Chapter 114. Molecular Mechanisms
of Microbial Pathogenesis
(Part 3)

Viral Adhesins
(See also Chap. 161) All viral pathogens must bind to host cells, enter
them, and replicate within them. Viral coat proteins serve as the ligands for
cellular entry, and more than one ligand-receptor interaction may be needed; for
example, HIV uses its envelope glycoprotein (gp) 120 to enter host cells by
binding to both CD4 and one of two receptors for chemokines (designated CCR5
and CXCR4). Similarly, the measles virus H glycoprotein binds to both CD46 and
the membrane-organizing protein moesin on host cells. The gB and gC proteins on
herpes simplex virus bind to heparan sulfate; this adherence is not essential for
entry but rather serves to concentrate virions close to the cell surface. This step is
followed by attachment to mammalian cells mediated by the viral gD protein.
Herpes simplex virus can use a number of eukaryotic cell surface receptors for
entry, including the herpesvirus entry mediator (related to the tumor necrosis
factor receptor); members of the immunoglobulin superfamily; two proteins called
nectin-1 and nectin-2; and modified heparan sulfate.

Bacterial Adhesins

Among the microbial adhesins studied in greatest detail are bacterial pili
and flagella (Fig. 114-1). Pili or fimbriae are commonly used by gram-negative
and gram-positive bacteria for attachment to host cells and tissues. In electron
micrographs, these hairlike projections (up to several hundred per cell) may be
confined to one end of the organism (polar pili) or distributed more evenly over
the surface. An individual cell may have pili with a variety of functions. Most pili
are made up of a major pilin protein subunit (molecular weight, 17,000–30,000)
that polymerizes to form the pilus. Many strains of Escherichia coli isolated from
urinary tract infections express mannose-binding type 1 pili, whose binding to the

Moraxella spp., Vibrio cholerae, Legionella pneumophila, Salmonella enterica
serovar typhi, enteropathogenic E. coli, and Pseudomonas aeruginosa, mediates
adherence of these organisms to target surfaces. These pili tend to have a relatively
conserved amino-terminal region and a more variable carboxyl-terminal region.
For some species (e.g., N. gonorrhoeae, Neisseria meningitidis, and
enteropathogenic E. coli), the pili are critical for attachment to mucosal epithelial
cells. For others, such as P. aeruginosa, the pili only partially mediate the cells'
adherence to host tissues. Whereas interference with this stage of colonization
would appear to be an effective antibacterial strategy, attempts to develop pilus-
based vaccines for human diseases have not been highly successful to date.