Bacterial properties and disease

Question 1

Bacterial properties: explain the meaning of the following terms when describing bacterial structure and function; coccus, bacillus, rod, acid-fast

Answer 1

1. Coccus; spherical shape
2. Bacillus; rod shape
3. Acid-fast bacteria; are risistant to the Gram staining method and are therefore stained with the acid-fast stain method

• this is because theyhave a waxy substance called mycolic acid in their cell walls which makes them impermeable to many staining procedures (able to resist decolorization with acid alcohool)

Bacterial pathogens functions:

1. Colonize (surface structures such as pili)
2. Persist (avoid, subvert, or circumvent host defenses in or outside cells)
3. Replicate (acquire nutrients such as iron, energy sources etc)
4. Disseminate within cells, tissues between organs and hosts (bacterial and host cell motility, through aerosols, faeces etc)
5. Cause disease (produce toxins that kill host cells, induce diarrhea, dysregulate immune responses)

Question 2

Bacterial properties: explain the meaning of the following terms when describing bacterial structure and function; Gram-negative, Gram-positive

Answer 2

To distinguish between two cell types we use the Gram positive and Gram negative method.

Procedure; target is the peptidoglycan which is a polymer consisting of sugars and amino acids ( mesh like layer outside the plasma membrane)

1. Violet dye and iodine
2. alcohol rinse
3. red dye

Gram Positive Bacteria; there is only one cytoplasmic membrane which retains the dye and has a violet colour (thick peptidoglycan)

• Staphylococcus aureus, strep pneumoniae

Gram Negative Bacteria; there are two cytoplasmic membranes (difficult to get antibiotics through the wall), thinner peptidoglycan which loses the dye resulting in a pink colour

• E. Coli, salmonella, shigella

After Gram stain:

• Culture and microscopy
• Biochemical and serological tests
• Sensitivities to antibiotics
• DNA techniques: PCR, sequencing

Mycobacteria

Mycobacterium tuberculosis (TB)

Mycobacterium leprae (leprosy)

Question 3

Bacterial properties: explain the meaning of the following terms when describing bacterial structure and function; intra-cellular, extra-cellular

Answer 3

Extracellular Pathogens; Staphylococcus, Streptococcus, Neisseria, Yersinia

Intracellular Pathogens; once they enter the host cell there are inside endosomes or phagosome and there are three many ways they behave/react;

1. Formation of vacuole; prevents fusion with lysosomes
   
   • Salmonella, Chlamydia, Mycobacteria
2. Escape the endosomes or phagosome and move freely into the cytoplasm
   
   • Listerial, Shigella
3. Fuse with lysosomes to form a phagolysosome
   
   • Coxilla

Question 4

Bacterial gene transfer: compare the three main ways bacteria use to exchange genetic material

Answer 4

There are two main ways by which bacteria exchange genetic material;

Vertical gene transfer; bacteria replicate by binnary fussion

Horizontal gene transfer; which is further divided into 3 main mechanisms

1. Transformation; ability of the bacteria to take up naked DNA from the environment and intergrate it into the host genome (process of homologus recombintion)
   
   • Neisseria, Streptococcus
2. Transduction; accidental viral transfer of bacterial DNA. transduction phage ( viruses picks up some bacterial DNA) and bacteria phage ( viruses that affect bcteria)
   
   • Many gram +ve/-ve
3. Conjugation; direct transfer of bacterial DNA
   
   • this happens between F⁺ (have a sex pallet) and F^- (do not have a sex pallet) –> those 2 will form a mating bridge (conjugation)and the sex pallet will be transfered(plasmid)
   • Bacterial sex
   • Many gram +ve/-ve

Horizontally acquired DNA that contributes to virulence = A Pathogenicity Island

Question 5

Recall two related bacterial multi-protein machines and two examples of manipulation of host actin cytoskeleton

Answer 5

Multi-protein machines:

ex. Salmonella surface structures
1. Flagellum
* locomotion
1. Injectisome

• transfer of virulence proteins into host cells
• causes actin polymerisation, membrane ruffling, bacterial internalisation

Manipulation of host actin cytoskeleton:

1. Salmonella (injectisome)
2. Listeria - (causes food poisoning and more serious diseases in the immunocompromised, elderly and pregnant women) (image)

Question 6

Infectivity and virulence: explain the concepts of infectivity and virulence, and define the term infective dose

Answer 6

Pathogenicity of bacteria: (ability to cause disease)

Pathogens -True (Staph. aureus causing skin abscess) or Opportunistic (Staph. epidermidis causing prosthetic hip joint infection)

Factors affecting pathogenicity:

Infectivity: The ability of a pathogen to establish an infection

Process of invasion;

1. Transmission to host
2. Colonisation; using surface structures (pili)
3. Tropism – find the right niche
4. Replicate; by acquiring nutrients
5. Disseminate; within cells, tissues and organs
6. Evade immune system; produce toxins that kill host cell

Virulence: The ability of a pathogen to cause disease

1. Toxin production
2. Degrading enzymes
3. Interruption of host cell processes
4. Complete immune evasion

Infective dose; Number of bacteria required to initiate an infection –>Measured in CFU (colony-forming units)

Influenced by;

1. Route of transmission
2. Ability to colonize host
3. Tropism and motility
4. Replication speed
5. Immune invasion

Examples:

• Mycobacterium TB 10 CFU highest
• Vibrio cholerae 10,000,000 CFU lowest infectivity

Question 7

Bacterial sources and routes: list the potential sources and possible routes of infection by bacteria

