Repiratory Tract: adhesion

Question 0

Pneumococcal infections

Answer 0

• globally important pathogen it causes a variety of localised and systemic infections, including pneumonia
• enter via nasopharynx and attach to epithelial cells
• 90 different serotypes - developed as a result of immune selection

Question 1

Bacteria community development

Answer 1

1) colonisation by pioneer species
2) outgrowth
3) secondary colonisation
4) production of a climax community

Question 2

Process

Answer 2

• progression to pneumonia results from spread of the pneumoccoci by aerosol from the nasopharynx down into the lower respiratory tract - adhesion
• s. Pneumonia produces peroxide to fights other bacteria but also damages its own genome which is why is has a high recombination rate by allowing non- component lysing
• H. Influenza infection neroamindase cleaves Salic acid and makes a carbon source for S. Pneumonia, making it a higher growth rate

Question 3

Epidemiology

Answer 3

S. Pneumoniae is the most common cause of community acquired pneumonia in previously healthy person

Question 4

Symptoms

Answer 4

• acute onset with seven systemic symptoms such as high fever, rigours, prostration and sometimes headaches and delirium. These are followed by pleuritic chest pain, cough and breathlessness
• chest X-ray generally shows an alveolar pattern of consolidation in a single lobe but sometimes more than one is affected and in a few cases the disease is confused to a single pulmonary signal

Question 5

Diagnosis

Answer 5

Is most reliably made by the isolation of the organism from the blood culture but this is successfully achieved in only 30% of cases

Question 6

Disease onset

Answer 6

• lesion is characterised by fluid filled alveoli containing pneumoccoci which are frequently see to line the alveolar walls
• access to the blood circulation from the alveolar space, suggesting an aggressive capacity to cross the vascular endothelial cells
• characterised by intense inflammation

Question 7

Receptors

Answer 7

• during the course of pneumoccal infections, the bacteria are presumed to attach to and interact primarily with nasopharyngeal cells, vascular endothelial cells and lung cells
• minimal receptor units have been defined on the basis of inhibition of adherence in vitro by competition experiments using simple and complex carbs

Question 8

Interaction

Answer 8

• NanA important virulence factor, cleaves Salic acid
• it decrease the viscosity of the mucus and exposes the GlcNAc receptors on the epithelial cell, which interact with pneumoccal surface associated proteins such as PsaA. In response to cytokine stimulation, host epithelial cells up regulate the PAFr
• it has increased affinity via its ChoP for PAFr
• CbpA shows increased affinity for immobilised Salic acid and lacto-N-neotreatose and binds directly to the polymeric Ig receptor which increases migration through mucosal barrier
• igA proteases cleaves opsonising igA which results in a change of surface charge and increases the physical proximity of Chop to PAFr

Question 9

Lipoprotein associated adhesions

Answer 9

• in bacteria solutes may be transported across the cytoplasmic membrane by via ABC type uptake systems. These are composed of one or two transmembrane proteins, one or two cytoplasmic ATP binding proteins and an extracellular solute binding protein
• in gram negative the solute binding protein is perplasmically located
• in gram positive bacteria the solute binding protein is modified by lipid at AA terminus, which anchors the polypeptide to the cell membrane
• although these lipoprotein are relatively small there is good evidence that they are exposed at the cell surface

Question 10

Cell wall associated proteins

Answer 10

• the surface exposed regions may contain binding sites for various human proteins
• signal peptide mediated export across the cytoplasmic membrane during this process the cell wall sorting is recognised
• the hydrophobic domain and the charged domain function to stop translocation of the polypeptide chain across the cytoplasmic membrane
• recognition of the LP x TG motif only occurs when it is correctly spaced relation to positive charged domain and then the sort ease cleaved the precursor between threonine and glycine of the motif and link the n terminal fragment to the bacterial cell wall
• cleavage of this pentaglycine crossbridge by lysostaphin releases cell wall linked proteins as a single species rather than a spectrum of sizes which suggests that this peptidoglycan cross bridge is the site of covalent linkage between surface proteins and the cell wall

Question 11

Experimental identification of host receptors

Answer 11

• adherence of pneumocci to pneumocytes increased ~30% and adherence to endothelial cells increased ~70% following cytokine stimulation
• enhanced adherence was associated with the appearance of new receptor specificity for GlcNAc
• change in adherence of pneumocci to activated cells illustrates an important initial attachment of pneumocci to resting cell involves one set of sugar specificities. Cells become rapidly activated and change the presentation of new receptors on their surfaces - virulent matches
• action and reaction underlies the success of virulent pathogens and illustrates the dynamic nature of the response of both partners in an adherence interaction

Question 12

Host Ligand to which adhesins bind

Answer 12

• N linked glycan > serum glycoproteins > high mannose, complex, hybrid
• O linked Glycans > submaxillary mucins and erythrocytes, bronchial, mucin from CF patients