CHAPTER 4AN INTRODUCTION TO CELL STRUCTURE AND HOST-

PATHOGEN RELATIONSHIPS

© National Institutes of Health, United States Department of Health and Human Service.

WHY IS THIS IMPORTANT?

• An understanding of cell structure is vital to understanding microbiology, in particular, the process of infection.

• Host-pathogen interactions must be understood in order to understand the processes of infection and disease.

OVERVIEW

CLASSIFICATION OF ORGANISMS

• All living organisms can be classified as

Prokaryotes Eukaryotes

No Organelles

(Bacteria)

Organelles

(Everything else)

Biological Kingdoms

Taxonomy: A system for classifying biological organisms

Genus and species

Used to identify anorganism

CLASSIFICATION OF ORGANISMS

• Biologists classify microorganisms by their genus and species names.– An example is Clostridium tetani. Clostridium is the genus

and tetani is the species.• The genus can have several species.

– E.g. Clostridium perfringens, Clostridium botulinum and Clostridium difficile, etc.

• The genus and species names of microorganisms are italicized when written.

• First letter of genus is capitalized• The genus can be abbreviated to first letter:Escherichia coli E. coli

The genus can be abbreviated to first letter:Escherichia coli E. coli

All E’s are NOT Created Equal

Enterobacter aerogenes E. aerogenesEnterococcus faecalis E. faecalis

Staphylococcus aureus S. aureusStreptococcus pneumoniae S. pneumoniae

BACTERIA: Overview

• Microscopic

• Immensely diverse

• Successfully colonize all parts of the world and its inhabitants.

• Considered Pathogens if they cause disease.

BACTERIA: Size, Shape and Multicellular Arrangement

• Bacteria can be of different shapes, sizes, and arrangements.

• The most common shapes:– Coccus (circular)– Bacillus (rod)– Spirilla (spiral)

Multicellular Arrangements

Chain

Clusters, clumps

Many organisms have no arrangement.

BACTERIAL STAINING: Types of Stain

• Bacteria can be stained in the following ways:– Positive stains – stain the organism– Negative stains – stain the background– Simple stains – stain using only one color– Differential stains – stain using more than one

color

THE GRAM STAIN

• Differentiates bacteria based on differences in the structure of their cell walls.

• The Gram stain process divides bacteria into four major groups:– Gram-positive– Gram-negative– Gram-variable– Gram nonreactive Gram neg. bacilli Gram pos. cocci

THE GRAM STAIN

THE NEGATIVE (CAPSULE) STAIN• Stains the background surrounding encapsulated bacteria.

• Capsules serve as important virulence factors for some organisms:

• Streptococcus pneumoniae (pneumonia, meningitis, etc.)• Hemophilus influenzae (pneumonia, meningitis, etc.)• Neisseria meningitidis (bacterial meningitis)• Bacillus anthracis (anthrax)

THE FLAGELLA STAIN

• The flagella stain identifies the presence of flagella, which are used for motility.

• Motility is important for infection as it allows the invading organisms to move from the initial site of infection.

THE ZIEHL-NEELSEN ACID FAST STAIN

• Used to detect Mycobacterium species such as M. tuberculosis (the cause of tuberculosis) or M. leprae (the cause of leprosy).

• These organisms have mycolic acid in their cell walls, making the cell wall difficult to penetrate.

THE ENDOSPORE STAIN• Endospores are small, tough, dormant structures that

can form in certain bacteria.

Crystal Violet StainExcluded from spores

Malachite Green Spore Stain

HOST-PATHOGEN RELATIONSHIPS• Infectious diseases are complex and involve the

ongoing interaction between the host and the pathogen.– HOST PATHOGEN

• Many factors affect this relationship.

HOST-PATHOGEN RELATIONSHIPS

• Infectious diseases are complex and involve a series of shifting interactions between host and pathogen.

• For the pathogen, the interactions depend on:

– Ability to evade or overcome the host’s defense– Ability to increase in numbers– Ability to transmit to new hosts.

Covered in greater detail next week.

HOST-PATHOGEN RELATIONSHIPS

• For the host, the interactions depend on:

– The host having useful functioning defenses– The host’s susceptibility to infection

Covered in greater detail in weeks 6 and 7.

