- Bacterial Genetics and Biotechnology
- Bacterial biofilms and quorum sensing
- Legume Nitrogen Fixing Symbiosis
- Vibrio bacteria research studies
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- Genomics and Phylogenetic Studies
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Cassava research and cyanide
- Plant-Microbe Interactions and Immunity
- Retirement, Disability, and Employment
- Plant nutrient uptake and metabolism
- Erythrocyte Function and Pathophysiology
- Microbial Metabolic Engineering and Bioproduction
- Microbial Community Ecology and Physiology
- Healthcare Systems and Practices
- Health, Medicine and Society
- Enzyme Structure and Function
- Blood properties and coagulation
Harvard University
2017-2024
University of Lausanne
2023-2024
Boston VA Research Institute
2019-2024
University of Geneva
2011-2021
Several regulators are involved in the control of cell cycle progression bacterial model system Caulobacter crescentus, which divides asymmetrically into a vegetative G1-phase (swarmer) and replicative S-phase (stalked) cell. Here we report novel functional interaction between enigmatic regulator GcrA N6-adenosine methyltransferase CcrM, both highly conserved proteins among Alphaproteobacteria, that activated early at end S-phase, respectively. As no direct biochemical regulatory...
Zinc-finger domain transcriptional regulators regulate a myriad of functions in eukaryotes. Interestingly, ancestral versions (MucR) from Alpha-proteobacteria control bacterial virulence/symbiosis. Whether virulence can also cell cycle transcription is unknown. Here we report that MucR proteins implement hitherto elusive primordial S→G1 switch. After charting G1-specific promoters the model Caulobacter crescentus by comparative ChIP-seq, use one such promoter as genetic proxy to unearth two...
In natural environments, bacteria often adhere to surfaces where they form complex multicellular communities. Surface adherence is determined by the biochemical composition of cell envelope. We describe a novel regulatory mechanism which bacterium, Caulobacter crescentus, integrates cycle and nutritional signals control development an adhesive envelope structure known as holdfast. Specifically, we have discovered 68-residue protein inhibitor holdfast (HfiA) that directly targets conserved...
What are the minimal requirements to sustain an asymmetric cell cycle? Here we use mathematical modelling and forward genetics reduce cycle its simplest, primordial components. In Alphaproteobacterium Caulobacter crescentus, progression is believed be controlled by a cyclical genetic circuit comprising four essential master regulators. Unexpectedly, our in silico predicted that one of these regulators, GcrA, fact dispensable. We confirmed this experimentally, finding ΔgcrA cells viable, but...
Several important human pathogens are represented in the Corynebacterineae suborder, including Mycobacterium tuberculosis and Corynebacterium diphtheriae. These bacteria surrounded by a multilayered cell envelope composed of cytoplasmic membrane, peptidoglycan (PG) wall, second polysaccharide layer called arabinogalactan (AG), finally an outer membrane-like made mycolic acids. anti-tuberculosis drugs target biogenesis this complex envelope, but their efficacy is declining due to resistance....
Eukaryotic morphogenesis is seeded with the establishment and subsequent amplification of polarity cues at key times during cell cycle, often using (cyclic) nucleotide signals. We discovered that flagellum de- repolarization in model prokaryote Caulobacter crescentus precisely orchestrated through least three spatiotemporal mechanisms integrated TipF. show TipF a cycle-regulated receptor for second messenger—bis-(3′–5′)-cyclic dimeric guanosine monophosphate (c-di-GMP)—that perceives...
Significance Penicillin-binding proteins (PBPs) are synthases that build the bacterial cell wall. They one of our most important antibiotic targets. Several years ago, it was shown a major PBP synthase Gram-negative bacterium Escherichia coli requires activation by LpoB. This outer-membrane lipoprotein is narrowly conserved in species whereas its target broadly distributed. Here, we show Pseudomonas aeruginosa and other bacteria use distinct called LpoP to activate their PBPs via mechanism...
Despite the crucial role of bacterial capsules in pathogenesis, it is still unknown if systemic cues such as cell cycle can control capsule biogenesis. In this study, we show that synchronizable model bacterium Caulobacter crescentus regulated and unearth a transglutaminase homolog, HvyA, restriction factor prevents capsulation G1-phase cells. This protects cells from infection by generalized transducing phage (φCr30), loss HvyA confers insensitivity towards φCr30. Control during could serve...
Heritable DNA methylation imprints are ubiquitous and underlie genetic variability from bacteria to humans. In microbial genomes, has been implicated in gene transcription, replication repair, nucleoid segregation, transposition virulence of pathogenic strains. Despite the importance local (hypo)methylation at specific loci, how when these patterns established during cell cycle remains poorly characterized. Taking advantage small genomes synchronizability α-proteobacteria, we discovered that...
Peptidoglycan (PG) is an essential cross-linked polymer that surrounds most bacterial cells to prevent osmotic rupture of the cytoplasmic membrane. Its synthesis relies on penicillin-binding proteins, targets beta-lactam antibiotics. Many Gram-negative bacteria, including opportunistic pathogen Pseudomonas aeruginosa, are resistant beta-lactams because a chromosomally encoded beta-lactamase called AmpC. In P. expression ampC gene tightly regulated and its induction linked cell wall stress....
ABSTRACT Pseudomonas aeruginosa encodes the beta-lactamase AmpC, which promotes resistance to beta-lactam antibiotics. Expression of ampC is induced by anhydro-muropeptides (AMPs) released from peptidoglycan (PG) cell wall upon treatment. AmpC can also be via genetic inactivation PG biogenesis factors such as endopeptidase DacB that cleaves crosslinks. Mutants in dacB occur beta-lactam-resistant clinical isolates P. , but it has remained unclear why induction. Similarly, lytic...
Rhizobia are a disparate collection of soil bacteria capable reducing atmospheric nitrogen in symbiosis with legumes (Fix phenotype). Synthesis the nitrogenase and its accessory components is under transcriptional control key regulator NifA generally restricted to endosymbiotic forms rhizobia known as bacteroids. Amongst studied rhizobia, Sinorhizobium fredii strain NGR234 has remarkable ability fix association more than 130 species 73 legume genera that form either determinate,...
Abstract Heritable DNA methylation imprints are ubiquitous and underlie genetic variability from bacteria to humans. In microbial genomes, has been implicated in gene transcription, replication repair, nucleoid segregation, transposition virulence of pathogenic strains. Despite the importance local (hypo)methylation at specific loci, how when these patterns established during cell cycle remains poorly characterized. Taking advantage small genomes synchronizability α-proteobacteria, we...
ABSTRACT Pseudomonas aeruginosa encodes the beta-lactamase AmpC, which promotes resistance to beta-lactam antibiotics. Expression of ampC is induced by fragments peptidoglycan (PG) cell wall released upon treatment. These drugs target transpeptidase enzymes that form crosslinks. However, they do not block activity transglycosylases polymerize glycan chains. Thus, drug-treated cells produce uncrosslinked PG polymers have been shown be rapidly degraded in related gram-negative bacterium...
Abstract The signals feeding into bacterial S-phase transcription are poorly understood. Cellular cycling in the alpha-proteobacterium Caulobacter crescentus is driven by a complex circuit of at least three transcriptional modules that direct sequential promoter firing during G1, early and late S cell cycle phases. In alpha-proteobacteria, regulator GcrA CcrM methyltransferase epigenetically activate promoters division polarity genes fire S-phase. By evolving cells to differentiate absence...