Understanding bacterial fitness in specific environments, particularly through mechanisms such as persistence and resistance, is a key challenge in microbiology. Pathogenic bacteria often encounter unfavorable conditions, including exposure to antibiotics, a dynamic host environment, and various toxic compounds. To survive these conditions, bacteria employ diverse adaptive strategies. During infection, they modify their envelope structures and metabolism to persist within the host. In turn, host cells also shift their state to limit bacterial invasion. Among the various bacterial strategies, one of the most striking is the reduction of metabolic activity, which leads to the formation of persister cells. In addition to persistence, pathogenic bacteria also face repeated exposure to antibiotics and often develop resistance as a countermeasure. We are interested in how pathogenic bacteria adapt to and survive in these unfavorable environments, focusing on Staphylococcus aureus, Escherichia coli, and Mycobacterium abscessus.
We investigate how bacteria adapt to diverse host environments by identifying the essential genes required for survival and adaptation. We investigate various niches of host cells, including epithelial cells, endothelial cells, and phagocytes. Using genomic profiling (Tn-seq) and transcriptomic profiling (Dual RNA-seq), we aim to define the genetic and molecular mechanisms that drive these adaptive processes. Through these studies, we seek to uncover the mechanisms behind bacterial survival strategies within the host, contributing to a deeper understanding of bacterial pathogenesis and potential therapeutic targets. In parallel, we also explore how host cells respond and equip themselves to limit bacterial infection at each stage of the infection process.
We investigate the mechanisms of antibiotic resistance and identify new bacterial targets through genomic analysis and synthetic lethality approaches. In parallel, we aim to discover antimicrobials with novel mechanisms of action. We are also interested in identifying pathways and molecules that can resensitize antibiotic-resistant bacteria. To further understand resistance, we examine how bacterial metabolism changes during antibiotic exposure, with particular attention to persister cell formation and its metabolic regulation. In addition, we explore the conditions that trigger persister cell development, including host environments and bactericidal toxic compounds.
We investigate the structure, function, and biogenesis of the S. aureus cell envelope under host induced stress and antibiotic pressure. In particular, we are interested in the remodeling of peptidoglycan and capsule in response to these stresses, as a reshaped cell envelope can alter susceptibility to cell wall targeting antibiotics. We are also studying the formation of L-forms under various conditions, with a focus on proteins involved in envelope biogenesis and maintenance in S. aureus.
We study bacterial proteases under various conditions, including host environments, to understand their functional roles and regulatory mechanisms. Our research also extends to viral proteases, particularly those of coronaviruses, as we work to identify novel inhibitors with therapeutic potential. In parallel, we investigate bacterial proteases in the context of protein modification, aiming to elucidate their impact on cellular processes and bacterial physiology. Through these studies, we aim to deepen our understanding of protease function and identify potential strategies to modulate their activity in bacterial and viral infections.