As scientists continue to unravel the mysteries of the human microbiome, a team of researchers has made a groundbreaking discovery about the lung bacteria Pandoraea. These microbes have long been associated with disease-causing properties, but new research reveals that they also possess remarkable survival strategies, including the ability to forge iron-stealing weapons to thrive in challenging environments.

At the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), researchers led by Elena Herzog have been studying Pandoraea bacteria, which are known to be pathogenic but also produce natural products with antibacterial effects. The team’s investigation has shed light on how these bacteria manage to survive in iron-poor environments within the human body.

Iron plays a vital role in living organisms, including bacteria, as it is essential for enzymes and the respiratory chain. However, in environments like the human body, where iron is scarce, microorganisms must adapt to compete for this essential resource. Pandoraea bacteria have developed a unique strategy by producing siderophores – small molecules that bind iron from their environment and transport it into the cell.

The researchers identified a previously unknown gene cluster called pan, which codes for a non-ribosomal peptide synthetase enzyme responsible for the production of siderophores. Through targeted inactivation of genes and advanced analytical techniques, they isolated two new natural products, Pandorabactin A and B, which can complex iron and play an important role in how Pandoraea strains survive.

Moreover, bioassays revealed that pandorabactins inhibit the growth of other bacteria by removing iron from these competitors. The researchers also analyzed sputum samples from cystic fibrosis patients, finding that the detection of the pan gene cluster correlates with changes in the lung microbiome. This suggests that pandorabactins could have a direct influence on microbial communities in diseased lungs.

While the study’s findings are still preliminary and not yet suitable for medical applications, they provide valuable insights into the survival strategies of Pandoraea bacteria and the complex competition for vital resources within the human body. As researchers continue to explore the intricacies of the microbiome, this discovery paves the way for further investigation and potentially innovative treatments in the future.

The World Health Organization (WHO) reports that antimicrobial resistance causes more than 1 million deaths every year and contributes to over 35 million additional illnesses. Gram-positive pathogens like Staphylococcus aureus and Enterococcus can cause severe hospital-acquired and community-acquired infections, making the development of effective treatments a pressing concern.

Researchers have recently discovered a synthetic compound called infuzide that shows promise against antimicrobial resistant strains of S. aureus and Enterococcus in laboratory and mouse tests. Infuzide was synthesized as part of a decade-long project by interdisciplinary researchers looking for ways to create compounds that could act against pathogens in ways similar to known pharmaceuticals.

“We started the project as a collaboration, looking for ways to synthesize compounds and connecting them with compounds that might have biological activities,” said medicinal chemist Michel Baltas, Ph.D., from the Laboratoire de Chimie de Coordination at the University of Toulouse in France. Baltas co-led the new work, along with Sidharth Chopra, Ph.D., from the CSIR-Central Drug Research Institute in Lucknow, India.

The researchers found that infuzide specifically attacks bacterial cells and is more effective than the standard antibiotic vancomycin in reducing the size of bacterial colonies in lab tests. In tests of resistant S. aureus infections on the skin of mice, the compound effectively reduced the bacterial population, with an even higher reduction when combined with linezolid.

While infuzide did not show significant activity against gram-negative pathogens, the researchers are exploring small changes to expand its antimicrobial activity. The simplicity of the chemical reactions involved in synthesizing infuzide also makes it easy to scale up production for new treatments.

In addition to its potential against multidrug resistance, the group has been investigating the effects of synthesized compounds on other infectious diseases, including tuberculosis. “We have many other candidates to make antimicrobial compounds,” Baltas said.

In a groundbreaking study led by researchers at RMIT University in Australia, a protein that gives fleas their remarkable elasticity has been used to prevent bacterial infection on medical implants. The resilin-mimetic proteins, which are derived from the insect resilin, have shown 100% effectiveness in repelling E.coli bacteria and human skin cells in lab conditions.

The study’s lead author, Professor Namita Roy Choudhury, said that this finding is a crucial step towards creating smart surfaces that stop dangerous bacteria, especially antibiotic-resistant ones like MRSA, from growing on medical implants. “This work shows how these coatings can be adjusted to effectively fight bacteria – not just in the short term, but possibly over a long period,” she added.

The potential applications of this research are vast and include spray coatings for surgical tools, medical implants, catheters, and wound dressings. The resilin-mimetic proteins have exceptional properties such as elasticity, resilience, and biocompatibility, making them ideal for many applications requiring flexible, durable materials and coatings.

Study lead author Dr Nisal Wanasingha said that the nano droplets’ high surface area made them especially good at interacting with and repelling bacteria. “Once they come in contact, the coating interacts with the negatively charged bacterial cell membranes through electrostatic forces, disrupting their integrity, leading to leakage of cellular contents and eventual cell death,” he explained.

Unlike antibiotics, which can lead to resistance, the mechanical disruption caused by the resilin coatings may prevent bacteria from establishing resistance mechanisms. Meanwhile, resilin’s natural origin and biocompatibility reduce the risk of adverse reactions in human tissues, making them more environmentally friendly than alternatives based on silver nanoparticles.

Future work includes attaching antimicrobial peptide segments during recombinant synthesis of resilin-mimics and incorporating additional antimicrobial agents to broaden the spectrum of activity. Transitioning from lab research to clinical use will require ensuring the formula’s stability and scalability, conducting extensive safety and efficacy trials, while developing affordable production methods for widespread distribution.

The study was in collaboration with the ARC Centre of Excellence for Nanoscale BioPhotonics and the Australian Nuclear Science and Technology Organisation (ANSTO). The team used ANSTO’s Australian Centre for Neutron Scattering facilities, and RMIT University’s Micro Nano Research Facility and Microscopy and Microanalysis Facility. The work was funded by the Australia India Strategic Research Fund, Australian Institute of Nuclear Science and Engineering top-up Postgraduate Research Award (PGRA) and supported by the Australian Research Council.