Antibiotic-Mediated Cellular Responses in Bacterial Systems

Antibiotic exposure triggers multifaceted cellular programmes in bacteria that extend beyond simple target inhibition. Primary drug–target interactions, such as blockade of cell wall synthesis or DNA replication, initiate secondary stress responses encompassing DNA damage repair, envelope stress signalling and oxidative stress. These adaptive circuits often involve global transcriptional regulators, small-molecule second messengers and metabolic rewiring, all of which contribute to survival, persistence and the emergence of resistance. Bacterial metabolic homeostasis is profoundly altered under antibiotic pressure: shifts in central carbon flux, proton motive force and redox balance can determine the fate of individual cells, biasing populations towards death, dormancy or mutation. Moreover, interactions with host immunity—particularly complement-mediated lysis—can be modulated by antibiotic-induced changes in surface antigens and secreted effectors. Understanding these interconnected responses is crucial for devising adjuvant therapies that potentiate antibiotic efficacy, reverse resistance and limit the global spread of multidrug-resistant pathogens.

Research from Nature Portfolio

Recent studies have revealed that exogenous metabolites can reprogramme bacterial physiology to synergise with innate immunity. In particular, supplementing glycine was shown to redirect metabolic fluxes towards the Krebs cycle and purine synthesis, leading to enhanced expression of complement-binding surface proteins. This metabolic shift promotes assembly of the membrane attack complex on resistant Escherichia coli strains, restoring serum sensitivity both in vitro and in vivo. These findings highlight the potential of targeted metabolite interventions as adjuvants to conventional antibiotics and immune clearance.

Antibiotic-Mediated Cellular Responses in Bacterial Systems publication trend

The graph below shows the total number of articles in antibiotic-mediated cellular responses in bacterial systems across all publications each year (not limited to Nature Index journals).

Technical terms

SOS response: A global DNA damage-repair and mutagenic pathway induced by genotoxic stress, involving RecA-mediated LexA cleavage and expression of repair enzymes.

Complement attack complex (MAC): A multimeric assembly of complement proteins that inserts into bacterial membranes, causing lysis.

Metabolic flux: The rate of turnover through a metabolic pathway, determining the distribution of intermediates and energy production.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen (e.g. superoxide, hydrogen peroxide) that can damage cellular components.

Proton motive force: The electrochemical gradient of protons across a membrane that drives ATP synthesis, nutrient uptake and motility.

References

1. Heterogeneity of SOS response expression in clinical isolates of Escherichia coli influences adaptation to antimicrobial stress. Drug Resistance Updates (2024).
2. Bacterial Metabolism and Antibiotic Efficacy. Cell Metabolism (2019).
3. Glycine, serine and threonine metabolism confounds efficacy of complement-mediated killing. Nature Communications (2019).
4. Reactive Oxygen Species in Pathogen Clearance: The Killing Mechanisms, the Adaption Response, and the Side Effects. Frontiers in Microbiology (2021).