Presented By : Rody's group

General Principles of
Microbial Pathogenesis
Categories of Infectious Agents
The Microbiome
 GENERAL PRINCIPLES OF MICROBIAL
PATHOGENESIS
Humans are prey to thousands of infectious agents ranging from submicroscopic viruses to
several meters long tape worms.This chapter reviews the general principles of the
pathogenesis of infectious disease and describes the char- acteristic histopathologic changes
caused by different types of microbes.
infectious diseases are an important health problem in the United States and worldwide
despite the availability of effective vaccines and antibiotics for many types of infec- tions.
Influenza and pneumonia combined are the eighth leading cause of death in the United
States. In low-income countries, limited access to healthcare, unsanitary living conditions,
and malnutrition contribute to a massive burden of infectious diseases. Lower-respiratory
infections, HIV/AIDS, and diarrheal diseases are the top three causes of death in
developing countries, and malaria and tubercu- losis are among the top ten. Infectious
diseases are particu- larly important causes of death among children, older adults,
individuals with chronic debilitating diseases and inherited or acquired immunodeficiency
states (e.g., AIDS), and in patients receiving immunosuppressive drugs.
 Categories of Infectious Agents
Infectious agents belong to a wide range of classes and vary greatly in size, ranging from prion protein
aggregates of under 20 mm to tapeworms 10 meters in length.

PRIONS
Also known as Transmissible Spongiform Encephalopathies
Prions are composed of abnormal forms of a host protein termed prion protein (PrP). These agents
cause transmis- sible spongiform encephalopathies, including kuru (associ- ated with human
cannibalism), hereditary or sporadic Creutzfeldt-Jakob disease (CJD), bovine spongiform
encephalopathy (BSE) (better known as mad cow disease), and variant Creutzfeldt-Jakob disease
(vCJD) (probably transmitted to humans through consumption of meat from BSE-infected cattle). PrP
is found normally in neurons. Dis- eases occur when the PrP undergoes a conformational change that
confers resistance to proteases. The protease- resistant PrP promotes conversion of the normal
protease- sensitive PrP to the abnormal form, explaining the transmissable nature of these diseases.
CJD can be trans- mitted from person to person iatrogenically, by surgery, organ transplantation, or
blood transfusion.
 VIRUSES
Viruses are obligate intracellular parasites that depend on the host cell's metabolic machinery for their
replication. They consist of a nucleic acid genome surrounded by a protein coat (called a capsid) that is
sometimes encased in a lipid membrane. Viruses are classified by their nucleic acid genome (DNA or
RNA, but not both), the shape of the capsid (icosahedral or helical), the presence or absence of a lipid
envelope, their mode of replication, their preferred dell type for replication (called tropism), or the
type of pathology they cause. Some viral components and particles aggregate within infected cells and
form characteristic inclusion bodies, which may be seen with the light microscope and are useful for
diagnosis.
Other viruses are not eliminated from the body and persist within cells of the host for years, either
continuing to multiply (e.g., chronic infection with hepatitis B virus [HBV]) or survive in some latent
nonreplicating form, with the potential to be reactivated later. For example, herpes zoster virus, the
cause of chickenpox, can enter dorsal root ganglia and establish latency at the site, with periodic reac-
tivation at later times to cause shingles, a painful skin condition. Some viruses are involved in
transformation of a host cell into a benign or malignant tumor (e.g., human papillomavirus [HPV]-
induced benign warts and cervical carcinoma)

 BACTERIA

Bacteria are prokaryotes, meaning that they have a cell membrane but
lack membrane bound nuclei and other membrane-enclosed organelles
Most bacteria are
bounded by a cell wall consisting of peptideglygan, a polymer of long
sugar chains linked by peptide bridges, surrounding the cell membrane.

 There are two common forms of cell wall structure:

a thick wall that retains crystal-violet stain (gram-positive bacteria

a thin cell wali surrounded by an outer membrane (gram-negative back-ria)
Bacteria are classified by Gram staining (pos.-tive or negative), shape (spherical,
called coçei, or rod-shaped, called bacilli) , and their requirement for oxygen
(aerobic or anaerobic).

Motile bacteria have las gella, long helical filaments extending from the cell
surface that rotate and move the bacteria. Some bacteria possess pili, another
kind of surface projection that can attach bacteria to host cells or extracellular
matrix. Bacteria synthesize their own
DNA, RNA, and proteins, but they depend on the host for favorable growth
conditions. Many bacteria remain extracellular when they grow in the host, while

others can survive and replicate both outside and inside of host
cells (facultative intracellular bacteria such as mycobac-teria), and
some grow only inside host cells (obligate intra-cellular bacteria,
such as rickettsia).
 Microbial

Fungi
Fungi are eukaryotes with thick cell walls composed of
complex carbohydrates such as beta-glucans, chitin, and
Fungi mannosylated glycoproteins
Fungi can grow either as rounded yeast cells or as slender,
filamentous hyphae
Fungi may produce sexual spores or, more commonly,
asexual spores called conidia

An important distinguishing characteristic is whether hyphae are

septate (with cell walls separating individual cells) or aseptate
 Microbial

Fungi may cause superficial or deep

infections:
Superficial infection - involve the skin, hair, and nails. Fungal
Fungi
species that cause superficial infections are called
dermatophytes. Infection of the skin is called tinea; thus, tinea
pedis is “athlete’s foot” and tinea capitis is scalp ringworm.
Certain fungi invade the subcutaneous tissue, causing abscesses or
granulomas
Chronic infections, often in the foot, are called mycetomas.
 Microbial