PATHOGENICITY: All Microbes Are Not Created Equal

Commensals, Opportunists and Pathogens

Commensals – Do not harm the host

Mutualists – Benefit the host while deriving benefit from the host

Opportunists – Can become pathogens given the proper conditions (injury, immune compromised, etc.)

Pathogens – Overtly cause disease

• Microbial flora can protect us through microbial antagonism.– Many bacteria produce bacteriocins which are

localized bacterial antibiotics. – Bacteriocins can kill invading organisms but do

not affect the bacteria that produce them.

Competition for space and other resources.

HOST-PATHOGEN RELATIONSHIPS

• In most cases, the interactions between the body and bacteria cause no harm.– Some bacteria have a mutualistic relationship with the

host.• However, some harmless organisms can become

opportunistically pathogenic.

OPPORTUNISTIC PATHOGENS AND PRIMARY PATHOGENS

• Opportunistic pathogens cause infection by taking advantage of a hosts’ increased susceptibility of infection.

• Characteristics of primary pathogens are as follows:– They cause disease in healthy individuals.– They include viruses and bacteria.

OPPORTUNISTIC PATHOGENS AND PRIMARY PATHOGENS

• Characteristics of primary pathogens are as follows:– They have evolved mechanisms that can overcome

host defenses.– Once inside, they can multiply rapidly.

– Some primary pathogens are restricted to humans.– Some pathogens can infect humans and other

animals (zoonosis)

DISEASE AND TRANSMISSIBILITY

• Successful infection requires the following from a pathogen:– The ability to multiply in sufficient numbers– The ability to transmit to new hosts.

DISEASE AND TRANSMISSIBILITY

• Symptoms of certain infections can provide transmission mechanisms through:– Coughing transmits respiratory infections.– Diarrhea transmits digestive infections.

• Infections that kill too quickly inhibit transmission.

BACTERIAL PATHOGENICITY AND VIRULENCE

• Pathogens must be able to accomplish the five requirements for infection:– Entry (getting in)– Establishment (staying in)– Defeat the host defenses – Damage the host– Be transmissible

•Entry•Colonization•Immune Evasion•Propagation•Transmission

PATHOGENICITY AND VIRULENCE

• Virulence refers to how harmful a pathogen is to the host.– Virulence depends on genetic factors of the pathogen.– These genetic elements are often turned on only in the

host.

BACTERIAL PATHOGENICITY AND VIRULENCE

• Pathogens carry virulence genes in clusters called pathogenicity islands.– These can be located on plasmids.– Plasmids can be transferred between cells.

QUORUM SENSING• Organisms sense their environment using special

sensing proteins. This is called quorum sensing.

• This sensing is based on population densities.

• Certain genes are only turned on when there are enough cells present:

An example of this is enterotoxin production in Salmonella.

BIOFILMS• Bacteria can grow in aggregated assemblies called biofilms.• Biofilms are clinically important because:

– They can capture and retain nutrients (allowing continued growth).

– They impede uptake of antibiotics and disinfectants.– They inhibit phagocytosis.

BIOFILMS

• Biofilms can build up on medical devices such as:– Catheters– Heart valves– Prosthetic devices

• Biofilms are one of the causes of plaque build-up on teeth.

Lead to nosocomial(hospital acquired) infections

THE HOST CELL

• There are several differences between prokaryotic and eukaryotic cells.

• Animals, including humans, possess eukaryotic cells.

• Many of the structures of eukaryotic cells play a role in infection.

EUKARYOTIC CELLS:

Bacterial anatomy will be covered in week 3 (chapter 9).

EUKARYOTIC CELLS: The Plasma Membrane

• The eukaryotic plasma membrane is made up of a phospholipid bilayer.

• It is a fluid matrix containing a variety of proteins and other molecules.

EUKARYOTIC CELLS: Role of the Plasma Membrane in Infection

• Because the plasma membrane is the barrier between the inside and the outside of the cell, it must be breached if pathogens are to gain entrance.

