Pathogens that traffic in the blood of their hosts must employ mechanisms to evade the host innate immune system, including the complement cascade. The Lyme disease spirochete,Borreliella burgdorferi, has evolved numerous outer membrane lipoproteins that interact directly with host proteins. Compared to Lyme disease-associated spirochetes, relatively little is known about how an emerging tick-borne spirochetal pathogen,Borrelia miyamotoi, utilizes surface lipoproteins to interact with a human host.B. burgdorferiexpresses the multifunctional lipoprotein, BBK32, that inhibits the classical pathway of complement through interaction with the initiating protease C1r, and also interacts with fibronectin using a separate intrinsically disordered domain.B. miyamotoiencodes two separatebbk32orthologs denotedfbpAandfbpB; however, the activities of these proteins are unknown. Here, we show thatB. miyamotoiFbpA binds human fibronectin in a manner similar toB. burgdorferiBBK32, whereas FbpB does not. FbpA and FbpB both bind human complement C1r and protect a serum-sensitiveB. burgdorferistrain from complement-mediated killing, but surprisingly, differ in their ability to recognize activated C1r versus zymogen states of C1r. To better understand the observed differences in C1r recognition and inhibition properties, high-resolution X-ray crystallography structures were solved of the C1r-binding regions ofB. miyamotoiFbpA and FbpB at 1.9Å and 2.1Å, respectively. Collectively, these data suggest that FbpA and FbpB have partially overlapping functions but are functionally and structurally distinct. The data presented herein enhances our overall understanding of how bloodborne pathogens interact with fibronectin and modulate the complement system.

Adult brook trout (Salvelinus fontinalis) were exposed for up to 11 d to one of a matrix of 18 Al, low pH, and Ca2+ combinations, chosen as representive of acidified softwater environments in the wild. Reduction in water pH led to pH-dependent net losses of Na+ and Cl− exacerbated by the presence of Al in the water and reduced by elevating Ca2+. Any animal losing more than 4% of its total body Na+ over the first 24 h of Al exposure had a greater than 90% likelihood of eventual mortality. Na+ losses arose from inhibition of influx and stimulation of efflux. The inhibition was persistent and pH dependent. Addition of Al to acidified water had a slight further inhibitory effect on Na+ influx and a large stimulatory effect on efflux. The latter was dependent on Al concentration, was the main cause of initial ion losses and mortality, and declined with time in surviving animals. All Al-exposed fish accumulated Al on their gills, but this was apparently mainly surface or subsurface bound, since no internal Al (plasma or liver) could be detected. Nonsurviving fish had substantially higher gill Al levels than survivors.

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