Staphylococcus Shows Complex Enzyme Redundancy, Study Finds

A Bacterial Pathogen That Refuses to Fail

In a recent study published in mBio, researchers have discovered that Staphylococcus aureus, a notorious pathogen responsible for skin infections and life-threatening systemic illness, demonstrates a remarkable level of metabolic redundancy. This survival trait may partially explain the bacterium’s success in resisting treatment, including in antibiotic-resistant strains like MRSA.

The team focused on a group of bacterial enzymes responsible for producing isoprenoids, molecules essential for respiration, cell wall synthesis, and pigmentation. These functions are critical to bacterial viability, yet when one of the enzymes (IspA) was disrupted, the bacterium continued to thrive. The redundancy in this metabolic pathway, particularly through an alternative enzyme known as HepT, offered new insight into the robust nature of bacterial survival strategies.

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Knockout Mutants Reveal Hidden Survival Pathways

Using knockout mutants, the researchers found that disabling IspA alone was not lethal due to compensatory activity from HepT, highlighting a productive enzyme redundancy in Staph. Only when both genes were knocked out did the bacterial growth and pigmentation cease, confirming the survival dependency on at least one active pathway.

“So, how in the world is a mutation in ispA viable? How can the cell tolerate that? That’s really what started this project off. It was really just a basic science investigation.”

–Troy Burtchett, MGI PhD graduate

This discovery of metabolic redundancy in Staphylococcus aureus sheds light on why treatment strategies often fail, especially in persistent infections. It also helps explain how MRSA adapts rapidly under stress, making conventional antibiotics less effective over time.

As the study was supported by an NIH grant, it holds promise for advancing future clinical research, particularly around novel antibiotic development from pathway inhibition. Targeting both enzyme pathways simultaneously could present a new therapeutic angle against hard-to-treat staph infections.

A New Frontier in Targeting Resistant Pathogens

For healthcare professionals and researchers, this insight opens the door to reevaluating how we approach antibiotic resistance. By focusing on dual-pathway inhibition, drug developers may be able to bypass the adaptive mechanisms that have rendered many antibiotics ineffective against Staphylococcus species.

Clinicians working in infectious diseases, critical care, and microbiology should be aware of this new dimension in bacterial metabolism. Understanding these compensatory mechanisms can help guide more effective antimicrobial strategies and influence future CME/CE content for clinical practice updates.

For More information: 

Burtchett, T. A., et al. (2025). A redundant isoprenoid biosynthetic pathway supports Staphylococcus aureus metabolic versatility. mBio. doi.org/10.1128/mbio.00353-25.