Bacterial infection of the host

The infection process:

1.        Exposure to pathogens

2.        Adherence to skin/mucosa

3.        Invasion through epithelium

4.        Multiplication – growth and production of virulence factors and toxins

The disease process:

1.        Toxicity – toxin effects are local/systemic

OR

1.        Invasiveness – further growth of original and distant sites

2.        Tissue or systemic damage

Exposure – entry points:

-            Respiratory tract

-            Gastrointestinal tract

-            Urogenital tract

-            Breaks in the skin surface

Mucous membranes line the digestive, respiratory, and reproductive tracts. Ita a primary barrier protecting the body from the external world. It’s a key site of innate immune defence. It has no particular specificity for any one pathogen. There are several immune functions at the mucous membranes:

-            Lysozymes hydrolyse the bonds in the sugar backbone of the peptidoglycan

-            Mucociliary clearance helps expel inhales microbes from airways

-            Cationic antimicrobial peptides disrupt bacterial membranes

-            Mucosa-associated lymphoid tissue (MALT) provides accumulation of lymphocytes

Adherence:

Numerous bacterial components contribute to adherence, including:

-            Pili and fimbriae. They are short, hair-like projections that cover the cell. They are the bacterial cell structure that bind host cell surface glycoproteins. Pili are typically longer and fewer in number than fimbriae, and some pili also function in the process of conjugation.

-            Capsules. They are most commonly comprised of polysaccharides, located outside of the cell envelope. It can be found in both Gram positive and negative organisms. They promote attachment through specific molecular interactions, as well as being inherently ‘sticky’. They also contribute to immune evasion.

-            Lipoproteins. Membrane proteins that are anchored to membranes through an N-terminal lipid moiety attached to a conserved Cysteine.

Bacterial cells will possess multiple ‘adhesins’ that bind different host cell ligands.

Salmonella enterica, serovar Typhi (Salmonella typhi):

It’s a causative agent of typhoid fever. Type IV pili of S. typhi enable the attachment to epithelial cells, and subsequent entry. The pili bind to host CFTR protein (Cystic Fibrosis Transmembrane conductance Regulator). Numerous population genetic studies have confirmed a correlation between cftr polymorphisms and partial protection from typhoid fever

Adherence and biofilms:

Biofilms are an aggregate of bacterial cells attached to a surface and encased in a matrix. Matrix components are produced by the bacteria themselves. During infection, host components can also contribute to biofilm matrix.

Biofilm significance:

Clinical significance – they offer protection against immune system and antibiotics, chronic infection. Bacteria in biofilms can be up to 1,000 times more tolerant to antibacterials than the equivalent planktonic bacteria, and contribute to failure of antimicrobial therapy. Tolerance is a transient non-heritable phenotype. Tolerance mechanisms include:

-            Restricted diffusion of antimicrobials through the biofilm matrix

-            Reduced metabolic activity and growth rates

-            Presence of persister cells – effectively dormant cells. Antibiotics target metabolically active bacterial cells – no activity = can’t work/target cells. Metabolically active cells are directed to the periphery of cells.

Many antimicrobial agents can readily diffuse through the biofilm matrix, however slowed diffusion may enable microbes to mount an adaptive response. Diffusion is profoundly influenced by charge interactions with matrix components. Positively-charged aminoglycoside antibiotics can bind matrix components, while negatively-charged B-lactam antibiotics do not.

Industrial significance – biofilm growth within industrial plants and pipelines can impact processes and present contamination risks.

Adherence of bacteria to host cells can also lead to the invasion of host cells, which is often mediated by cytoskeletal rearrangements.

Invasion:

The consequences of invasion can be wide-ranging, and dependent on the specific nature of the host-pathogen interaction, It triggers:

-            The production of proinflammatory cytokines and chemokines, leading to the recruitment of inflammatory cells

-            Epithelial cell apoptosis and subsequent exfoliation – helps clear infection, clearance mechanism

-            Persistence of the bacterium within the host cell

-            Invasion of underlying cells/tissue – e.g. Salmonella typhi

Flagellar-mediated motility:

Flagella are long, thin appendaged attached to the bacterial cell. They function by rotation, pushing or pulling the bacterial cell through the liquid medium. The speed of flagellar rotation varies depending on the strength of the proton motive force. Certain bacteria can sense environmental signals and move away or towards them by altering the direction of flagella rotation.

Chemotaxis, and the ‘biased random walk’:

-            Counter-clockwise flagellar rotation results in the cell swimming forward

-            Clockwise rotation results in the cell stopping and randomly ‘tumbling’

If moving up a gradient of attractant, the runs become longer and tumbles less frequent -> ‘biased random walk’.