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Abstract
Mycoplasma pneumoniae is a common cause of human respiratory tract infections and best known as the etiologic agent of atypical or walking pneumonia. M. pneumoniae binds to glycoprotein receptors having terminal sialic acid residues and glycolipids having sulfate functional groups. In this dissertation, we utilized two in vitro models to explore the impact of terminal sialic acid and sulfate presentation on M. pneumoniae adherence and gliding. We utilized surfaces coated with the sialylated glycoproteins laminin or human chorionic gonadotropin (hCG) or the sulfated glycolipid sulfatide; and chemically functionalized surfaces having -2,3- and -2,6-sialyllactose ligated individually or in combination to a polymer scaffold in precisely controlled densities. Both sialylated and sulfated receptors supported M. pneumoniae adherence, but gliding motility was only present on laminin and -2,3-sialyllactose. The density of sialylated residues influenced M. pneumoniae gliding frequency but not gliding speed, and gliding required a receptor density threshold higher than that needed to support adherence. However, at very high -2,3-sialyllactose densities gliding frequency was actually reduced relative to peak gliding noted at lower receptor densities. Finally, gliding on -2,3-sialyllactose was inhibited on surfaces also conjugated with -2,6-sialyllactose. Thus, both -2,3- and -2,6-sialyllactose may bind P1 adhesin complexes despite the inability of the latter to support gliding. Terminal organelle mutants were also utilized to further elucidate the interaction of M. pneumoniae adhesins and sialylated and sulfated receptors. The absence of functional terminal organelle protein P30, which results in non-functional P1, resulted in loss of attachment to sialylated but not sulfated receptors. Indicating that sulfated receptors may interact with an alternate adhesin than the P1 complex. In summary, the nature and density of host receptor moieties can have a profound influence on M. pneumoniae gliding, which could in turn affect pathogenesis, persistence, and infection outcome.