23.4.1 Novel Antimicrobial Compounds
With the rapid emergence of drug-resistant pathogens, there has been a renewed
effort to search for novel antimicrobials in the environment. In the past, antimicrobials were isolated from soil samples, however, frequent re-discovery of the same
compounds has encouraged scientists to explore other niches for new antimicrobials.
Increasingly, it is thought that defensive microbiomes may yield structurally diverse
and novel compounds that have a greater efficacy against human pathogens (Adnani
et al. 2017; Chevrette et al. 2019; Seipke et al. 2012). Within the microbiome,
microbial species face intense competition for host resources. This fuels the production of antimicrobial agents as species produce them to inhibit the growth of
competing microorganisms. Symbiotic species that rely on their host for resources
must also ensure continued host survival. Thus, coevolutionary dynamics between
invading pathogens, symbionts and host organisms, are expected to result in the
continued evolution of novel antimicrobial compounds with distinct activities. These
may be able to target pathogen populations that are clinically relevant (Pathak et al.
2019; Adnani et al. 2017; Chevrette et al. 2019). For example, a group of compounds
called the formicamycins have recently been isolated from a species of Streptomyces
growing in association with African tetraponera plant-ants; these compounds were
shown to inhibit multidrug resistant pathogens which showed no evidence of being
able to evolve resistance, suggesting that the formicamycins had a highly effective
mode of action (Qin et al. 2017). Looking within microbiomes for new antimicrobials may also prove advantageous, since compounds produced by beneficial
microbes that interact with a eukaryotic host are likely to prove less toxic to
human cells, or those of other animal and crop species (Adnani et al. 2017).
23.4.2 Safeguarding Our Antimicrobials
There is evidence to suggest that several defensive mutualisms have remained
effective for millions of years, with little evidence of pathogenic resistance evolving
in these systems. For example, Beewolf digger wasps are thought to have been using
the same antibiotics (produced by their Streptomyces symbionts) since the Cretaceous period (Engl et al. 2018). It is thought that pathogen resistance is avoided in
this system because the Streptomyces symbionts produce a large variety of antimicrobials at any one time. In fact, it has been shown that multiple antimicrobials, that
vary slightly in their structure and activity, can be produced from the same gene in
the Streptomyces symbiont’s genome (Engl et al. 2018). This variable cocktail, in
addition to the targeted application of antibiotics in the larval brood chamber, is
thought to reduce the chances of pathogen resistance evolving, as multiple cellular
processes are targeted at once. Such multidrug strategies are thought to be common
across vertebrate and invertebrate species (Florez et al. 2015). Leafcutter ants are
also known to use multidrug therapy to combat infections in their fungal gardens;
23 Defensive Microbiomes: A Widespread Phenomenon in Nature
505
With the rapid emergence of drug-resistant pathogens, there has been a renewed
effort to search for novel antimicrobials in the environment. In the past, antimicrobials were isolated from soil samples, however, frequent re-discovery of the same
compounds has encouraged scientists to explore other niches for new antimicrobials.
Increasingly, it is thought that defensive microbiomes may yield structurally diverse
and novel compounds that have a greater efficacy against human pathogens (Adnani
et al. 2017; Chevrette et al. 2019; Seipke et al. 2012). Within the microbiome,
microbial species face intense competition for host resources. This fuels the production of antimicrobial agents as species produce them to inhibit the growth of
competing microorganisms. Symbiotic species that rely on their host for resources
must also ensure continued host survival. Thus, coevolutionary dynamics between
invading pathogens, symbionts and host organisms, are expected to result in the
continued evolution of novel antimicrobial compounds with distinct activities. These
may be able to target pathogen populations that are clinically relevant (Pathak et al.
2019; Adnani et al. 2017; Chevrette et al. 2019). For example, a group of compounds
called the formicamycins have recently been isolated from a species of Streptomyces
growing in association with African tetraponera plant-ants; these compounds were
shown to inhibit multidrug resistant pathogens which showed no evidence of being
able to evolve resistance, suggesting that the formicamycins had a highly effective
mode of action (Qin et al. 2017). Looking within microbiomes for new antimicrobials may also prove advantageous, since compounds produced by beneficial
microbes that interact with a eukaryotic host are likely to prove less toxic to
human cells, or those of other animal and crop species (Adnani et al. 2017).
23.4.2 Safeguarding Our Antimicrobials
There is evidence to suggest that several defensive mutualisms have remained
effective for millions of years, with little evidence of pathogenic resistance evolving
in these systems. For example, Beewolf digger wasps are thought to have been using
the same antibiotics (produced by their Streptomyces symbionts) since the Cretaceous period (Engl et al. 2018). It is thought that pathogen resistance is avoided in
this system because the Streptomyces symbionts produce a large variety of antimicrobials at any one time. In fact, it has been shown that multiple antimicrobials, that
vary slightly in their structure and activity, can be produced from the same gene in
the Streptomyces symbiont’s genome (Engl et al. 2018). This variable cocktail, in
addition to the targeted application of antibiotics in the larval brood chamber, is
thought to reduce the chances of pathogen resistance evolving, as multiple cellular
processes are targeted at once. Such multidrug strategies are thought to be common
across vertebrate and invertebrate species (Florez et al. 2015). Leafcutter ants are
also known to use multidrug therapy to combat infections in their fungal gardens;
23 Defensive Microbiomes: A Widespread Phenomenon in Nature
505