Zinc and PBT2 breaking down bacterial resistance.

Zinc and PBT2: The Dynamic Duo that Could Beat Antibiotic Resistance

Theo Raines in Health & Wellness December 2025 • 3 min read.

"Can a novel combination of zinc and an ionophore called PBT2 offer a new approach to tackling resistant bacteria?"

Antibiotic resistance is an escalating global crisis, threatening to render common infections untreatable. The rise of 'superbugs' resistant to last-line antibiotics, coupled with a decline in new antibiotic development, demands innovative therapeutic strategies.

Researchers are exploring the potential of existing drugs initially developed for other conditions to combat bacterial resistance. One promising candidate is PBT2, a zinc ionophore tested in clinical trials for Alzheimer's and Huntington's disease.

A new study reveals the synergistic power of combining PBT2 with zinc to disrupt cellular homeostasis in resistant bacteria, effectively reversing antibiotic resistance in critical pathogens. This approach offers a new avenue for tackling antibiotic resistance, potentially revitalizing the effectiveness of existing treatments.

How PBT2 and Zinc Team Up Against Superbugs

Zinc and PBT2 breaking down bacterial resistance.

PBT2 is an ionophore, a molecule that facilitates the transport of ions across cell membranes. In this case, PBT2 helps zinc ions enter bacterial cells, disrupting their metal homeostasis. Bacteria carefully regulate the levels of metal ions inside their cells, and disrupting this balance can be toxic.

The study focused on Gram-positive bacteria, including:

Erythromycin-resistant group A Streptococcus (GAS)
Methicillin-resistant Staphylococcus aureus (MRSA)
Vancomycin-resistant Enterococcus (VRE)

These pathogens are significant threats in both community and hospital settings, known for their resistance to multiple antibiotics. Researchers found that PBT2-zinc, while not potent on its own, significantly enhanced the effectiveness of several antibiotics against these resistant strains. Moreover, they observed no development of resistance to the PBT2-zinc combination, suggesting a durable therapeutic strategy.

A New Hope for Fighting Resistant Infections

The study highlights a novel approach to combating antibiotic resistance: disrupting bacterial physiology to resensitize pathogens to existing drugs. By destabilizing metal ion homeostasis, PBT2-zinc weakens bacteria and allows antibiotics to regain their effectiveness.

While further research is needed to fully understand the mechanisms and optimize the use of PBT2-zinc, these findings offer a promising new strategy for tackling the growing threat of antibiotic resistance.

With PBT2 already proven safe for human use in other clinical trials, this research paves the way for potential new treatments that could significantly impact global healthcare and reduce the burden of resistant infections.

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: 10.1128/mbio.02391-18, Alternate LINK

Title: Chemical Synergy Between Ionophore Pbt2 And Zinc Reverses Antibiotic Resistance

Subject: Virology

Journal: mBio

Publisher: American Society for Microbiology

Authors: Lisa Bohlmann, David M. P. De Oliveira, Ibrahim M. El-Deeb, Erin B. Brazel, Nichaela Harbison-Price, Cheryl-Lynn Y. Ong, Tania Rivera-Hernandez, Scott A. Ferguson, Amanda J. Cork, Minh-Duy Phan, Amelia T. Soderholm, Mark R. Davies, Graeme R. Nimmo, Gordon Dougan, Mark A. Schembri, Gregory M. Cook, Alastair G. Mcewan, Mark Von Itzstein, Christopher A. Mcdevitt, Mark J. Walker

Published: 2018-12-21

Everything You Need To Know

How does combining zinc with PBT2 help in overcoming antibiotic resistance in superbugs?

The combination of zinc and PBT2 works by using PBT2, an ionophore, to transport zinc ions into bacterial cells. This influx of zinc disrupts the bacteria's metal homeostasis, which is the careful balance of metal ions inside the cell that is crucial for bacterial survival. By disrupting this balance, the bacteria are weakened, making them more susceptible to antibiotics.

What exactly is PBT2, and what was its original purpose before being explored for antibiotic resistance?

PBT2 is a zinc ionophore initially developed and tested in clinical trials for conditions like Alzheimer's and Huntington's disease. Its role is to facilitate the transport of zinc ions across cell membranes, specifically into bacterial cells. This action disrupts the bacteria's internal metal ion balance, leading to weakened resistance against antibiotics. PBT2's previous testing for other conditions suggests a level of safety for human use, making it a promising candidate in the fight against antibiotic resistance.

Which specific types of antibiotic-resistant bacteria are affected by the zinc and PBT2 combination?

The study specifically targeted Gram-positive bacteria known for their resistance to multiple antibiotics. These included Erythromycin-resistant group A Streptococcus (GAS), Methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococcus (VRE). These pathogens pose significant threats in both community and hospital settings. The PBT2-zinc combination was effective in enhancing the impact of existing antibiotics against these resistant strains.

Why is disrupting metal ion homeostasis a promising strategy for fighting antibiotic resistance?

Disrupting metal ion homeostasis in bacteria offers a novel approach to combating antibiotic resistance because it weakens the bacteria's defenses, making them more susceptible to existing antibiotics. This strategy can potentially resensitize pathogens to drugs that were previously ineffective due to resistance mechanisms. By focusing on bacterial physiology rather than directly targeting specific bacterial functions, this approach may also prove more durable, as it doesn't rely on traditional antibiotic mechanisms that bacteria can easily develop resistance to.

Is there any evidence to suggest that bacteria will not develop resistance to the PBT2 and zinc combination over time?

The research indicated that the combination of PBT2 and zinc did not lead to the development of resistance in the tested bacteria. This is a significant finding because it suggests that this therapeutic strategy could offer a more durable solution compared to traditional antibiotics, where resistance often develops rapidly. The absence of resistance development with the PBT2-zinc combination implies that it could be a valuable tool in the long-term fight against antibiotic-resistant infections.