Molecular mechanisms underlying the structural diversity of rhamnose-rich cell wall polysaccharides in lactococci.

In Gram-positive bacteria, cell wall polysaccharides (CWPS) play critical roles in bacterial cell wall homeostasis and bacterial interactions with their immediate surroundings. In lactococci, CWPS consist of two components: a conserved rhamnan embedded in the peptidoglycan layer and a surface-exposed polysaccharide pellicle (PSP), which are linked together to form a large rhamnose-rich CWPS (Rha-CWPS). PSP, whose structure varies from strain to strain, is a receptor for many bacteriophages infecting lactococci.

Amino-acyl tXNA as inhibitors or amino acid donors in peptide synthesis.

Xenobiotic nucleic acids (XNAs) offer tremendous potential for synthetic biology, biotechnology, and molecular medicine but their ability to mimic nucleic acids still needs to be explored. Here, to study the ability of XNA oligonucleotides to mimic tRNA, we synthesized three L-Ala-tXNAs analogs. These molecules were used in a non-ribosomal peptide synthesis involving a bacterial Fem transferase.

New MraY Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole.

New inhibitors of the bacterial transferase MraY from (MraY), based on the aminoribosyl uridine central core of known natural MraY inhibitors, have been designed to generate interaction of their oxadiazole linker with the key amino acids (H324 or H325) of the enzyme active site, as observed for the highly potent inhibitors carbacaprazamycin, muraymycin D2 and tunicamycin. A panel of ten compounds was synthetized notably thanks to a robust microwave-activated one-step sequence for the synthesis of the oxadiazole ring that involved the -acylation of an amidoxime and subsequent cyclization. The synthetized compounds, with various hydrophobic substituents on the oxadiazole ring, were tested against the MraY transferase activity.

Towards discovery of inhibitors of the undecaprenyl-pyrophosphate phosphatase BacA by virtual high-throughput screening.

Increasing resistance to common antibiotics is becoming a major challenge that requires the development of new antibacterial agents. Peptidoglycan is an essential heteropolymer of the bacterial envelope that ensures the integrity and shape of all bacteria and is also an important target for antibiotics. The biosynthesis of peptidoglycan depends on a lipid carrier, undecaprenyl phosphate.

The Biology of Colicin M and Its Orthologs.

The misuse of antibiotics during the last decades led to the emergence of multidrug resistant pathogenic bacteria. This phenomenon constitutes a major public health issue. Consequently, the discovery of new antibacterials in the short term is crucial.