DOI: 10.1073/pnas.1905291116

In the ever-evolving battle against bacterial infections, the role of reactive oxygen species (ROS) has become a focal point for scientists aiming to understand and improve the efficacy of antibiotic treatments. A groundbreaking study published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) by Aviram Rasouly and Evgeny Nudler explores the critical function of ROS as conduits of antibiotic lethality.

The Study

The study, referenced under DOI 10.1073/pnas.1905291116, evaluates how antibiotics—once united with the bacterial machinery—prompt a surge in reactive oxygen species, triggering a cascade of events leading to bacterial cell death. This research elucidates how ROS act as more than mere byproducts of cellular metabolism and distress. Instead, ROS are positioned as central actors in the deathly waltz initiated by antibiotic treatment.

The Findings

The authors noted that bactericidal antibiotics target essential processes within bacterial cells, such as DNA replication, cell wall synthesis, and protein production. In doing so, they inadvertently induce a spike in ROS levels within the cells. This phenomenon has been seen as inadvertently contributing to oxidative damage and cell death, building upon the seminal work of researchers like Kohanski et al. (2007) and Belenky et al. (2015), who established that antibiotics stimulate ROS production, which in turn contributes significantly to their killing effect.

Research also indicates that ROS-mediated bacterial cell death is a nuanced process. Depending on the antibiotic class and its primary target, the production of ROS and subsequent cellular outcomes can differ drastically. For example, the lethal action of aminoglycosides is distinct from the malfunctioning of cell wall synthesis caused by beta-lactam antibiotics, as noted by Davis (1988) and Cho et al. (2014), respectively.

The Long Arm of Antibiotics

The study’s authors aptly describe ROS as the “long arm” of antibiotics, highlighting their reach and impact that extend beyond the initial antibiotic-bacterial interaction. This metaphor underscores the critical role played by ROS in the overall antibacterial strategy of antibiotics, adding depth and complexity to our understanding of how antibiotics achieve their effects.

Implications for Antibiotic Treatment

This work has a profound impact on how we perceive antibiotic treatment and the development of antibiotic resistance. Studies such as Mustaev et al. (2014) show the sophisticated mechanisms by which bacteria can become resistant to drugs. By gaining insight into the role of ROS in antibiotic efficacy, medical practitioners and researchers can design more effective treatment strategies that leverage this knowledge, potentially offering new pathways to combat antibiotic-resistant bacteria, as suggested by the research of Vilchèze et al. (2017).

Combating Antibiotic Tolerance and Persistence

Antibiotic tolerance and persistence present significant clinical challenges, as bacteria in these states can withstand antibiotic onslaughts without undergoing genetic changes. The insights gained from this study into ROS production can inform new interventions against these formidable bacterial defenses. Works like those by Fridman et al. (2014), Brauner et al. (2016), and Meylan et al. (2018) have brought greater understanding to these phenomena, paving the way for targeted strategies that disrupt bacterial defensive adaptations.

Beyond Antibiotic Stress

The study also touches on the broader implications of ROS generation in bacterial cells, which extends beyond the context of antibiotic stress. Understanding the natural defense mechanisms of bacteria, such as those elucidated by Gusarov et al. (2009) and Shatalin et al. (2011), and the role of ROS in these processes can inform a range of applications.

Future Research

Further research, building on studies like Imlay (2003) about pathways of oxidative damage, is needed to fully exploit ROS generation in the design of next-generation antibiotic therapies. Moreover, the intricate interplay between bacterial repair mechanisms, oxidative stress, and antibiotic lethality should be further dissected.


1. Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, Collins JJ (2007) A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130:797–810. DOI: 10.1016/j.cell.2007.06.049
2. Belenky P, et al. (2015) Bactericidal antibiotics induce toxic metabolic perturbations that lead to cellular damage. Cell Reports 13:968–980. DOI: 10.1016/j.celrep.2015.09.059
3. Mustaev A, et al. (2014) Fluoroquinolone-gyrase-DNA complexes: Two modes of drug binding. J Biol Chem 289:12300–12312. DOI: 10.1074/jbc.M113.540286
4. Vilchèze C, et al. (2017) Enhanced respiration prevents drug tolerance and drug resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 114:4495–4500. DOI: 10.1073/pnas.1613215114
5. Imlay JA. (2003) Pathways of oxidative damage. Annu Rev Microbiol 57:395–418. DOI: 10.1146/annurev.micro.57.030502.090955


1. Bactericidal antibiotics ROS
2. Antibiotic efficacy
3. Antibiotic resistance ROS
4. Reactive oxygen species bacteria
5. Antibiotic treatment strategies

With these findings in the spotlight, the scientific community stands on the cusp of what may be a transformative era in the battle against pathogenic bacteria. Researchers and healthcare providers are given a fresh perspective on the multifaceted nature of antibiotic action and are better equipped to address the contemporary challenges posed by antibiotic resistance and tolerance.