Microorganisms Flashcards
What are five different organisms types that cause infectious disease?
Bacteria
Viruses
Fungi
Parasites
Prions
What is an infection/infectious
disease?
The invasion, multiplication and establishment of one (or more) pathogens (microorganisms/microbes) in the body.
Infections can begin anywhere in the body and may spread all through it – so causing disease (Which can be localised, or systemic)
Definitions of the following terms…
Pathogen, pathogenicity, virulence and pathogenesis.
Pathogen: any organism which can inflict damage/disease on the host.
Pathogenicity: The ability of an organism to inflict damage on the host (all or nothing)
Virulence: The relative ability of a pathogenic organism to cause disease (sliding scale)
– Virulence factors: genes, molecules, or structures that contribute to virulence
Pathogenesis: Mechanism of disease production.
What is microbial colonization?
Colonisation is when microorganisms, including those that may be pathogenic, are present at a body site (E.g. on the skin, mouth, intestines or airway) but are doing no harm and are not causing symptoms of infection.
The person colonised can also be called ‘a carrier’.
Definition of the following terms - Functional classification of microorganisms.
When do microorganisms cause disease?
EITHER…
1. Host defences fail to control organisms
AND/OR
2. Organisms overcome host defences
If neither of these happen, then you have colonization
What is the iceberg concept of infectious disease?
Spectrum of disease – biological response gradient – no symptoms to severe symptoms
Vast majority of interactions are thought to cause sub-clinical/mild symptoms - do not present
Is the speed of an immune response important?
Yes, speed matters!
Ability for the body to respond quickly has important implications for avoiding infection - late response = more replication/proliferation = disease
What are three examples of physical 1st line defences to pathogens?
What are three examples of physiological host defences against pathogens?
How do phagocytic/endocytic host defences help to fight off pathogens?
How does the inflammatory response help to fight off pathogens (real general terms)?
What are virulence factors?
Genes, molecules, or structures that contribute to virulence
What is Staphylococcus aureus? What type of infection is it responsible for?
Gram positive bacteria
Most virulent species of the genus staphylococcus - Pyogenic and/or toxin related disease (Toxic shock syndrome,
scalded skin syndrome).
Major pathogen in community and hospital acquired infection (surgical site infection & MRSA)
Responsible for…
1. Superficial ( e.g. skin and soft tissue) infections
AND
2. Deep seated infections (bacteraemias, endocarditis, osteomyelitis).
How does S. Aureus infection occur?
S. Aureus
1. Colonise the nasal cavity prior to infection
2. Nasal colonies spread and are the casual agent of infection
Different sites of infection:
1. Anterior nares
2. Axilla
3. Perineum
4. Throat
5. GI tract
What are the virulence factors that aid S. Aureus’s virulence?
Outline how the body responds to a S. Aureus skin infection?
Forms abscess to contain bacteria - relies on PMNs and langerhan cells - also drive recruitment of adaptive immune cells and phagocytes
What characteristics do organisms that infect the respiratory tract have in common?
Successful pathogens must:
1. Adhere to epithelial cell surface
2. Inhibit ciliary action
3. Avoid destruction by alveolar macrophages.
What type of bacteria is Streptococcus pneumoniae? What type of infections does it cause?
Gram positive cocci (purple)
Colonization: Nasopharynx and throat.
Leading cause of bacterial community acquired pneumonia
Infections:
Mucosal (upper airways): Sinusitis, otitis media
Pneumonia
Invasive: Bacteraemia (blood stream), Meningitis.
What virulence factors aid S. Pneumoniae’s virulence?
What are the three different sites of potential S. pneumoniae infection?
Colonisation of the upper airway - neuraminidase allows it to cleave mucins in the mucus
- Local spread of infection - Otitis media (ear) or sinusitis
- Moves down into the lungs - pneumonia
- Moves into the blood - Bacteraemia & Meningitis.
