OVERVIEW

• The host provides shelter, warmth, moisture, and food for bacteria; as we learn elsewhere, there are several microorganisms that take advantage of these benefits without harming the host – these commensals comprise the microbiome.
• Virulence factors increase a bacterial strain’s ability to colonize and cause disease.
  – The genes for virulence factors are often clustered together in pathogenicity islands; thus, they are easily transferred via plasmids, bacteriophages, and other gene-sharing mechanisms.
  – Furthermore, the genes for many virulence factors are regulated via quorum sensing; as we learn elsewhere, quorum sensing allows for bacterial behaviors to change with group density.

ADHESION TO HOST CELLS & ECM

This early step in colonization unleashes specific pathogen behaviors and host responses.

• Adhesins are molecules that facilitate adhesion to other pathogens or host structures; indicate that they can be located on the tips of pili or on the bacterial cell surface.
• A bacterium can have one or several types of pili and surface adhesions.
  – Different strains of the same bacteria can have different pili types, which can influence their virulence in different host environments.

Gram-Negative bacteria:

• P pili, Type I pili, Curli pili, and Type IV pili.
  – Uropathogenic strains of Escherichia coli use both P pili and Type I pili to adhere to the urothelium of the urinary tract; without these pili, the bacteria would be physically removed by the flow of urine.
  – Some strains of E. coli have curli pili, which, in addition to adhesion, provoke the host inflammatory response.
  – Type IV pili confer twitching motility to some species, independent of flagella; Neisseria gonorrhoeae and Pseudomonas aeruginosa are examples of bacteria that “walk” via retraction of Type IV pili.

Gram-Positive bacteria

• Also have pili-like structures; though assembled differently the pili of Gram-negative bacteria, they perform similar functions.
• Spa, GAS M1, PI-1, PI-2
  – Spa pili, which are long and flexible, facilitate adherence of Corynebacterium diphtheriae, the causative agent of diphtheria, to epithelial cells of the pharynx.
  – Similarly, GAS M1 facilitates adherence of Group A Streptococcus (aka, Streptococcus pyogenes) to pharyngeal epithelial cells.
  – PI-1 and PI-2 facilitate adherence of Group B Streptococcus (Streptococcus agalactiae) to the cells of the lungs.
  PI = Pilus Island, which refers to the gene loci. Group B streptococcus causes neonatal sepsis, pneumonia, and meningitis.

MSCRAMMs

Non-pilus adhesins on the bacterial cell surface that attach pathogens to host structures.

• MSCRAMMs – Microbial Surface Components Recognizing Adhesive Matrix Molecules – are proteins that facilitate colonization by Gram positive bacteria.
• Staphylococcus aureus adheres to fibrinogen via Clumping factor A, and to fibronectin via Fibronectin Binding Protein (FnBP).
• In turn, these ECM components make their own connections to platelets and host cells, thereby establishing secure associations between S. aureus and the host.
• Furthermore, S. aureus can take advantage these associations and enter host cells to either lie latent or act as a super-antigen (for more, see our tutorial on bacterial endocarditis).

Biofilm

• To further secure adherence to the host, and to protect themselves from the immune system and antibiotics, pili and surface adhesins contribute to the formation of biofilms.
• Comprises bacterial cells, in some cases of multiple strains or species, surrounded by matrix. Biofilm formation is an example of a virulence factor regulated by quorum sensing.
  – Dental plaque is an example of a biofilm, which we can see in the image as purple-stained areas.
  – Biofilm production by S. aureus in endocarditis facilitates the growth of large bacterial vegetations, which can damage the heart or, if they break free, cause stroke.

ENTRY INTO HOST CELLS

2 examples of how some bacteria enter into host cells.

Complement Opsonization

• Mycobacterium tuberculosis, the causative of tuberculosis, makes use of complement opsonization.
• Recall that opsonization by C3b typically results in phagocytosis and microbe destruction; however, M. tuberculosis, once taken up by macrophages, avoids destruction and instead replicates inside the host cell.
• Ultimately, pathogen-host interactions result in the formation of granulomas, aka, tubercles, which harbor M. tuberculosis.

Type III secretion system

• The Type III secretion system uses a needle-like structure to inject effectors into host cells.
  – The effectors and their actions vary by bacterial strain.
• In the case of salmonella, the effectors trigger cytoskeleton reorganization of host cells such that the pathogen can enter it; once inside, the bacteria can make use of host cell machinery and replicate.

EVASION OF HOST IMMUNE SYSTEM

Mechanisms to evade phagocytosis

• The polysaccharide capsule on Gram positive bacteria inhibits phagocyte adhesion.
  – Thus, anticapsular antibodies are important preventative measures against infection by Streptococcus pneumoniae and Neisseria meningitides.
• The M protein of Group A Streptococcus (aka, Streptococcus pyogenes) resists opsonization and phagocytosis.
• Protein A, found in the cell wall of Staphylococcus aureus, binds immunoglobulins M and G, preventing complement activation and, therefore, phagocytosis.
• Leukocidins, which are pore-forming cytotoxins released by staphylococcus bacteria, kill leukocytes, including phagocytic neutrophils and macrophages.

Immunoglobin A protease degrades IgA

• This allows the causative agents of bacterial meningitis, Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, to adhere to mucous membranes.