L3 - Professional pathogens

What is the medical term for blood-stained sputum?

Haemoptysis

Define colonisation (KT)

Colonisation - when an organism lies on us but is not causing infection

LTA and peptidogycan recognition

G+ve bacteria don't have endotoxin Cell wall components: - Lipoteichoic acid - Peptidoglycans Can stimulate immune responses just like LPS but different TLRs

What is the bacterium in this sputum gram stain?

G+ve diplococci Pneumococcus with a diagnosis of pneumococcal pneumonia, commonest cause of pneumonia in the elderly

Explain what coagulase does, where it is located on the bacteria and how it can be used in a laboratory test. (KT*)

Coagulase is located on the surface of S.aureus. It stimulates clotting and plays a role in immune-evasion. There is a coagulase test which can be used to differentiate between staphylococcal bacteria, e.g. between S.aureus and S.epidermidis. The bacteria are added to sheep serum, a positive test (coagulation) = S. aureus

How does S.aureus food poisoning occur? What are the symptoms? (KT*)

Contamination of food Manufacture Preparation - Caused by S. aureus enterotoxins - Ingestion → Rapid brief illness, Vomiting +++, Minimal diarrhoea

Describe the relevance of the symptoms in this Case, would there be any tests you would undertake?

'Glass test'- identify non-blanching rash typical of meningococcal septicaemia

What bacteria is this?

C.diff

Describe the features of C.difficile. Where is it found? What infections can it cause?

- Gram positive rods - Anaerobic - Spore forming (non-vegetative state) - Soil - Gut (humans and animals) - Wound and GI infections - Antibiotic associated diarrhoea (up to 30%) - Very common as changes in gut flora - C. difficile resistant to many antibiotics - In elderly / debilitated patients on antibiotics C. difficile may 'overgrow' Whole range of diarrhoea - Mild - Severe 'pseudomembranous' colitis - Gut perforation and death

What are the mechanisms of Streptococcus pneumoniae's virulence

1) Adhesins - Adhesion and Cloaking 2) Toxins - Lysins - Tissue enzymes (elastase, collagenase, coagulase) - Exofoliative toxins, enterotoxins - Enzymes targeting host immune responses (IgAase) 3) Capsule 4) Endotoxin 5) LTA / Peptidoglycans

What are the 4 Clostridium species?

1) C. difficle 2) C. tetani 3) C. botulinum 4) C. welchii

What does Streptococcus pneumoniae cause?

1) Commonest form of pneumonia (~40%) 2) Disseminated disease: - Bacteraemia - Endocarditis (Infection of heart valves) - Upper Resp Tract Infections (Upper RTI) - Sinusitis - Otitis media - Meningitis

Outline the staphylococcal toxin types (3) with examples. Do all strains have these? (KT*)

1) Cytotoxins - Pore forming toxins, lyse host cells - Panton-valentine leukocidin (PVL) lyses polymorphs (kills neutrophils - normally esp. imp. In bacterial infection) 2) Exfoliative toxins - Proteases = Target epidermal structural proteins 3) Enterotoxins (superantigens) - Stimulate massive T cell activation ?immune evasion - Ingestion → vomiting Many of these are phage encoded - only present on a proportion of strains

Explain C.difficiles pathogenicity

1) Makes toxins - cause fluid secretion into gut - Diarrhoea - Increased infectivity 2) Production of spores - Difficult to control cross infection - Relapse on treatment 3) Some virulent strains (027) - antigenic profile - Lose regulation of toxin genes - hyper-producers - Produce additional toxins

So in clinical practice whether a germ is thought to be a pathogen vs commensal depends on

1. The immune status of the patient. 2. The site / sample in question. 3. The disease causing properties of the bacteria (virulence).

Define commensal (KT)

A commensal 'someone who eats with you' - an organism which lives on us / in our gut but doesn't cause infection.