What are some immune defences located along the GI tract - mouth, stomach, small intestine and large intestine?
What barriers exist in the bladder to prevent infection?
Bladder:
1. Regular flushing action
2. Acidity of urine
3. Urine normally ‘sterile’
4. Urothelial cells covered in protective mucous
What is Uropathogenic E. Coli?
Rod-shaped, motile bacteria. Gram negative.
E. coli, part of gut microbiome, that has gained access to the urinary system from colonisation of periurethral area (tissues surrounding the urethra) then ascend the urethra to bladder.
Multiplication of bacteria and adherence to bladder causes cystitis.
Occasionally, E.coli can ascend further up via ureters to kidneys to cause pyelonephritis .
What type of virulence factors help Uropathogenic Escherichia coli?
Siderophores - used to scavange iron from the envirnment
What is Neisseria meningitidis? What type of diseases is it associated with?
Gram negative cocci
Carried in nasopharynx of approximately 5- 10% population
Note
Meningococcemia – sepsis
How does N. Meningitidis infection occur?
- Binding and entry at the nasopharynx
- Enters blood stream
- Cross blood brain barrier to enter CSF
Answer the following questions:
Why are hospitilised patients at greater risk of infection?
Hospitalized patients at great risk for new infections:
Host factors-
1. Vulnerable- immunocompromised,
2. Impaired swallowing (e.g. stroke/intubation etc), surgical procedures
3. Breach in physical defences- e.g. cannulation, urinary catheterisation.
4. Prosthetic material
5. Loss of microbiome- antibiotics
6. Loss of cellular immunity- e.g. chemotherapy, underlying illness.
What are four common types of hospital acquired infection?
Pneumonia- S. pneumoniae initially then greater variation e.g. Gram negative bacteria.
Surgical site infections - S. aureus including MRSA but also other
pathogens
Urinary tract infections- E. coli but also other pathogens e.g. proteus etc.
C. difficile infections - loss of microbiome in bowel.
Do microbes exist in a complex relationship with humans?
Yes, humans are not sterile - we have many symbiotic relationship that are important for life to function
We provide nutrients, space, temperature
Microbes help digest food, produce proteins, maintain the immune system and compete against each other for the Niche
Some sites are heavily colonised by microbes (GI tract), others are significantly more sterile (Brain, heart, liver, Bone & bone marrow and Joints) - presence of bacteria is indicative of illness
Is pathogencity a black or white concept - i.e. one microbe is always pathogenic whereas the another is not?
Nope - technically any microorganism capable of causing disease is a pathogen
Hence, although in health many commensals are beneficial under different circumstances, i.e. in disease, they may become pathogenic.
Pathogenicity is not black/white – depends on site, timing, quantity, etc.
Even for obligate pathogens - several factors need to fall into place in order to cause disease
What are…
Commensal microbes?
Obligate pathogens?
Zoonotic pathogens?
Environmental pathogens?
Commensals: Commensal microbes act on the host’s immune system to induce protective responses that prevent colonization and invasion by pathogens
Obligate: Obligate pathogens require a host to fulfil their life cycle
Zoonotic: A microorganism that is a colonizer of pathogen in animals - Transmitted to humans via direct vector or with direct contact with the animal or its products
Environmental: A microorganism able to cause disease transmitted to humans from an environmental source such as water or soil
What are the four stages of transmission by which pathogens enter/exit a host?
- Escape from the host or
reservoir - inside our body, animals, environmental sources, etc. - Transport to the new host - droplets, vector - mosquitos, direct contact, airborne, etc.
- Entry - causing clinical infection
- Escape - further spread
What is the definition of incubation time?
Incubation times time from infection to symptom development – highly variable
Range: few hours (food poisoning) to decades: Tuberculosis
The infected host can be infectious
What tissues do pathogens normally use to spread through the body?
Spread through the body
- Blood
- Lymph and blood
- Nerves
- Cerebrospinal fluid
What does the exit site of a pathogen normally correspond to?
