Bacteria in the body

Question 1

Define infection

Answer 1

The successful multiplication of an organism within the host. Infection occurs when a microbe enters your body

Question 2

Define colonisation

Answer 2

Establishment of a site of microbial reproduction on or within a host. Colonisation
does not necessarily result in tissue invasion, damage or disease.

Question 3

Define infectious disease

Answer 3

An infection that produces signs and symptoms.

Question 4

Define pathogen

Answer 4

A microorganism that has the capacity to cause disease or A pathogen is a harmful microbe that causes infection and disease.

Question 5

Define virulence

Answer 5

A measure of pathogenicity, or the likelihood of causing disease

Question 6

Define virulence factor

Answer 6

A bacterial factor or strategy that contributes to virulence

Question 7

List and define the virulence factors

Answer 7

Virulence is mediated by virulence factors – components of a pathogen that damage the host:
- adhesins: coordinate binding of a microbe to host cell
- invasins: enable microbe to invade a host cell
- impedins: enable microbe to avoid host defence mechanisms
- aggresins: cause direct damage to host
- modulins: cause damage to host indirectly

Question 8

Describe the various bacterial forms found in the body

Answer 8

Extracellular bacteria:
These forms of bacteria do not invade cells and proliferate instead in extracellular environment e.g. V. cholerae adheres to epithelial surfaces and causes disease by secreting potent toxins e.g. rips in mucous lining

Intracellular bacteria:
Intracellular bacteria invade cells and proliferate them because:
- they are obligate, and require host products for growth (and cannot reproduce outside) and can only reproduce when inside cell e.g. Chlamydia
- bacteria can also be facultative, providing them with a selective advantage, benefit from intracellular location, but it is not obligatory e.g. Salmonella, invade intestinal epithelium and use macrophages to spread via lymphatic ducts of intestines to bloodstream to colonise liver, spleen

Abscesses: a painful collection of pus comprising dead tissue, WBCs and bacteria (can occur anywhere in the body)

Bacterial endospores or ‘senescent bacteria’:
Bacterial endospores is dormant, tough and non-reproductive structures that assist in transmission. They can enter the body through ingestion, inhalation and skin abrasions.

Question 9

Define endospore

Answer 9

Bacterial endospores or ‘senescent bacteria’:
Bacterial endospores is dormant, tough and non-reproductive structures that assist in transmission. They can enter the body through ingestion, inhalation and skin abrasions.

The structure of bacterial endospores is complex and multi-layered, and has 10-30% of the water content of a vegetative cell.

Some characteristics of bacterial endospores:
- increased survival in harsh environments
- increased viability on inanimate surfaces
- increased resistance to drying, radiation, chemicals e.g. acid and disinfectants
- increased heat resistance
- antibiotics are as useless as they are inert

Question 10

Describe the processes of endospore formation and germination

Answer 10

Endospore Formation
- Usually triggered by unfavourable conditions such as:
- Depleted nutrients
- Exposure of anaerobes to oxygen

Endospore germination is the irreversible conversion of endospore into a vegetative cell. It consists of 3 steps:
1. Activation: Requires appropriate trigger (increased temperature)
2. Germination: Requires appropriate trigger (increased nutrients, bile salts in small intestine.
3. Outgrowth: cell swelling and emergence, uptake of water, synthesis of RNA, DNA and proteins.

Question 11

List some examples of endospore forming bacteria

Answer 11

Endospores formed largely by Gram-positive bacteria (and a small number of Gram-negative bacteria). Many disease-causing toxin-producing bacteria form spores.

Bacillus spp.:
- Bacillus cereus – Emetic toxin
- Bacillus anthracis – Anthrax toxin

Clostridium spp. :
- Clostridium botulinum – Botulinum toxin
- Clostridium tetani – Tetanus toxin
- Clostridium difficile – Toxins A and B
- Clostridium perfringens – Enterotoxin

Question 12

What are biofilms and what is the advantage of forming a biofilm?

Answer 12

• Biofilms are aggregations of multiple microorganisms that secrete extracellular polymeric substances to form a protective matrix that adheres to biotic and abiotic surfaces
• Biofilms are usually composed of mixed species, but could be singular
  
  • Detachment of cells or biofilm aggregates may result in bloodstream or urinary tract infections.
  • Cells in biofilms have dramatically reduced susceptibility to antimicrobial agents.
  • Biofilms are resistant to host immune system clearance.

Requirements for a successful bacterial infection:
- enter host
- establish infection
- defeat host defences
- damage host
- exit host/transmit to another host

Question 13

Describe the broad requirements for a successful bacterial infection

Answer 13

Requirements for a successful bacterial infection:
- enter host
- establish infection
- defeat host defences
- damage host
- exit host/transmit to another host

Question 14

Define normal flora and where they can be found

Answer 14

Normal flora are microorganisms found on or in the body of healthy individuals ^[Bacterial cell to human cell ratio 1:1]. They compete with pathogens for space and nutrients. Normal flora are important for building immune tolerance and have a major role in health (diversity of normal flora is a sign of good health).

