causes enormous economic losses to swine production worldwide by colonizing the
causes enormous economic losses to swine production worldwide by colonizing the ciliated epithelium in the porcine respiratory tract, resulting in widespread damage to the mucociliary escalator, prolonged inflammation, reduced weight gain, and secondary infections. P146 occurs. Recombinant fragments F1P146-F3P146 that mimic P50P146, P40P146, and P85P146 were constructed and shown to bind porcine epithelial cilia and Duloxetine HCl supplier biotinylated heparin with physiologically relevant affinity. Recombinant versions of F3P146 generated from strain J and 232 sequences strongly bind porcine plasminogen, and the removal of their respective C-terminal lysine and arginine residues significantly reduces this interaction. These data reveal that P146 is an extensively processed, multifunctional adhesin of regulates protein topography. IMPORTANCE Vaccines used to control infection provide only incomplete protection. Protein from the P97/P102 family members are extremely indicated, functionally redundant molecules that are substrates of endoproteases that generate multifunctional adhesin fragments around the cell surface. We show that P146 displays a chimeric structure consisting of an N terminus, which shares sequence identity with P97, and novel central and C-terminal regions. P146 is usually endoproteolytically processed at multiple sites, generating at least nine fragments on the surface of species have evolved strategies to vary their surface topography to avoid detection and eradication by the host immune response (1). Mycoplasmas are the smallest self-replicating life forms with most genomes ranging in size from 500 to 1 1,300?kb. Gene families encoding proteins displayed on the surface with reiterated sequences in their promoter or coding regions are highly mutable due to slip strand mispairing and have been reported in a number of species (2C4). Mutations in these reiterated regions generate phase (on/off) and size variants that contribute to surface diversity and immune evasion. is unusual in this regard with analysis of four complete genome sequences failing to find evidence of reiterated sequences capable of inducing variable expression of most dominant Duloxetine HCl supplier surface proteins (5C7). Despite this, causes porcine enzootic pneumonia, a chronic geographically widespread respiratory disease that inflicts severe economic losses to pig production (8, 9). Within the confines of commercial swine-rearing facilities, enters naive animals via the inhalation of mucorespiratory droplets expelled during bouts of coughing from must overcome the mucociliary Duloxetine HCl supplier escalator and traverse layers of heavily glycosylated mucins produced as decoys for bacterial adhesins that exploit surface glycoconjugates and extracellular matrix components during colonization. is usually highly adept at colonizing ciliated respiratory epithelia (11, 12) where it initially causes ciliostasis but eventually destroys Duloxetine HCl supplier cilia and induces epithelial Duloxetine HCl supplier cell death. Heparin effectively blocks the binding of to porcine cilial preparations (13), indicating that is reliant around the presentation of heparin-binding proteins on its cell surface. Proteoglycans with highly sulfated glycosaminoglycan (GAG) side chains are prominently displayed on the surface of ciliated epithelium lining the porcine respiratory tract (14). Enzootic pneumonia is usually a chronic disease, and adaptive immune responses must be evaded for to survive and proliferate within host tissues. Consequently, the ability to adhere tightly to respiratory cilia is usually a key strategy employed by pathogens to overcome the mucociliary escalator (11, 13, 15, 16). Functional redundancy within key surface protein families is identified in multiple pathogens and may be a strategy to avoid immune responses and regulate both adhesion to host tissues and cellular invasion (17, 18). In is usually indicated by reverse transcription-PCR (RT-PCR) of mRNA recovered from TRA1 the bronchoalveolar lavage (BAL) fluid of experimentally infected swine (30). P97/P102 paralog family members around the cell surface of are targets of endoproteolytic processing events that generate a substantial combinatorial repertoire of cleavage fragments. Fragments of P97, P216, P135, Mhp271, Mhp107, and Mhp108 have been shown to bind porcine cilia (21C,26),.