DnaK from Bifidobacterium animalis subsp. lactis is a surface-exposed human plasminogen receptor upregulated in response to bile salts

Abstract

Bifidobacterium animalis subsp. lactis lives in the gastrointestinal tract of most mammals, including humans. Recently, for the probiotic strain B. animalis subsp. lactis BI07, a dose-dependent plasminogen-binding activity was demonstrated and five putative plasminogen-binding proteins were identified. Here we investigated the role of surface DnaK as a B. animalis subsp. lactis BI07 plasminogen receptor. DnaK was visualized on the bacterial cell surface by transmission electron microscopy. The His-tagged recombinant DnaK protein showed a high affinity for human plasminogen, with an equilibrium dissociation constant in the nanomolar range. The capability to tolerate physiological concentrations of bile salts is a crucial feature for an intestinal symbiont micro-organism. By proteome analysis we demonstrated that the long-term exposure of B. animalis subsp. lactis BI07 to bile salts results in the upregulation of important surface plasminogen receptors such as DnaK and enolase. Moreover, adaptation of B. animalis subsp. lactis BI07 to physiological concentrations of bile salts significantly increased its capacity to interact with the host plasminogen system. By enhancing the bacterial capacity to interact with the host plasminogen, the gut bile environment may facilitate the colonization of the human host by B. animalis subsp. lactis BI07.

BBA70 of Borrelia burgdorferi Is a Novel Plasminogen-binding Protein

“…The binding constant for BBA70 lies in a similar range of affinities reported for other plasminogen-binding proteins, such as B. burgdorferi enolase with a K d of 125 nM (34), staphylokinase from S. aureus with a reported K d of 9.3 nM (9), and DnaK and enolase from Bifidobacterium animalis with K d values of 11 and 42 nM, respectively (73,74).…”

Bacterial Virulence in the Moonlight: Multitasking Bacterial Moonlighting Proteins Are Virulence Determinants in Infectious Disease

“…This was followed by the report that cell surface DnaK in M. tuberculosis bound to plasminogen (195 report has established that the Hsp70 protein, DnaK, of Bifidobacterium animalis subsp. lactis is a cell surface receptor for plasminogen whose expression on the surface is upregulated in the presence of bile salts (35). As has been described previously (74), a number of host cell surface molecular chaperones can act as receptors for both bacteria and viruses.…”

Cell surface proteins play an important role in probiotic activities of Lactobacillus reuteri

“…It has been proposed that cell surface proteins are involved in cell protection and surface recognition and that they could be potential mediators in the initial steps involved in autoaggregation and adhesion [8][9][10]. In cell envelope proteome studies of potentially probiotic bacteria, the cell wall protein fraction has typically been extracted by lysozyme-containing buffer [11][12][13][14][15][16], lithium chloride [16,17], or some other cell surface molecule or proteinsolubilizing agent [15][16][17][18].…”