Answer 7

Sources of Bacteria

1. Extrinsic: usually come from other people and other living things (animals food and water)
2. Intrinsic; non-sterile sites (exist in our organisms) –> normal microbiota

Routes of infections;

1. Expected
   
   • Neonate and urogenital tract during childbirth
2. Unexpected
   
   • Surgery
3. Upper respiratory tract; mouth nose, nasal cavity
   
   • bacteria aquired that way are usually extrinsically transmitted from droplets. airbone etc
   • Viruses: Influenza, rhinoviruses
   • Bacteria: Streptococcus spp/ pneumonia
   • Causes pharyngitis, tonsilitis –> spreads to adjacent tissues (brain abscess, middle ear infection)–> spreads to lower respiratory tract –> spreads to bloodstream
4. Urogenital tract
   
   • Extrisnic; catheters, sexually transmitted and Intrinsic; bacteria from the large intestine
   • Pathogens of the genital tract: Large intestine (streptococcus group) or STD (chlamydia, HIV)
   • Urinary Tract Inf. –> spread to bloodstream
   • Genital infection –> pregnancy-related inf. –> spread to bloodstream
5. Broken skin
   
   • surgery wound, diseases, insect bites
   • infection via broken skin leads to ->
     
     • superficial infection
     • cellulitis
     • abscess
     • fasciitis
     • myositis
     • bacteremia
6. Gastro-intestinal tract (Faeco-oral route)

Question 8

Bacterial pathogens: list examples of important bacterial pathogens, explain how they are transmitted by different routes, and the ways in which they cause disease

Answer 8

Mouth

1. Streptococcus pyogenes -> tonsillitis
2. Meningococcal septicaemia

Respiratory tract – upper to lower

1. Streptococcus pneumoniae -> pneumonia
   (nasal sinuses and into brain)

Faeco-oral

1. Cholera - salt and water lost from the gut due to toxin released
   
   • Enormous infective dose 106- 1010
   • Flagella used to penetrate mucus
   • Then makes 2 component toxin A + B
   • Binds to GM gangliosides on gut
   • Triggers cyclicAMP
   • Chloride efflux
   • Na and water follow
   • Profuse diarrhoea “Rice water stools”

_GIT to urogenita_l (to neonates)

Through skin

1. Staphylococcus aureus – neutrophil killing toxin

Urinary Track; can be

1. limited to the bladder –> Cystitis
2. go up to the kidneys–> Pyelonephritis

Based on Gram staining;

Gram –ve:

1. Neisseria Meningitidis:
   
   • Respiratory, endotoxin that damages RBCs/causes shock.
   • Has polysaccharide capsule (anti-phagocytic)
2. E. Coli:
   
   • Food/water contamination, faecal-oral.
   • Toxin into blood stream via large intestine, kidney failure

Gram +ve:

1. Staphylococcus Aureus:
   
   • Respiratory
   • Release of enzymes & toxins – cause multiple symptoms

Question 9

Systemic inflammatory response syndrome: recall the disease continuum of the systemic inflammatory response syndrome

Answer 9

1. SIRS – systemic inflammatory response syndrome
2. Sepsis
3. Severe sepsis
4. Septic shock
5. MODS – multiple organ dysfunction syndrome

SIRS = systemic inflammatory response syndrome

Defined by a criteria:

1. Temperature - >38 or <36
2. Resting HR > 90
3. Resting respiratory rate > 20
4. WBC count >10,000 or <4,000

2 or more = SIRS

Question 10

Pathophysiology: explain the pathophysiology of sepsis

Answer 10

Sepsis ; SIRS+ Infection

Severe sepsis; Sepsis + lactic acidosis

Septic shock = severe sepsis + hypotension despite fluid results (shock = poor tissue perfusion)

Sepsis and septic shock are systemic inflammatory responses to infection which are caused by immune and vascular system overreaction and dysregulation

S&S criteria :

1. Skin colour/warmth
2. Pain
3. Mental ability
4. Breathing difficulty

Septic shock pathophysiology ;

1. WBC recruitment because of pathogens
2. Release of NO for increased permeability (allow cell to migrate into the tissue) /vasodilation ( reduce blood flow and allow cells to migrate)
3. Reduced BF contributes to shock
4. Increased permeability leads to fluid loss to interstitial space and therefore less perfusion and hypotension
5. Chemical release from WBC leads to endothelial damage -> permeability increases
6. Increases in CO to compensate for low TPR

videos;

https: //www.khanacademy.org/science/health-and-medicine/circulatory-system-diseases/shock/v/sepsis-sirs-mods
https: //www.khanacademy.org/science/health-and-medicine/circulatory-system-diseases/shock/v/septic-shock-pathophysiology-and-symptoms

Question 11

Sepsis treatment: describe the therapeutic strategies and patient support procedures during organ failure

Answer 11

1. Early detection is key
2. Target the infection

• Antibiotics – broad spectrum and then organism specific
• Blood products – more RBCs -> better perfusion

1. Try to increase the BP to prevent shock:
   
   1. Fluids
   2. Vasopressors

Question 12

Susceptibility: explain individual differences and the genetic role on susceptibility to infection

Answer 12

Factors Influencing:

1. Genetic
2. Microbiome – Gut, skin
3. Nutrition – Vit A
4. Social networks
5. Stress – negative effect
6. Splenectomy
7. Immunosuppression – transplant, autoimmune

genetic differences are covered in immunology but the main gebetic factor is HLA/MHC (determines which antigen is recognized)

Question 13

Therapeutic targets: identify pathways and targets for treatment of infection