Antibiotic Persistence: Dormant Bacteria and the Fight Against Resistance

Overview

This episode of Shortwave delves into the biology of antibiotic persistence, a phenomenon that challenges our conventional understanding of how antibiotics work and how resistance evolves. The host recounts the history of penicillin and frames the current threat: bacteria are not only evolving resistance, but some can survive treatment by slipping into dormant or chaotic states. The interview with Natalie Balabo, a biophysicist at the Hebrew University in Jerusalem, anchors the discussion in experimental evidence and actionable ideas for the future of antimicrobial therapy. The episode also situates antibiotic persistence within clinical contexts, emphasizing that in immunocompromised patients the persistence mechanism can amplify the risk of persistent infections and the emergence of resistant strains.

What is antibiotic persistence?

Balabo explains that persistence is different from classic resistance. Persistent bacteria “survive during the antibiotic treatment” by arresting their growth, entering a dormant state in which growth ceases and many antibiotics lose their effectiveness because most drugs target actively dividing cells. When antibiotics are removed, these dormant cells can resume growth, potentially causing relapse or reinfection. This dynamic creates a challenging timeline for treatment, as recovery can be prolonged and unpredictable. The host and Balabo discuss how clinicians often focus on resistance rather than persistence, a gap that can hinder patient outcomes in certain contexts.

"Antibiotic persistence can lead to antibiotic resistance." - Natalie Balabo

Lab findings and conceptual advances

The conversation centers on recent work (the host notes a 2026 paper) showing that dormancy is not a uniform, neatly organized state. Instead, dormancy can be chaotic, a byproduct of external stresses such as immune encounters or environmental pressures. Balabo uses a car crash analogy to describe how an acute event can halt bacterial growth, which, rather than hindering the bacteria, can create conditions that protect them from antibiotics and alter their subsequent behavior. The chaotic dormancy is linked to slower recovery times and an extended window where the infection persists, increasing opportunities for evolutionary steps toward resistance. The discussion also covers how dormant cells are buffered against host defenses and how their long-term persistence can contribute to relapse, especially in settings where the immune system is compromised.

"the chaos that is governing the recovery time of these bacteria." - Natalie Balabo

Implications for treatment and the path forward

The core takeaway is that tackling persistence requires strategies beyond simply stacking antibiotics. Balabo describes a paradigm shift: persistent cells often have more permeable membranes in chaotic dormancy, suggesting that membrane-targeting compounds could be deployed alongside traditional antibiotics before stopping treatment. The aim would be to eliminate survivors who might otherwise seed relapse and foster resistance. The host emphasizes that preventing re-emergence of persistence is critical for reducing the risk of resistance evolving to new drugs, particularly in infections that last longer or occur in patients with weakened immune systems. The episode closes by connecting research to potential clinical practice, underscoring the need for integrated approaches that address both persistence and resistance as intertwined challenges.

"their membrane is more permeable." - Natalie Balabo