Examples of normal flora sites include:
- skin
- nose
- mouth
- URT
- small intestine (high concentration of bacteria here)
- large intestine (high concentration of bacteria here)
- urethra
- female genital tract

Question 15

Describe mechanisms of entry

Answer 15

Bacterial entry
- Entry of a pathogen is a primary requirement for exogenous infection and disease
- Normal flora can sometimes cause endogenous infection/disease i.e. an opportunistic infection, because they are already present in the body e.g. C.difficile ^[release toxins causing damage, usually kept in control by normal flora, fungus etc.. Meds also abolish flora which allows for proliferation]
- Any point at which pathogens can enter body is called a portal of entry
- Portal include mucous membranes, skin and parenteral

Portals of entry/mechanism of entry used by bacteria:
- respiratory tract (inhalation)
- GIT (ingested of contaminated food or water)
- GUT (abrasions in tissue, sharing bodily fluids^)
- Skin (cuts, abrasions, tears, hair follicles, perspiration ducts)
- parenteral (outside alimentary tract i.e. injections, surgery, insect and animal bites e.g. Y. pestis)

Question 16

Describe how bacteria establish infection

Answer 16

After entry, bacterial pathogens must find a way to stay in the host if it is to establish an infection. Adhesion of bacteria to host is an important prerequisite for colonisation and infection.

Bacteria can adhere to cellular surfaces (host cells and or specific receptors on host cells, or other bacteria), acellular surfaces (mucous, ECCM collagen, fibronectin, fibrinogen, laminin, heparin etc.), and static structures (indwelling urinary catheter/biofilm, mineralised bones and teeth/dental plaque biofilm).

Given adhesion of bacteria to host requires physical contact, it is not surprising that these interactions have a plethora of consequences.

Question 17

Describe bacterial adhesion and the different factors that contribute to adhesion

Answer 17

There are several bacterial factors that contribute to adhesion. They include:
- pili, which are multi-subunit protein polymers that form long hair-like appendages. There are approximately 10 pili per cell
- Fimbriae are specialised adherence structures made of multi-subunit protein polymers. Fimbriae are fine bristle-like appendages. There are up to 1000 fimbriae per cell.
- S-layer is a proteinaceous outermost cell envelope component involved in adherence.
- Flagella are macromolecular, multi-component structures. Its primary function is motility but it also aids in adherence.
- Capsules are made of a layer of exopolysaccharide surrounding bacteria that aids in adherence. An example is the Streptococcus mutans produces dextran polysaccharide capsule allowing binding to the tooth surface, which causes dental carries.
- Outer surface and membrane proteins are specific adherence proteins. An example is the M-protein on the surface of Streptococcus pyogenes which binds receptors on the respiratory mucosa.
- Wall teichoic and lipoteichoic acids are gram-positive bacteria cell wall structures.
- Peptidoglycan
- LPS

Question 18

Explain how the lock and key theory applies to bacterial adherence

Answer 18

The specific ‘lock-and-key’ adherence of bacteria to biotic surfaces requires the participation of two complementary factors:
- adhesion: a surface structure that binds a bacterium to a specific surface
- receptor: a complementary binding site on the surface of the host that binds specific adhesins

Question 19

List some examples of host receptors for bacterial adhesion

Answer 19

• TM proteins
• ECM molecules associated with host cell membrane
• glycoproteins
• glycolipids
• phospholipids
• receptors e.g. for cytokes, hormones, Igs, ECM molecules

Question 20

Explain an alternate mechanisms by which bacteria adhere to cells

Answer 20

Attractive forces
The non-specific adherence of bacteria to biotic or abiotic surfaces. Bacteria adhesion can occur via hydrophobic interactions or cation-bridging

Question 21

Define cellular tropism and provide some examples of the tropism of certain bacteria

Answer 21

-propensity to infect certain tissue types
e.g. Neisseria gonorrhoeae and GUT, gonorhea
Strep. pyognes, respiratory epithelium AND pharyngitis
Step. pneumoniae, RT epithelium AND pneumoniae
Clos. tetani. inhibitory interneuron, tetanus

Question 22

Does colonisation necessarily result in disease? Why or why not?

Answer 22

• Bacterial replication is vital requirement for a successful bacterial infection.
• Doubling time for some bacteria can be as little as 20 minutes (rapid increase in organisms can quickly overwhelm a human host).
• Bacteria colonisation results in the establishment of a site of microbial replication within the host.
• Colonisation does not necessarily result in tissue invasion, damage or disease

Question 23

Describe mechanisms by which bacteria can move

Answer 23

Motility:
- Flagella facilitate bacterial movement
- Allow bacteria to move towards a cell, within a cell

Chemotaxis:
- Bacteria can move to mucosal surface as a result of chemotactic responses
- Chemoreceptors in the cell wall facilitate response to chemotactic molecules.

