cocci in chains
e.g. cocci in clusters
ULTRASTRUCTURAL FEATURES: capsules, flagella,
fimbriae / pili; spores
Bacterial Cell Structure:
Introduction to the Microbial World 2
Professor A G Duse
Chief Specialist and Head (Chair): CMID
NHLS and Wits School of Pathology
Room 3T11, Level 3, WMS
Tel #: 489 8510
Lecture Objectives:
•
•
•
Using a bacterial cell as an example, describe the ultrastructural features of bacteria & discuss both their
laboratory & clinical relevance
Discuss the role of bacterial cell components in disease
causation (pathogenesis)
Classify bacteria according to their morphology, aerotolerance, and staining reactions with particular emphasis
on Gram and acid-fast stains
Bacterial Cell Components:
Bacterial Cell Components:
 Capsule (mostly polysaccharide): antiphagocytic; antigenic/
immunogenic
 Flagella (proteinaceous): locomotion; antigenic; ? Immune evasion
 Fimbriae/pili: adherence
 Cell wall (cytoskeleton = peptidoglycan): rigidity & shape;
protection against osmotic pressure - prevention of lysis; antigenic
 Cytoplasmic membrane: cell respiration; cell precursor synthesis
 Intracytoplasmic inclusions; DNA; ribosomes
 Spores: protect species of genera Bacillus and Clostridium from
unfavourable conditions
Construction of the Cell Walls of Gram-positive and
Gram-negative Bacteria:
LIPOPOLYSACCHARIDE
(ENDOTOXIN)
Bacterial Morphology:
STAINING REACTIONS:
Gram staining:
Gram-positive (dark-blue/purple)
Gram-negative (pink)
Acid-fast:
• stains poorly with Gram stain e.g. Mycobacterium
tuberculosis
• Ziehl-Neelsen stain; Kinyoun stain; auramine stain
Morphology-based bacterial classification:
Man versus Microbes:
Professor A G Duse
Chief Specialist and Head (Chair): CMID
NHLS and Wits School of Pathology
Room 3T11, Level 3, WMS
Tel #: 489 8510
Objectives:
• Understand the concept of infectious disease causation
• Discuss the interactions between hosts, microbes and the
environment
• Describe the concepts of true virulence versus opportunism
• List, and using appropriate examples, discuss the 7 major
challenges that a microbe must overcome to cause infection
• Illustrate all of the above by briefly discussing the recent
outbreak caused by Rift Valley Fever virus in Kenya (Dec
2006-Jan 2007)
Definitions:
X-REF IMMUNOLOGY: INNATE/NONSPECIFIC DEFENCE MECHANISMS
HOST
• Pathogenesis
FOCUS OF TODAY’S
LECTURE
MICROBE
ENVIRONMENT
• Pathogens: “true”/”primary” vs. “opportunistic” vs. “colonizers”
• Carrier state
• Virulence: ID 50, LD 50; other
Pathogenic Bacteria:
The Seven Challenges
• Maintain a reservoir
– Human, animal, environmental
• Gain access to a new host
– Portal of entry; mode of transmission
• Adherence: non-specific & specific mechanisms
• Establishing infection: evading host defences (X-ref: Immunology)
• Mechanisms of disease causation
– Adherence; toxins (exotoxins, endotoxin); hypersensitivity/autoimmune reactions
(X-ref: Immunology)
• Exiting from one host, entering another
Portals Of Entry:
• Respiratory tract
• Gastrointestinal tract
• Genitourinary tract
• Skin and mucous membranes
Modes Of Transmission:
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By respiratory droplets; droplet nuclei
Airborne (other than above)
Faecal-oral
By direct body contact
By fomites
Parenteral
By arthropod vectors
Remember:
• Adherence; + / • Invasion; +/ • Toxin production
– Differences between exotoxins & endotoxins; + / -
• Hypersensitivity reactions
Pathogenic Bacteria:
The Seven Challenges
• Maintain a reservoir
– Human, animal, environmental
• Gain access to a new host
– Portal of entry; mode of transmission
• Adherence: non-specific & specific mechanisms
• Establishing infection: evading host defences (X-ref: Immunology)
• Mechanisms of disease causation
– Adherence; toxins (exotoxins, endotoxin); hypersensitivity/autoimmune reactions
(X-ref: Immunology)
• Exiting from one host, entering another
Rift Valley Fever:
RVF Kenya Dec 06 - Jan 06:
Natural cycle of RVFV:
Infected flood water Aedes & Culex sp. oviposit
Eggs with virus dormant
Heavy rains flood
Infectious mosquitoes hatch
Mosquitoes feed on livestock and occasionally humans
Amplification in vertebrate host
Ocular RVFV:
‘Macular scarring’
Al-Hazmi et al., CID 2003; 36:24
Hemorrhagic RVF:
Epizootic cycle of RVFV:
Livestock (mainly sheep, cattle, goat) infected by vector
Incubation followed by viremia and illness
Feeding by uninfected vectors
Extrinsic incubation
Newly infectious vector
Slaughter, abortion, or necropsy
Aerosol or contact infection
of humans
RVFV – a worldwide concern
• Many mosquitoes world-wide can be vectors in the lab and in
the field at blood meal virus concentrations found in sheep,
cattle, humans
• We know it can cause epidemics when vertebrates that
develop high viremias are present (sheep, cattle, goat)
• Mortality in domestic livestock and subsequent trade
interruption have severe economic impact
• Humans may visit endemic/epidemic areas and return to their
homes within an incubation period (e.g., tourist with
retinopathy)
• Both arthropod and direct transmission from blood efficient
(concern: bioterrorism and aerosols)
• Established epidemics in new territory: Egypt, Saudi, Yemen
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