Notes
Bacterial Pathogenesis: Colonization
Sections
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.
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.
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.
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Images:
Diphtheria (H Gaspar, Andrew & Ton-That, Hung. (2006). Assembly of Distinct Pilus Structures on the Surface of Corynebacterium diphtheriae. Journal of bacteriology. 188. 1526-33. 10.1128/JB.188.4.1526-1533.2006.)
Dental plaque biofilm (Wikipedia; Ajeverette)
E. coli pili (Manu Forero; http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040314)
Type III Secretion System (Wikipedia; Cropped image from Schraidt et al. (2010), Topology and Organization of the Salmonella typhimurium Type III Secretion Needle Complex Components. PLoS Pathog 6(4): e1000824. doi:10.1371/journal.ppat.1000824)
Heart Valve (Special thanks to Jamie Donnelly, M.D.).
Neisseria gonorrhoeae (NIH newsroom; https://www.nibib.nih.gov/news-events/newsroom/infectious-disease-vaccines-get-boost-imaging-program)
Spa Pili (Andrew H. Gaspar, and Hung Ton-That J. Bacteriol. 2006;188:1526-1533)
GAS pili (Marirosa Mora, Giuliano Bensi, Sabrina Capo, Fabiana Falugi, Chiara Zingaretti, Andrea G. O. Manetti, Tiziana Maggi, Anna Rita Taddei, Guido Grandi, John L. Telford. (2005). Group A Streptococcus produce pilus-like structures containing protective antigens and Lancefield T antigens. Proceedings of the National Academy of Sciences Oct 2005, 102 (43) 15641-15646; DOI: 10.1073/pnas.0507808102).
GBS pili (Rosini Roberto, Margarit Immaculada (2015). Biofilm formation by Streptococcus agalactiae: influence of environmental conditions and implicated virulence factors. Frontiers in Cellular and Infection Microbiology. DOI=10.3389/fcimb.2015.00006.