Question 24

List some startegies and virulence factors used by bacteria to invade the host

Answer 24

A vast number of strategies are used by bacteria to invade deeper, underlying tissue to further establish infection. aka invasins

Examples of virulence factors that aid in bacterial invasion include:
- Hyaluronidase
- Coagulase
- Streptokinase
- Nuclease
- Lipase

Question 25

List some mechanisms of bacterial dissemination

Answer 25

Dissemination can cause infections in other regions of the body and can have implications in other regions of the body unrelated to the primary site of infection.
Mechanisms involved include cell-cell spread, infection of macrophages and spread through the lymphatics, haematogenous spread, congenital, local and systemic dissemination of bacterial toxins, trauma and abscesses.

Question 26

Provide some examples of bacterial anti-host defence mechanisms

Answer 26

If pathogen manages to get into a host, stay in, and rapidly increase its numbers, it’s on the way
to causing a successful infection.
But pathogen has to deal with host defences using:
- Structure of the pathogen cells (a passive defense)
- e.g. Biofilms and capsules enable evasion of phagocytosis
- Streptococcus pneumoniae and Klebsiella pneumoniae will not cause bacterial pneumonia when non-encapsulated.
- Attacking the host’s defenses (an active defense)
- Streptococcal and Staphylococcal leukocidins are enzymes that destroy white blood cells in the host.
- Streptococcus pneumoniae Secretory IgA (sIgA) protease destroys sIgA which is secreted into host mucous layers and binds to bacterial antigens to neutralise infection and promote bacterial clearance.

AKA impedins and aggressins

Question 27

List the two types of bacterial-induced host damage

Answer 27

Most of damage associated with infection can be divided into two parts:
- Damage that occurs because bacteria are present
- Damage that is a by-product of the host response

Damage directly attributable to pathogen can be either direct or indirect:
- Modulins: Cause damage to host indirectly
e.g. Lipid A component of LPS stimulates potent proinflammatory cytokine response that can lead to septic shock (inflammation, fever, sweating vessel dilation, hypotension, coagulation, organ failure)

• Aggressins: Cause direct damage to host
  e.g. Bacterial exotoxins

Question 28

Define exotoxins and their various mechanisms

Answer 28

Exotoxins are soluble proteins secreted by some species of bacteria that directly damage the host and promote the spread of infection.

Can attack different cell types:
- Enterotoxins à intestinal cells
- Neurotoxins à neuronal cells
- Leukotoxins à white blood cells
- Cytotoxins à broad range of cell types

Can act through specific mechanisms:
- Botulinum toxin (C. botulinum): blocks neurotransmitter release, leading to paralysis
- Streptolysin O (S. pyogenes): haemolysis
- Pertussis toxin (B. pertussis): reduces ATP and increases cAMP, leading to cell death
- Shiga toxin (S. dysenteriae): inhibits protein synthesis, leading to cell death

Pathogens have multiple specific virulence factors that allow them to cause disease. The diagram shows an example of the multiple virulence factors of Salmonella.
- enterotoxin causing diarrhea aggresins
- cytotoxin
- fimbriae adherins
- O antigen inhibits phagocyte killing impedin?
- endotoin , fever, in LPS
- flagellum, adherin, impedin

Question 29

Explain what the difference between infection and infectious disease is

Answer 29

Infection occurs when a microbe enters your body.
Disease occurs when host sustains sufficient damage to perturb homeostasis.

Question 30

Describe the factors influencing damage as a result of infection with a microbe

Answer 30

Damage is mediated by the pathogen or the host (or both) i.e. damage can result from direct microbial action or the host immune response (or both)

Question 31

Describe the form that extracellular bacteria take in the body

Answer 31

These forms of bacteria do not invade cells and proliferate instead in extracellular environment e.g. V. cholerae adheres to epithelial surfaces and causes disease by secreting potent toxins e.g. rips in mucous lining

• plaque/biofilms

Question 32

Explain why intracellular bacteria invade and proliferate inside cells

Answer 32

Intracellular bacteria invade cells and proliferate them because:
- they are obligate, and require host products for growth (and cannot reproduce outside) and can only reproduce when inside cell e.g. Chlamydia
- bacteria can also be facultative, providing them with a selective advantage, benefit from intracellular location, but it is not obligatory e.g. Salmonella, invade intestinal epithelium and use macrophages to spread via lymphatic ducts of intestines to bloodstream to colonise liver, spleen

Question 33

Define abscess

Answer 33

a painful collection of pus comprising dead tissue, WBCs and bacteria (can occur anywhere in the body)

note dead neutrophils = pus

Question 34

Explain the importance of bacterial exit

Answer 34

This is the final requirement for a successful bacterial infection. Bacteria leave body and are transmitted to another host via a portal of exit, which is any point at which
microbe can leave body. Exit portals include respiratory tract, gastrointestinal tract, and the genitourinary tract.