Biological hotspots in oceans as unique reservoirs for novel antibiotics

Oceans span over 70% of the Earth’s surface. The wide range of environments coupled with the large diversity of organisms have creatively-shaped unique biological interactions. Antibiotics are forms of natural products synthesized mostly by bacteria to influence or terminate other bacteria, and whose production is stimulated through biological interactions. Antibiotics are best-known for their clinical and agricultural purposes. However, their effectiveness is rapidly diminishing because overuse and misuse has driven a proliferation of resistance and resulted in an emerging crisis of multidrug-resistant (MDR) pathogens. A critical requisite for controlling MDR pathogens is through discovery of new antibiotics having novel mechanisms of action (MOA). Since most present-day antibiotics are derived from a relatively narrow range of soil bacteria isolated decades ago, there has been recent emphasis to isolate novel antibiotics from unique environments among the Earth’s vast microbiome.

Ocean systems offer a strong potential as reservoirs for novel antibiotics. This commentary argues that this will occur primarily in areas of intense biological interactions; where microbes interact either with each other or with plants and animals. Such interactions include animal symbioses; microbe-microbe interactions in hypersaline microbial mats; surface biofilms of marine plants and vertebrate/invertebrate animals; and the internal microbiomes of host animals. Discovery has progressed from screening of cultured bacterial-isolates to a growing arsenal of more-recent approaches: 1) probing metagenomes and transcriptomes; 2) induction of “silent genes”; 3) exploiting ecological relationships of natural bacteria- those not observed under pure-culture conditions; and 4) chemical genomics targeting conserved pathways in bacterial physiology. Given recent advances in sequencing, bioinformatics, and gene manipulation, these capabilities are becoming increasingly feasible. The relatively untapped microbial reservoirs of oceans offer a potentially-limitless source for isolation of novel antibiotics, and whose ecological interactions may be used to advance our fundamental understanding of bacteria.