Surreal illustration combining DNA, protein structures, and Burkholderia bacteria, symbolizing scientific discovery and progress against infection.

Decoding Burkholderia: How Genomics Could Lead to New Weapons Against Deadly Infections

Jordan Keane in Health & Wellness June 2025 • 5 min read.

"Scientists are using functional and structural genomics to map the essential components of Burkholderia, paving the way for targeted drug development."

Burkholderia, a group of bacteria, poses a significant threat to human health, causing diseases like melioidosis, glanders, and severe pulmonary infections, especially in those with cancer or cystic fibrosis. What makes these infections particularly alarming is the increasing drug resistance, highlighting the urgent need for new and effective treatments. The race is on to find innovative ways to combat these resilient bacteria.

Traditional approaches to discovering new antimicrobials often involve structure-based drug design and phenotypic screens, both of which require a detailed understanding of the bacteria's essential proteins. High-resolution structures of these proteins are crucial for designing drugs that can precisely target and disrupt the bacteria's functions, ultimately leading to their demise.

Now, a team of scientists is pioneering a new approach: combining functional and structural genomics to map the essential components of Burkholderia. By identifying the genes critical for the bacteria's survival and determining the 3D structures of the corresponding proteins, they hope to create a powerful toolkit for developing the next generation of antibiotics. This article explores how this research is unlocking new possibilities for fighting these deadly infections.

Unlocking Burkholderia's Secrets: A Combined Genomics Approach

Surreal illustration combining DNA, protein structures, and Burkholderia bacteria, symbolizing scientific discovery and progress against infection.

The research team started by experimentally identifying 406 genes in B. thailandensis--a less harmful relative of more dangerous Burkholderia species--that are likely essential for survival. This involved a technique called saturation-level transposon mutagenesis and next-generation sequencing (Tn-seq). In simple terms, they disrupted genes at random and then identified which disruptions were lethal to the bacteria. Those lethal genes are key.

Next, the scientists focused on determining the 3D structures of the proteins produced by these essential genes. However, many proteins are difficult to work with in the lab. To overcome this, they used an "ortholog rescue" strategy.

Ortholog Rescue: They looked for similar genes (orthologs) in other Burkholderia species. The idea is that slight variations in these related proteins might make them easier to study, while still providing useful structural information for drug design.
Structural Coverage: This approach allowed them to obtain structures for 31 proteins from B. thailandensis and 25 orthologs from other species, covering 49 of the 406 essential gene families. In total, 88 structures were deposited into the Protein Data Bank, a public repository for structural data.
Drug Target Analysis: The team then analyzed these protein structures for characteristics that would make them good drug targets, such as having no close human counterpart, being part of an essential metabolic pathway, and possessing a deep binding pocket where a drug molecule could attach. They identified 25 proteins meeting all these criteria.

Ultimately, this comprehensive structural and functional data provides a rich resource for the development of drugs against Burkholderia infections.

Why This Research Matters: A New Era in Antibiotic Discovery?

This research marks a significant step forward in the fight against Burkholderia infections. By combining functional genomics to identify essential genes with structural genomics to visualize the corresponding proteins, scientists have created a powerful platform for drug discovery. The "ortholog rescue" strategy offers a clever workaround to the challenges of protein structure determination, maximizing the potential for finding new drug targets.

The identification of 25 proteins with desirable drug target characteristics is particularly promising. These proteins represent potential Achilles' heels in Burkholderia, offering opportunities to develop highly targeted antibiotics with reduced risk of side effects. The availability of detailed structural information will accelerate the drug design process, allowing researchers to create molecules that precisely fit into the protein's binding pockets and disrupt its function.

While further research is needed to validate these targets and develop effective drugs, this study provides a valuable foundation for future efforts. As antibiotic resistance continues to rise, innovative approaches like this are essential for staying ahead of deadly bacterial infections and protecting public health.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1371/journal.pone.0053851, Alternate LINK

Title: Combining Functional And Structural Genomics To Sample The Essential Burkholderia Structome

Subject: Multidisciplinary

Journal: PLoS ONE

Publisher: Public Library of Science (PLoS)

Authors: Loren Baugh, Larry A. Gallagher, Rapatbhorn Patrapuvich, Matthew C. Clifton, Anna S. Gardberg, Thomas E. Edwards, Brianna Armour, Darren W. Begley, Shellie H. Dieterich, David M. Dranow, Jan Abendroth, James W. Fairman, David Fox, Bart L. Staker, Isabelle Phan, Angela Gillespie, Ryan Choi, Steve Nakazawa-Hewitt, Mary Trang Nguyen, Alberto Napuli, Lynn Barrett, Garry W. Buchko, Robin Stacy, Peter J. Myler, Lance J. Stewart, Colin Manoil, Wesley C. Van Voorhis

Published: 2013-01-31

Everything You Need To Know

What is the main focus of the research, and why is it important?

The research focuses on understanding the bacteria genus *Burkholderia*, which causes severe illnesses like melioidosis and pulmonary infections. The significance lies in the increasing drug resistance of these bacteria, creating an urgent need for new treatments. The implications of not finding new antibiotics are severe, potentially leading to untreatable infections and increased mortality rates, particularly in vulnerable populations like those with cancer or cystic fibrosis. The article highlights the use of functional and structural genomics as a method to combat these illnesses.

How do scientists use functional and structural genomics in this research?

Functional genomics is used to identify the genes essential for *Burkholderia*'s survival. This involves techniques like saturation-level transposon mutagenesis and next-generation sequencing (Tn-seq), where genes are disrupted to determine which are critical for the bacteria's survival. Structural genomics is then used to determine the 3D structures of the proteins produced by these essential genes. Understanding the functions of essential genes and the structures of their corresponding proteins is key. This combined approach allows scientists to identify potential drug targets and understand how to disrupt the bacteria's functions.

What is the "ortholog rescue" strategy?

The "ortholog rescue" strategy is a method used when studying the structures of proteins from *Burkholderia*. Some proteins are challenging to work with in the lab, so the scientists look for similar genes (orthologs) in other *Burkholderia* species. The idea is that these related proteins might be easier to study while still providing useful information for drug design. By obtaining the structures of these orthologs, scientists gain insights that help them understand and target the essential components of *Burkholderia*, enabling the design of new antibiotics.

What makes a protein a good drug target, according to this research?

The researchers identified 25 proteins that are good drug targets. They looked for characteristics like having no close human counterpart, being part of an essential metabolic pathway, and possessing a deep binding pocket where a drug molecule could attach. The discovery of these proteins is important because it provides a rich resource for developing new drugs against *Burkholderia* infections. Targeting these proteins with new drugs could disrupt the bacteria's functions, leading to their demise and ultimately treating the infections.

Why is this research important for the development of new antibiotics?

This research is essential for advancing antibiotic discovery. The article describes a new approach using functional and structural genomics to find new drugs. By combining these techniques and using strategies like "ortholog rescue", scientists have created a powerful platform to combat *Burkholderia* infections. The implications of this research are significant, as it could lead to the development of new antibiotics, offering hope in the fight against drug-resistant bacteria, and improving the treatment of diseases like melioidosis and severe pulmonary infections.