NATURAL PRODUCTS

Background

 

Natural products are secondary metabolites that are derived from intermediates from primary metabolites. Unlike primary (or central) metabolites, which are involved in vital functions such as growth of an organism, the absence of secondary metabolites does not result in immediate death of an organism. Their functions are ecological in nature, and have a wide range of uses, from protection to mate recognition. In the case of bacteria, secondary metabolites are produced so that they can compete with their neighbouring bacteria (Gorlenko et al. 2020).

 

Many antibiotics that we use today originate from secondary metabolites produced by bacteria that live in the natural world. Half of all antibiotics discovered come from compounds produced by the bacteria Actinomyces. These bacteria are found in a wide range of environments including fresh and saltwater, however the majority are found in soils.

Bioprospecting

 

Due to the rising threat of antibiotic resistance (Chandler, 2019), antibiotic researchers continue to revisit the natural world to look for new compounds that could produce new antibiotics. This exploration is known as bioprospecting.

 

Bacteria that live in very different environments to each other are likely to produce different compounds, which may lead to the development of new antibiotics (Singh et al. 2016). Bioprospecting has therefore extended to the furthest reaches of the world, across many different environments. Some of the more extreme environments where new compounds are searched for include the deep sea and the arctic circle.

Leafcutter ants and protection of their fungal gardens

An example of antibiotic activity produced by secondary metabolites from bacteria is found on leafcutter ants. These ants collect leaf cuttings and grow a fungus (Leucoagaricus gonglyophorous) symbiotically in their fungal gardens. This fungus breaks down the leaves, and in turn the ants digest the edible structures of this fungus. However, there is a parasitic fungus that infect these gardens (Escovopsis) which can threaten the ants’ source of food, and has also been found to produce compounds that manipulate the behaviour of the ants and abandon their gardens (Heine et al., 2018).

 

These leafcutter ants have evolved to defend their fungal gardens chemically with the help of Pseudonocardia, a strain of bacteria found growing on the ants’ cuticles (Worsley et al., 2019). These bacteria produce secondary metabolites that are selectively antifungal and targets the parasitic Escovopsis fungus, protecting the L. gonglyophorous fungus which provides the ants’ source of food (see Figure 1).

 

Furthermore, due to years of collecting many different bacterial strains from wide ranging environments, leafcutter ants also have an abdominal microbiome shaped by their agricultural lifestyle (Sapountzis et al., 2019). Their use of multidrug therapy makes them ideal candidates for investigating potential compounds that may produce antibiotics.

 

Research carried out at the University of East Anglia has resulted in the collection of more than 500 unique bacterial strains from colonies of leafcutter ants. These bacterial strains are being screened for their potential to develop into antibiotics.

Figure 1. Leaf cutter ants, their fungal gardens and their defence mechanism against parasitic fungus (Escovopsis)

References

Chandler C (2019) Current accounts of antimicrobial resistance: stabilisation, individualisation and antibiotics as infrastructure. Palgrave Commun 5: 53. Available at: https://doi.org/10.1057/s41599-019-0263-4.

 

Gorlenko CL, Kiselev HY, Budanova EV, Zamyatnin AA Jr, Ikryannikova LN (2020) Plant Secondary Metabolites in the Battle of Drugs and Drug-Resistant Bacteria: New Heroes or Worse Clones of Antibiotics? Antibiotics (Basel). 9(4):170.

 

Heine D, Holmes NA, Worsley SF, et al (2018) Chemical warfare between leafcutter ant symbionts and a co-evolved pathogen. Nat Commun 9: 2208.

 

Sapountzis P, Nash DR, Schiøtt M, Boomsma JJ (2019) The evolution of abdominal microbiomes in fungus‐growing ants. Mol Ecol. 28: 879– 899.

 

Singh V, Haque S, Singh H, Verma J, Vibha K, Singh R, Jawed A, Tripathi CKM (2016) Isolation, Screening, and Identification of Novel Isolates of Actinomycetes from India for Antimicrobial Applications. Front. Microbiol. 7:1921. 

Worsley S, Hutchings M, Murrell C, (2019) The chemical ecology of protective microbiomes in plant roots and leafcutter ants. Access Microbiology 1.