Application of Bacterial Pathogens in Replacement Therapy
John R. Tagg, Jeremy P. Burton and Philip A. Wescombe
As our knowledge of the cellular content and intercellular dynamics of the indigenous microbiota increases, so too does our ability to rationally adjust its composition to heighten its specific pathogen‑excluding capabilities. In replacement therapy the principal objective is to modulate the composition of the indigenous microbiota, in instances where it is considered potentially vulnerable to pathogen overgrowth. This is achieved by supplementing the existing bacterial population with “effector” strains that are equipped to competitively oust or repel members of targeted bacterial species thought to have disease‑causing capability. Often however it proves difficult to lodge new bacterial entities within the existing microflora of the host; finely‑tuned molecular mechanisms intrinsic to the established community typically operate to maintain a population status quo. One attribute of bacteria that may assist their establishment and survival within these complex ecosystems appears to be their production of and/or expression of specific immunity to anti‑competitor peptide antibiotics called bacteriocins. For most bacteria, the strongest niche competitors are probably other bacteria of the same or closely‑related species. Hence, the effector strains chosen for replacement therapy often are either naturally‑occurring or engineered low‑virulence variants of the targeted pathogenic species. In the future it should increasingly prove possible to judiciously engineer effector strains, not only to reduce their virulence, but also to express traits that will enhance their genetic stability, niche competitiveness and physical resilience in the face of the various challenges that confront them both ex vivo and in situ.