Engineering commensal bacteria for prophylaxis against infection

Abstract

Infectious diseases are the leading causes of death worldwide. The development of efficient and low cost prophylactics to prevent pathogenic infection is given high priority in the twenty-first century. Commensal bacteria are largely seen as harmless and can survive symbiotically (in many cases) in niches throughout the human body. Advances in genetic engineering and understanding of pathogenesis have revealed many potential strategies to develop engineered bacteria for prophylaxis purposes: including live vaccines and anti-infective agents. In this review, we discuss recent advances and potentialities of prophylaxis with engineered bacteria.

Figure 1

Body sights sampled by the Human Microbiome Project. Engineered commensal bacteria are typically targeted to the respiratory system, gastrointestinal tract and urogenital tract (yellow box).

Figure 2

(A) Schematic diagram of how commensal bacteria can be used to speed up infection cycles of V.cholerae. At low cell density, V.cholerae secrete cholera toxin (CT) and toxin coregulated pilus (TCP), which facilitate host ionic imbalance and V. cholerae attachment to host epithelia (red cells), respectively. At high cell density, high concentration of cholerae autoinducer-1 (CAI-1) and autoinducer-2 (AI-2) are present within the colonization site. The virulence genes are turned off by the QS circuit and VC discontinue expressing CT and TCP. V. cholerae detaches and leaves the infected host through the massive efflux of fluid. (B) Engineered commensal bacteria can serve as a prophylactic against cholera by expressing the V. cholerae autoinducers. Excess CAI-1 and AI-2 imitate the high cell density scenario and signal invading V. cholerae to leave the gut before causing damage to the host cells.