GEN Exclusives

More »

GEN News Highlights

More »
Feb 21, 2014

Bacterial Resistance Mechanism Exposed: New Antibiotics May Follow

  • Scientists from the Florida campus of the Scripps Research Institute (TSRI) have shed light on a novel mechanism of drug resistance. This knowledge could have a major impact on the development of a pair of highly potent new antibiotic drug candidates, the researchers say.

    “Now, because we know the resistance mechanism, we can design elements to minimize the emergence of resistance as these promising new drug candidates are developed,” said Ben Shen, Ph.D., a TSRI professor who led the study (“Mechanisms of Self-Resistance in the Platensimycin- and Platencin-Producing Streptomyces platensis MA7327 and MA7339 Strains”), which is published online ahead of print in Chemistry & Biology.

    The study centers around Streptomyces platensis, which protects itself from other bacteria by secreting antibacterial substances. Interestingly, S. platensis belongs to a large family of antibiotic-producing bacteria that accounts for more than two-thirds of naturally occurring clinically useful antibiotics.

    The antibiotic compounds secreted by S. platensis, which are called platensimycin (PTM) and platencin (PTN) and were discovered only recently, work by interfering with fatty acid synthesis, which is essential for the production of bacterial cell walls and, consequently, the bacteria's existence. Platencin, although structurally similar to platensimycin, inhibits two separate enzymes in fatty acid synthesis instead of one.

    The question remained, though, of why these compounds killed other bacteria, but not the producing bacteria S. platensis.

    “Knowing how these bacteria protect themselves, what the mechanisms of self-resistance of the bacteria are, is important because they could transfer that resistance to other bacteria,” said Tingting Huang, Ph.D., a research associate in the Shen laboratory who was first author of the study with Ryan M. Peterson, Ph.D., of the University of Wisconsin-Madison.

    Using genetic and bioinformatic techniques, the team identified two complementary mechanisms in the bacteria that confer resistance to platensimycin and platencin. In essence, the study found a pair of genes in S. platensis exploits a pathway to radically simplify fatty acid biosynthesis while bestowing an insensitivity to these particular antibiotics.

    “We now identify two mechanisms for PTM and PTN resistance in the S. platensis producers—the PtmP3 or PtnP3 gene within the PTM-PTN or PTN biosynthetic cluster and the FabF gene within the fatty acid synthase locus,” wrote the investigators. “PtmP3/PtnP3 and FabF confer PTM and PTN resistance by target replacement and target modification, respectively. PtmP3/PtnP3 also represents an unprecedented mechanism for fatty acid biosynthesis in which FabH and FabF are functionally replaced by a single condensing enzyme. These findings challenge the current paradigm for fatty acid biosynthesis and should be considered in future development of effective therapeutics targeting fatty acid synthase.”

    “Understanding how these elements work is a big leap forward,” noted Jeffrey D. Rudolf, Ph.D., a research associate in the Shen lab who worked on the study. “Now these bacteria have shown us how other bacteria might use this resistance mechanism to bypass fatty acid biosynthesis inhibition.”

Related content


GEN Jobs powered by connects you directly to employers in pharma, biotech, and the life sciences. View 40 to 50 fresh job postings daily or search for employment opportunities including those in R&D, clinical research, QA/QC, biomanufacturing, and regulatory affairs.
More »

Be sure to take the GEN Poll

The Triple Package and Success

One theory for explaining “success," put forward by Amy Chua Jed Rubenfeld, posits cultural traits such as a superiority complex, personal insecurity and impulse control. Union College professors Joshua Hart and Christopher Chabris counter that intelligence, conscientiousness, and economic advantage are the most likely elements of success, regardless of ethnicity. Do you think that Hart-Chabris make a better argument for achieving success than the Chua-Rubenfeld theory?

More »