EUKARYOTIC CELLS: Cytoplasm• The eukaryotic cytoplasm consists of:

– A semi-fluid material that is mainly water and dissolved substances

– Membrane-bound structures called organelles– Structures not bound by membranes.

EUKARYOTIC CELLS: Role of the Cytoplasm in Infection

• Cytoplasm is involved in a variety of infections.

• It has a major role in viral infections.

• Many viruses replicate in the host cell cytoplasm.

EUKARYOTIC CELLS: Host Cell Cytoskeleton

• The cytoskeleton gives eukaryotic cells structural integrity.

• The cytoskeleton is involved in how cells are joined together to form tissue.

• The components of the cytoskeleton play a role in cellular mitosis and meiosis.

Role of the Cytoskeleton in Infection• Many pathogens use the

cytoskeleton as part of the infection process.

• Shigella use microfilaments to move laterally between cells of the intestine.

EUKARYOTIC CELLS: Cilia

• Cilia are made up of microtubules that can be projected outward from the cell surface.

• The lower respiratory tract which is lined with ciliated cells that work together with mucus-producing cells to move trapped particles upward and out of the respiratory tract.

• Muco-cilliary elevator

EUKARYOTIC CELLS: Role of Cilia in Infection

• Pathogens can attack the cilia and destroy their trapping capability.

• In some respiratory diseases, such as pertussis (whooping cough), the pathogens (in this case Bordetella pertussis) attach to host ciliated cells as an initial part of the infection.

EUKARYOTIC CELLS: Ribosomes

• Ribosomes are the site of protein synthesis.

• They are found either individually or attached to the endoplasmic reticulum.

• Ribosomes in eukaryotic cells have a different structure to those prokaryotic cells.– Difference used to develop antibiotics

EUKARYOTIC CELLS: Role of the Ribosome in Infection

• Eukaryotic ribosomes are very important in viral infections.– The virus takes over the host cell ribosome

function.– It is then used only to make new virus.

ER & Golgi Apparatus• Both systems of membranes that form flattened sacs.• The endoplasmic reticulum (ER) can be smooth (without

ribosomes) for lipid synthesis, or rough (with attached ribosomes) for protein synthesis.

ER & Golgi Apparatus • The Golgi apparatus has the three following functions:

– Modifying and packaging products coming from the ER– Renewing the cell’s plasma membrane– Producing lysosomes

The ER & Golgi Apparatus in Infection• Both structures are involved in the biosynthesis and

assembly of viruses.

• The ER is also involved in the adaptive immune response to infection.

Lysosomes• Lysosomes are filled with destructive enzymes and

chemicals.• They destroy foreign materials that enter the cell.• They also act in recycling host cell components.

Role of the Lysosome in Infection

• Lysosomes fuse with phagocytic vesicles and destroy invading pathogens.

• Many pathogens can defeat this defense.

EUKARYOTIC CELLS:The Nucleus

• The nucleus is the location of the cellular DNA of eukaryotic cells.

• The nucleus is bound by a double phospholipid bilayer membrane.

• It is the site for DNA replication during cell division.

• The transcription of messenger RNA also occurs here.

EUKARYOTIC CELLS: Role of the Nucleus in Infection

• The nucleus of the host cell is important in many infections, particularly those caused by DNA viruses.– Copies of the viral DNA are made in the nucleus.

EUKARYOTIC CELLS: Endocytosis & Exocytosis

• Endocytosis involves bringing things into the cell through the formation of vesicles.

• Exocytosis involves moving things out of the cell which is also done through the formation of vesicles.

Endocytosis & Exocytosis

• There are three ways that endocytosis operates within a cell:

– Pinocytosis

– Phagocytosis

– Receptor-

mediated

endocytosis

Endocytosis & Exocytosis in Infection• Many pathogens enter the host cell through the formation of

vesicles.• This method provides protection for the pathogen from the

host immune response.• Some pathogens bind to host cell receptors that trigger

endocytosis. This is particularly true of viruses.

EUKARYOTIC CELLS: Role of Endocytosis & Exocytosis in Infection

• Phagocytosis is a type of endocytosis that can be used to defend against infection.

• Many pathogens have found ways to defeat phagocytosis.