Portal of exit is the path used by the pathogen to leave the host
Usually corresponds to the site where the pathogen is located
What four general strategies are adopted by pathogens to avoid the immune system?
Strategies for evading host defenses:
1. Concealment of antigens
2. Intracellular persistence
3. Colonizing privileged sites
4. Concealment by taking up host membranes or molecules
Example - clinical presentation of Neisseria meningitidis.
- Common in students
- Symptoms - generalised headache (not helped with analgesics), nauseated, feeling uncomforatble, muscle aches and feeling hot/shivery
- Non-Blanching rash
- Examination - flushed, cold, tachycardic, clear chest and neck stiffness
Example - clinical presentation of Staphylococcus aureus.
Case - Peter
Symptoms - two week history of fever and shortness of breath.
PMH: IVDU, unemployed and no allergies
Blood cultures - gram-positive cocci
Echocardiogram - vegetation in the aortic valve - bacterial colonising the valve region
Example - clinical presentation of Uropathogenic E. Coli.
Abigail - 60 year old
- Presented with a one week history of fever, back pain (kidneys)
- She also has had pain while passing urine and frequency.
- She is diabetic (increased risk of UTI)
E. coli - common cause of urinary tract infections
- Lower urinary tract infection (bladder
and urethra)
- Upper UTI (ascending to ureter/kidneys) – pyelonethritis, renal abscess.
What are the different factors that influence microbiome development between years 1-3 of life?
What role does the microbiome play in breast milk digestion?
Breast milk - Rich in human milk oligosaccharides (HMO)
Bifidobacterium longum infantis contains all the enzymes required for HMO digestion
This releases short chain fatty acids (SFCA), which then provide energy for intestinal cells
and promotes production of anti-inflammatory molecules
B. infantis also produces sialic acid required for brain development
What are factors that influence the adult microbiome?
- Anything we come into contact with - share microbiota with your household, environment, pets and food
- Altered by antibiotics
- Reduces in variety as we age
List some of the roles that the microbiome plays in host physiology.
Outline the role of the microbiome in energy biogenesis.
Resistant starch broken down by the microbiome to SCFAs (fermentation)
Produces: Butyrate, pyruvate, acetate
Impact of SCFAs on physiology:
1. Butyrate main energy source for enterocyte
2. SFCAs have anti-inflammatory and anti-tumour properties
3. SFCAs stimulate production of protein YY (PYY) - Induces satiety
Outline the role of the microbiome in protecting against pathogenic bacteria.
Healthy microbiome plays an important role in niche competition and nutrient depletion from invading bacteria - e.g. there is a heavy competition for colonising the epithelial surface/attachment to cell surface receptors
Ways that the microbiome protects…
1. SFCAs inhibit virulence gene expression and lower pH to below optimal growth conditions
3. Microbiota produce bacteriocins - Directly kill Salmonella, Listeria, Clostridium
What is the gut-brain axis - how is it linked to disease?
Gut brain axis - Neural connections involving central, autonomic and enteral nervous system
Strong links between GI disease and brain disease, e.g.
1. Depression, anxiety and GI symptoms
2. Irritable bowel syndrome
Potential involvement in CNS disorders
1. Parkinson’s
2. Alzheimer Disease
3. Multiple Sclerosis
Outline the role of the microbiome in bile metabolism.
Secondary bile acids have shown to have numerous impacts:
Shown to activate cell surface and nuclear hormone receptors - Hepatocytes, Intestinal cells, Inflammatory cells
Important in maintaining normal health:
1. Reduce gut inflammation
2. Regulate synthesis of bile acids
3. Activate vitamin D receptor
Also shown to stimulates glucagon like peptide-1 - Increases insulin secretion, reduces glucagon secretion
What are 5 diseases that have been associated with an altered microbiome?
