Antibiotic resistance is a rampant problem around the world. More than 23,000 deaths a year in the US are a result of antibiotic resistant bacteria. Bacteria become resistant to antibiotics in several ways. The antibiotic itself can be broken down, or the components of bacteria targeted by antibiotics can mutate. Over prescription leads to the development of further resistance. With each year there are increasing numbers of bacteria that can’t be killed by our last line of defense (carbapenems). It’s very clear that we are close to the end of an era of effective antibiotics. Discovery of novel antibiotics has waned since the 1960’s and finding new ones is a global health concern that needs attention.

Luckily, researchers are heeding the call and figuring out ways to find new antibiotics. Recently, a group at Rockefeller University has developed a technique to discover antibiotics from soil. The Rockefeller team built on the success of a lab from Northeastern University, that had developed a method to culture bacteria from soil ( iChip) in 2015, and discovered teixobactin, a novel antibiotic. These new techniques have unlocked a previously untapped source for antibiotic discovery. Soil samples have a rich diversity of bacteria that have been historically difficult to work with in the lab. This method overcomes the difficulty of working in a lab by directly sequencing everything in the soil, in order to identify genomic features of interest. The Rockefeller team used this method on 2,000 soil samples, and identified a new set of genes that can create a novel antibiotic, Malacidin. Malacidin was shown to be broadly effective against gram positive bacteria including MRSA.

Brandon Sit, a graduate student studying microbiology at Harvard Medical School, says “Overall while the malicidins may be therapeutically useful, they are very far from the clinic right now. The most impactful part of the paper is its description of the soil analysis pipeline that can be leveraged to bypass any culturing of candidate bacterial to isolate new compounds.” This method will enable scientists to find more genetic pathways that make new antibiotics. This work could be one of the steps in a long staircase that will give us leverage in our never-ending arms race with bacteria.

Acknowledgements: Many thanks to Brandon Sit, a PhD student in the BBS program at Harvard.
Managing Correspondent: Aaron Aker
Original article: Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens
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