Our research
We are driven by curiosity
We use systems biology approaches to study antimicrobial activity against bacteria, specially Gram-negative pathogens. We want to uncover how bacterial molecular networks rewire in response to antimicrobials, and how that changes across environments and genetic contexts. Our ultimate goal it to enable better treatment through advanced mechanistic knowledge.
Our projects
We combine basic microbiology, high-throughput screening and systems biology approaches to tackle our questions with a comprehensive perspective that extends beyond conventional drug targets. Current projects in our lab focus on understanding how Gram-negative bacteria sense and react to their immediate chemical environment, how antibiotics work in combination with other drugs or phages, and how harness bacterial immunity towards antimicrobials activity.
How do bacteria sense their chemical environment?
Illustration generated with ChatGPT image generation (OpenAI) and edited by the Brochado Lab.
Here we investigate how bacteria perceive and respond to the diverse chemical environments they encounter. By combining high-throughput chemical screening, genetics, and regulatory network analysis, these projects uncover how antibiotics, host-derived molecules, food compounds, and human-targeted drugs reshape bacterial transcriptional programs controlling transport, stress responses, virulence, and intrinsic antibiotic resistance. This work reveals previously unrecognized regulatory mechanisms (Binsfeld C. et al, PLOS Biology, 2025), identifies key ligand-responsive transcriptional regulators, and provides predictive frameworks linking chemical structure to bacterial responses. Together, these studies establish how environmental chemicals influence bacterial physiology and antimicrobial susceptibility, offering new opportunities to manipulate bacterial behaviour therapeutically.
Antibiotic interactions: phages and other drugs
Illustration generated with ChatGPT image generation (OpenAI) and edited by the Brochado Lab.
Antibiotics are central drugs of any modern health-care system. However, their efficacity is threatened by continuously rising antimicrobial resistance (AMR). Antibiotic combinations with other agents, for instance drugs or phages, provides an attractive alternative to overcome resistance (Brochado A.R. et al, Nature, 2018). We aim to uncover the molecular principles governing interactions between antibiotics and between antibiotics and bacteriophages. Using systematic high-throughput approaches across multiple bacterial pathogens (E. coli, Salmonella Typhimurium, Pseudomonas aeruginosa), we identify species-specific mechanisms underlying antibiotic synergy and antagonism, while introducing bacterial recovery dynamics as a new dimension for understanding combination therapy. In parallel, ongoing projects investigate how synergy and antagonism is shaped by host environments, in particular macrophages – immune cells that pathogens use to hide in our bodies and manipulate our immune system. Together, these projects provide a mechanistic framework for the rational design of pathogen-specific combination therapies.
Regulation of phage defence systems and its impact on antimicrobial activity
Bacteria are armed with powerful systems to protect themselves against phages (viruses of bacteria). We want to understand how bacterial phage defence systems are regulated, in particular in the absence of phages, and how they unexpectedly influence antibiotic activity. Our work demonstrated that the CBASS immune system can dramatically alter bacterial susceptibility to antibiotics by triggering self-destructive immune responses, effectively converting a bacteriostatic antibiotic into a killing one (Brenzinger S. et al, Nature Microbiology, 2024). Building on these discoveries, ongoing research seeks to systematically identify the genetic and environmental factors controlling abortive infection (Abi) systems across diverse bacterial backgrounds and environmental conditions (ERC CoG 2025). Ultimately, these studies aim to exploit bacterial immune systems as novel antimicrobial targets and develop strategies that harness immune activation to improve infection control.
Credit to Lizah van der Aart