Fungi may cause superficial or deep

infections:

Deep fungal infections - can spread systemically and

Fungi
invade tissues, destroying vital organs in
immunocompromised hosts, but usually resolve or
remain latent in otherwise normal hosts.
Microbial
Fungi are divided into:
Endemic fungi Opportunistic fungi
(e.g., Candida, Aspergillus, Mucor, Cryptococcus)

are invasive species that are by contrast, are ubiquitous organisms that either
Fungi usually limited to particular colonize individuals or are encountered from
environmental sources but do not cause severe
geographic regions (e.g., disease in healthy individuals
Coccidioides in the In immunodeficient individuals, opportunistic
fungi give rise to lifethreatening invasive
southwestern United States,
infections characterized by vascular occlusion,
Histoplasma in the Ohio hemorrhage, and tissue necrosis, with little or no
River Valley). inflammatory response
Patients with AIDS are very susceptible to infection
with the opportunistic fungus Pneumocystis jiroveci
(previously called Pneumocystis carinii)
 Microbial

Protozoa
Protozoa are single-celled eukaryotes that are major causes of disease
and death in developing countries
Protozoa can replicate intracellularly within a variety of cells (e.g.,
Protozoa Plasmodium in red cells, Leishmania in macrophages) or extracellularly
in the urogenital system, intestine, or blood
Trichomonas vaginalis organisms are sexually transmitted
flagellated protozoal parasites that often colonize the vagina and
male urethra.

 Microbial

The most prevalent pathogenic intestinal

protozoans are:

Entamoeba histolytic
Giardia lamblia

Protozoa
These two are are ingested as nonmotile cysts in contaminated
food or water and become motile trophozoites that attach to
intestinal epithelial cells
 Microbial

Bloodborne protozoa like Plasmodium, Trypanosoma,

Leishmania are transmitted by insect vectors, in which they
replicate before being passed to new human hosts.

Protozoa Toxoplasma gondii - is acquired either through contact with

oocyst-shedding cats or by eating cyst-ridden, undercooked
meat.
 Helminths
Parasitic worms are highly differentiated multicellular organisms.
Helminths comprise three groups:
Roundworms (nematodes) are circular in cross-section and non-segmented. Intestinal nematodes include A.
lumbricoides, Strongyloides stercoralis, and hookworms.Nematodes that invade tissues include the filariae, such
as Wuchereria bancrofti and Trichinella spiralis.
Tapeworms (cestodes) have a head (scolex) and a ribbon of multiple flat segments (proglottids). They adsorb
nutrition through their tegument and do not have a digestive tract.The larvae that develop after ingestion of eggs
of certain tapeworms can cause cystic disease within tissues (Echinococcus granulosus larvae cause hydatid
cysts:pork tapeworm larvae produce cysts called cysticerci in many organs)
Flukes (trematodes) are leaf-shaped flatworms with prominent suckers that are used to attach to the host. They
include liver and lung flukes and schistosomes.

Helminths
 Ectoparasites

(e.g., lice, bedbugs, fleas) or arachnids (e.g, mites, ticks, spiders) that cause disease by
Ectoparasites are insects
biting or by attaching to and living on or in the skin.

Infestation of the skin by arthropods is characterized by itching and excoriations, such as pediculosis caused by lice
attached to hairs, or scabies caused by mites burrowing into the stratum corneum.

Ectoparasites
 THE MICROBIOME
The microbiome is the diverse microbial population of bacteria,
fungi, and viruses found in or on the human body

Examples:
In the intestinal tract
Skin
Upper airway
Vagina
Microbiome
 Microbiome's important roles in normal
health and development.
In the intestinal tract, the normal flora are responsible for
absorption of digested foods, for maintaining the integrity
of the epithelium and the normal functioning of the
intestinal immune system, and for competitively inhibiting
invasion and colonization by potentially pathogenic
microbes.
The gut microbiome is also emerging as a regulator of
Microbiome nutritional status.
 New techniques of bacterial identification relying on ribosomal
RNA sequencing have dramatically improved our understanding of
the microbiome:
• In healthy individuals, the microbiome is very diverse. In a healthy
person, a part of the bacterial population at various body sites is
relatively stable over time, but may be altered by diet and
environment.
• The diversity of bacteria is greatest in the oral cavity and the stool,
intermediate on the skin, and least in the vagina.
• The bacterial microbiomes at various body sites are partially
Microbiome similar in different individuals.
 Dysbiosis refers to changes in composition of the
microbiome that are associated with disease.

These changes may result from therapies or various

pathophysiologic conditions, including the following:

• Use of some antibiotics is an important risk factor for intestinal

infections caused by toxin producing Clostridium difficile.
• The microbiome in the stool of obese individuals is less diverse
than that of lean individuals, and the proportions of bacterial phyla
Microbiome differ as well.
 • The intestinal bacterial populations in individuals with
inflammatory bowel disease are altered, with reduced diversity
and changes in the proportions of bacterial phyla, compared to
individuals without inflammatory bowel disease.

Microbiome
Thank You
By : Rody's Group