Bacterial vampirism mediated through taxis to serum

Abstract

Severe bacterial infections of the gastrointestinal (GI) tract instigate GI hemorrhaging that can lead to bacteremia, sepsis, and death. Pathogens preferentially colonize sites of injury, delaying healing and exacerbating tissue damage, but the underlying mechanisms are not well understood. We find that Enterobacteriaceae species are remarkably sensitive to human serum and perceive femtoliter quantities as a potent attractant. This behavior is driven by chemotaxis and the Tsr chemoreceptor, which recognizes L-serine present in serum. By studying the crystal structure of Salmonella Typhimurium Tsr, we identified a recognition motif for L-serine and found similar Tsr homologues in various Enterobacteriaceae species, including World Health Organization priority pathogens. Our analyses of Escherichia and Citrobacter bacteria, which also possess Tsr, confirm that these species exhibit chemoattraction to serum. We have coined the term 'vampirism' to describe this pathogenesis strategy and suggest it plays a role in injury tropism and increases the risk of bacteremia.

Navigating contradictions: Salmonella Typhimurium chemotactic responses to conflicting chemoeffector signals show parity with bacterial growth benefits

“…3H), and found that the tsr mutant is unable to respond to either effector. Since our earlier work demonstrated that the tsr strain retains chemotaxis to other stimuli 9 we conclude that Tsr is responsible for indole chemorepulsion.…”

“…In this assay, a constant flow of approximately 300 femtoliters per minute is applied to inject the effector through a glass microcapillary 0.5 µm in diameter; chemoattraction is observed as an influx of cells into the field of view over time and congregation near the source, and chemorepulsion is observed as decreasing cells over time and avoidance of the central effector source (Fig. 1C-E) 9 .…”

“…CIRA was performed as described previously 9 . Briefly, an Eppendorf Femtotip 2 microcapillary containing the treatment of interest was lowered into a pond of 50 µl of motile cells using a Sutter micromanipulator.…”

“…The chemotaxis systems of many host-associated bacteria, both native commensal and pathogenic species, have been shown to be important for colonization and survival within the host gut 1,4 . Chemotaxis enables motile bacteria to rapidly relocate based on novel sources of effector stimuli and to exert precise control of colonization at the micron-level scale [9][10][11][12] . These abilities translate into growth advantages during initial and long-term colonization because they allow bacteria to adapt to the dynamic circumstances within the gut, which changes frequently in terms of nutrient content, fluidic flow, and microbial competition 1,13,14 .…”

“…One example is the chemoreceptor taxis to serine and repellents (Tsr), which we have shown to be widely distributed among bacterial colonizers of the gut, especially Enterobacteriaceae (Fig. 1A) 1,9 .…”