A number of studies has identified associations between altered microbiome and disease:
- Obesity
- Type 2 diabetes mellitus
- Inflammatory bowel disease
- Colon cancer
- Asthma
How is the microbiome potentially linked to obesity?
Many reasons to consider the microbiome to be important in obesity
- Bacteria involved in energy production
- Stimulates production of mediators that alter insulin and glucagon production
- Involved in satiety
- Regulate intestinal integrity and inflammation
Supported by germ-free mice and microbiome transfer studies.
Human studies - Lean subjects have more bacteroidetes and it is linked with more weight loss
Outline the role of the microbiome in inflammatory bowel disease.
Two major conditions
1. Ulcerative colitis: affects the colon
2. Crohn’s disease: can affect any part of gut from mouth to anus
Both have chronic inflammation, relapsing and remitting - Usually treated by suppressing the immune system
Changes in the microbiome observed
1. Decreased microbial diversity
2. Some bacteria are decreased - Firmicutes, some Clostridium species
3. Some bacteria are increased
Enterobacteriaceae, including E.Coli
Facultative anaerobes (increases due to increased nitrosative and oxidative stress)
What treatments are used for inflammatory bowel disease?
Outline the changes seen in the microbiome of colon cancer patients.
Colon cancer linked with obesity, insulin resistance, red meat consumption, protected by fibre intake and increased exercise - could the microbiome be mediating these changes
Microbiome differs in patients in colon cancer - Cause or effect?
1. Seven bacterial species consistently elevated - Bacteroides fragilis-produces a tumorigenic toxin
2. Large number of bacteria are reduced
3. Also changes in the virome
Outline ways in which the microbiome may be protective and harmful towards colon cancer.
Metabolic output of the microbiome likely to alter risk of development and progression of colorectal cancer
Is there strong evidence for probiotics as a treatment?
Nope not really - maybe in type 2 diabetes.
What is Helicobacter pylori? How does it infect the stomach?
Helicobacter pylori can be found in the gastric mucosa (attached)
- Most common chronic bacterial infection in humans
- It is estimated that 50% of human population is infected
- Most commonly acquired in childhood
It is able to survive in the gastric mucosa as it…
- Has the enzyme urease which breaks down urea to produce ammonia which neutralizes gastric acidity
Outline H. Pylori’s infection pathophysiology.
- Attaches to the gastric mucosa
- Disrupts gastric mucus layer leading to exposure of mucosa to acidic environment
- Promotes inflammatory immune response
- Causes chronic gastritis (inflammation of the stomach lining) - This may be asymptomatic, But can lead to peptic ulceration!
- Leads to an overall increased risk of stomach cancer
Presentation of peptic ulcer disease?
Often asymptomatic but may cause bleeding leading to anaemia
Symptoms
1. Upper abdominal pain
2. Indigestion
3. Heartburn
4. Occasionally they perforate causing severe pain
What investigations and treatments are used for H. Pylori infections?
Investigation
1. Urea breath test - Give carbon-14 labeled urea and detect labelled CO2 in breath
2. Stool antigen test
3. Endoscopy and biopsy
Treatment
1. Proton pump inhibitor (e.g. lansoprazole)
- Suppress acid secretion
2. Antibiotics 7 day course
Amoxicillin and clarithromycin or metronidazole
What is clostridioides difficile? What type of GI infection is it associated with?
Clostridioides difficile - known for causing that causes diarrhea and colitis (inflammation of the colon)
Importantly, it is associated with antibiotic associated colitis:
Antibiotic use results in a change in the microbiome. Given that C. Difficile is resistant, it is able to proliferate and cause disease - produces a toxin that damages the epithelium (Toxin A & B)
How can one prevent and treat C. diff infections?
