Harnessing the Power of Defensive Microbes: Evolutionary Implications in Nature and Disease Control

Microbes are vital to the functioning of multicellular organisms. This realisation has fuelled great interest in the effects of microbes on the health of plant [1–3] and animal hosts [4–6] and has revealed that microbe-mediated protection against infectious disease is a widespread phenomenon (Table 1) [7–11]. Defensive microbes can protect hosts from infection by parasites (including pathogens and parasitoids) by direct or host-mediated means (Box 1). Such protective traits have made these microbes attractive candidates for disease control. In fact, defensive microbes are already being applied in phage therapy and bacteriotherapy for humans, as well as to control vector-borne and agricultural diseases (Table 2).Box 1. Mechanisms of Defensive MicrobesDirectHyperparasitism or predation: Microbes can parasitise or predate upon the parasite [39].Interference competition: Microbes can produce toxic compounds, such as antibiotics or bacteriocins, that may either kill the parasite or reduce its growth rate [40–42].Resource competition: Microbes can compete with parasites for host resources [10,42], usually via the rate of resource acquisition [40,41].Host-mediatedHost immune-mediation: Microbes can elicit a host immune response to which the parasite is not resistant [40,42].Host tolerance-mediation: Microbes can increase the fitness of their host during infection without reducing the fitness of the parasite by enhancing host tolerance (e.g., via tissue damage prevention and/or repair) [43,44].Table 1Defensive microbes in nature.Table 2Applications of defensive microbes in infectious disease control.Despite the impact defensive microbes can have on host and parasite fitness, our current perspective of host–parasite evolution is largely based upon pairwise species interactions [12]. By combining knowledge of defensive microbe–parasite interactions at the mechanistic level with evolutionary theory, we can predict how defensive microbes might alter the evolution of host and parasite traits, such as resistance and virulence. This will not only shape how we understand patterns of host–parasite coevolution in nature but will inform our decisisons in utilising defensive microbes as disease control agents. We propose three potential evolutionary implications of defensive microbes on host–parasite interactions.