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Discovered in the mid 80s, ramoplanin shows activity against Gram positive bacteria such as Streptococcus, Staphylococcus, Enterococcus and Clostridium species. It binds to lipid II, inhibiting thereby the transglycosylase activity of PBPs. Its mode of action is therefore different from that of other antibiotics acting on cell wall synthesis (β-lactams, glycopeptides, bacitracin, fosfomycin, …)
At the moment, no mutations in enzymes responsible for lipid II synthesis were evidenced (except in in vitro experiments with Mycobacterium and in vivo in s. pneumoniae, but this are rare). This may explain that no resistance has been evidences in the clinics so far. It has been shown that bacteria exposed to stress (oxidative stress, antibiotics acting on cell wall) can activate a system that reinforces the cell wall.
in spite of its broad spectrum and low MICs for Gram positive bacteria, current clinical studies are focused on C. difficile infection and eradication of vancomycin resistant enterococci from the intestine (to prevent bacteraemia and risks of endocarditis, osteomyelitis, renal infection …). Ramoplanin could constitute an alternative to metronidazole and vancomycin (clostridium) and to the association penicillin G/gentamicin, linezolid, the streptogramin suinopristin/dalfopristin (VRE), or vancomycin in enterococcal infections, because of its action on multiresistant bacteria (MRSA, VRE and clostridium). Animal studies also suggest efficacy against endocarditis (in association with penicillin) and catheter infection Découverte au milieu des années 80, la ramoplanine a montré une activité sur un large spectre de bactérie gram positives (streptocoque, staphylocoque, entérocoque, clostridium). Son mode d’action, par inhibition des transglycosylases des PBP (après liaison au lipide II), la différentie des autres antibiotiques interagissant avec la synthèse de la paroi (glycopeptide, β-lactame, bacitracine, fosfomycine,…). De plus cette cible a peu de chance de muter car jusqu’à présent, aucune mutation n’a été observé au niveau du lipide II (sauf expérimentalement sur des mycobactérie et naturellement sur Streptococcus pneumoniae mais ceci est marginal). Ce qui explique la non apparition de souche résistante jusqu'à présent. Pourtant, en réponse à une perturbation de la paroi par un stress (stress oxydatif, antibiotique ciblant la paroi,…), on a observé l’activation d’un système qui permet à la bactérie de renforcer la paroi.
Malgré son large spectre et ces CMI basses pour les bactéries gram positives, la ramoplanine n’est en étude clinique que pour les infections à Clostridium difficile et l’éradication des entérocoques résistant à la vancomycine se trouvant dans les intestins (pour éviter un bactériémie amenant à l’endocardite, ostéomyélite, infection des reins,…). Elle pourait constituer un second choix après le métronidazole ou la vancomycine dans le cas de clostridium difficile et après l’association pénicilline G/gentamicine, le linezolide, l’association quinopristine/ dalfopristine ou la vancomycine dans le cas des entérocoques, car elle reste active sur les souches multi résistantes (MRSA, VRE, Clostridium). Lors des tests sur animaux, elle s’est également montrée active pour traiter l’endocardite (en association avec le pénicilline) et les ifnections sur cathéters

Anti-Bacterial Agents --- ramoplanin --- Peptidoglycan

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CELL CYCLE. --- ESCHERICHIA COLI, cytology. --- PEPTIDOGLYCAN, biosynthesis.

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The Planctomycetes, Verrucomicrobia, Chlamydiae (PVC) and related phyla have recently emerged as fascinating subjects for research in evolutionary cell biology, ecology, biotechnology, evolution and human health. This interest is prompted by particular characteristics observed in the PVC superphylum that are otherwise rarely observed in bacteria but are however still poorly described or understood, such as the presence of a complex endomembrane system, or compacted DNA throughout most of the cell cycle. Therefore, the members of the PVC superphylum represent an excellent example of the value of studying bacteria other than ‘classical’ models.

genetic tools --- peptidoglycan --- PVC bacteria --- cell biology and cell division --- cell surface --- bioactive compounds

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

PVC bacteria --- bioactive compounds --- Peptidoglycan --- cell surface --- Genetic tools --- cell biology and cell division

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Science: general issues --- Medical microbiology & virology --- Microbiology (non-medical) --- bacterial cell wall --- peptidoglycan synthesis --- cell wall dynamics --- cell wall turnover --- cell wall modification --- peptidoglycan recycling --- autolysins --- cell wall degradation --- antibiotic target