Bacteria that can make ATP with or without oxygen are called __________

A facultative anaerobe is an organism that makes ATP by aerobic respiration if oxygen is present, but is capable of switching to fermentation or anaerobic respiration if oxygen is absent

Define pathogen (KT)

A pathogen - an organism which can evade the immune defences of the normal human host to cause infection. Pathogens may colonise before causing infection

Explain with examples, the differences between professional and opportunistic pathogens

A spectrum: Professional pathogens - almost always cause disease Opportunistic pathogens - only cause disease in immunocompromised patients This is because organisms vary in... Virulence -fundamental properties of the organism. If a patient is immunocompromised, low virulence organisms may be pathogens, for example S. epitdermidis and C.albicans which were not pathogenic on the above diagram are now shifted toward that end.

Virulence factors can aid differentiation from other strains. Explain what adhesins are with 3 examples. Explain what protein A is and how it enables immunoevasion.

Adhesins: bind host proteins - Tissue adherence - Immune evasion 'cloaking' e.g. Elastin BP, Collagen BP and Fibronectin BP. Protein A Binds the Fc portion of IgG i.e. it holds the Ig molecules the wrong way round attached to the bacterium

List three S.aureus skin infections with their appearance (KT*)

In addition, a central line can lead to infection of the skin by opportunistic infections

Define infection (KT)

Infection - when an organism enters the body, increases in number and damages the host in the process (invasion, replication, damage)

Explain the recognition of LPS by the innate immune system and what it results in. Why can people get very sick with G-ve infections? (KT*)

Innate immune system is very sensitive to LPS: - Evolution (probably) G-ve predominance in bites, contaminated wounds etc - Allows very early recognition of infection LPS interacts with TLRs (PAMP) (esp. TLR4) on: - Monocyte/macrophage lineage cells - Endothelium Results in activation of: - Inflammatory pathways - Coagulation and clotting pathways - Changes in endothelial integrity - to allow leakage Gram negative bacteria in the blood: - Endotoxin in the blood - Systemic activation of immune responses = Main reason why people get v. sick with G-ve inf.

Define opportunistic pathogens

Opportunistic pathogens - only cause disease in immunocompromised patients This is because organisms vary in... Virulence -fundamental properties of the organism

Define parasite (KT)

Parasite - unequal benefit, usually used for worms etc but true of all infections

Explain the difference between the terms 'virulence' and 'pathogenicity'

Pathogenicity: The probability that an organism is causing disease when its isolated from a patient. So pathogenicity relys on: - The organism's virulence, also... - Where it is: Blood, urine (normally sterile); Stool, throat (not normally sterile) - Immune state of the patient

Why is a capsule protective?

Polysaccharide capsule: - 'micro capsule' thin compared to other encapsulated bacteria Specific Abs to capsular antigens required because: - Ab-peptidoglycan binding is prevented by capsule = no-opsonisation - PMN Fc and complement receptors can't reach any opsonins. = no opsonisation

Define professional

Professional pathogens - almost always cause disease

What is the following colitis?

Severe 'pseudomembranous' colitis

Outline Streptococcus pneumoniae's virulence

Specific adhesins for respiratory mucosa 1) Pneumolysin - binds host cell membrane cholesterol - Forms pores and lyses in ciliated cells - Lyses host phagocytic cells 2) Secretory IgA protease - breaks down secreted immunoglobulin A, preventing mucosal clearance 3) Capsule - Polysaccharide coat prevents complement-mediated phagocytosis - Specific antibodies to capsule required - >100 different capsular types

Illustrate the major bacterial virulence mechanisms using specific examples such as Staphylococcus aureus. Use this information to explain the spectrum of disease caused by S. aureus.

Staphylococcus aureus: - Commensal of anterior nares in 20-60% - Highly adapted Species Adherence to nasal mucosa Adhesins Ability to invade tissues Cytotoxins Enzymes Ability to evade immune clearance Protein A (vs Ig) Capsule (polysaccharide) Ability to replicate and disseminate

Define symbiosis (KT)

Symbiosis - mutual benefit

Define virulence

Virulence -fundamental properties of the organism

What is the commonest cause of pneumonia in the elderly?

pneumococcal pneumonia ie. Streptococcus pneumoniae