Prevention:
1. Choice of antibiotics - Some antibiotics are more likely to cause C. Diff infection e.g. ciprofloxacin, clindamycin, cephalosporins
2. Infection control measures
Treatment
1. Most cases respond to antibiotic treatment e.g. vancomycin or metronidazole
Note - some are resistant and/or recurrent
2. New treatment - fecal mass transplant - transplanting healty stool into a recipient - reserved for patients with recurrent disease
- Delivery via - Oral capsule, nasojejunal or nasoduodenal tube, enema and colonoscopy
What is the chain of infection?
What are the different modes of transmission?
How does direct contact transmission work? What are some examples?
Direct contact:
- Skin-to-skin contact, kissing, and sexual intercourse.
Example
a) Infectious mononucleosis (CMV) - “Kissing disease”
b) Methicillin-resistant S. aureus (MRSA ) - Contact with soil or vegetation harbouring infectious organisms.
- Hookworm contact with contaminated soil
- Clostridium botulinum
How does droplet spread work? What are some examples?
Direct transmission - Droplet spread:
Spray of relatively large, short-range aerosols produced by: sneezing, coughing, and even talking.
Transmission by direct spray over a few feet, before droplets fall to the ground.
Examples
- Meningococcal sepsis
- Bordetella pertussis – Whooping cough
How does airborne transmission work? What are some examples?
Indirect transmission - Airborne transmission:
Infectious agents are carried by dust or droplet nuclei suspended in air.
Droplet nuclei: Dried residue of less than 5 microns in size. It can remain suspended in the air for long periods of time and could be blown over long distance
Examples
Measles
Tuberculosis
How does vehicle transmission work? What are some examples?
Indirect transmission – Vehicles
Vehicle passively carries a pathogen: by providing the appropriate environment in which the organism grows and multiplies
Examples:
1. Food: Hepatitis A virus, norovirus
2. Water: Entamoeba histolytica, Legionella pneumophila
3. Biologic products (blood): HIV, Hepatitis B and C virus
4. Fomites (inanimate objects uch as handkerchiefs, bedding, or surgical scalpels).
5. Improperly canned foods: botulinum toxin by Clostridium botulinum.
How does vector transmission work? What are some examples?
Indirect transmission - Vectors:
Mosquitoes, fleas, and ticks may carry an infectious agent through:
- Mechanical means:
» Fleas – Yersinia pestis – agents carrying bubonic plague - Biologic transmission:
» Malaria: Plasmodium matures in an intermediate host before it can be transmitted to humans
What are different types of interventions that are used to block the chain of transmission?
Controlling or eliminating the agent at the source:
1. Antimicrobial treatment
2. Isolating the infected patient
3. Soil might be covered
Mode of transmission:
1. Water treatment
2. Hand washing
3. Modification of air pressure / quality – filters
4. Controlling vectors – mosquitoes
Portals of entry:
1. Use of Personal protective equipment (PPE): masks, gloves
2. Bed nets in zones of malaria
Increasing host defenses:
1. Vaccination
2. Prophylactic use of medication - antimalarials
3. Herd immunity
What is the aim of Infection Prevention & Control? How do they acheive this aim?
The aim of the IPCT is to minimise the risk of infection acquisition or transmission through a range of activities:
- Surveillance
- Policy & guidance
- Education & training
- Advice & clinical review
- Audit & quality improvement
What are some example of common healthcare-associated infections that can be prevented?
What is the public health act? Why is it relevant to doctors?
Duty to contact public health within three days if there is an infectious disease
Urgency of the matter is dependant on…
1. The nature of the suspected disease
2. Ease of transmission
3. Patient’s circumstances
4. Additional guidance provided by Scottish Ministers
What is the difference between active and passive immunisation?
Immunity is the ability of the body to protect itself from infectious disease:
It can be….
Innate or Acquired
Acquired
1. Active:
- Involves cellular and antibody responses
- Produced by patient’s own immune system – long lasting
- Can be acquired by natural disease or vaccination
2. Passive:
Protection by transfer of antibodies from immune individuals across the placenta or from transfusion of blood or blood products such as immunoglobulin
