Abstract:Peptidoglycan is the major component of the cell envelope of virtually all bacteria. It has structural roles and acts as a selective sieve for molecules from the outer environment. Peptidoglycan synthesis is therefore one of the most important biogenesis pathways in bacteria and has been studied extensively over the last twenty years. The pathway starts in the cytoplasm, continues in the cytoplasmic membrane and finishes in the periplasmic space, where the precursor is polymerized into the peptidoglycan layer.… Show more
“…In both Gram-positive and -negative bacteria, the cell wall comprises a layer of the cross-linked polymer peptidoglycan (PG), which is composed of polysaccharides with alternating N -acetylglucosamine (GlcNAc) and N- acetylmuramic acid (MurNAc) saccharide groups. PG synthesis begins in the cytoplasm, where UDP-GlcNAc is synthesized from fructose-6-phosphate by the Glm enzymes, while UDP- N -acetylmuramyl-pentapeptide is synthesized from UDP-GlcN by the Mur enzymes (MurA, MurB, MurC, MurD, MurE and MurF) [43,44]. The proteins that catalyze the final steps of the PG synthesis include the bifunctional penicillin-binding proteins (PBPs), which catalyze the polymerization of the glycan strand (transglycosylation) and the cross-linking between glycan chains (transpeptidation).…”
The live attenuated Brucella melitensis Rev.1 Elberg-originated vaccine strain has been widely used to control brucellosis in small ruminants. However, despite extensive research, the molecular mechanisms underlying the attenuation of this strain are still unknown. In the current study, we conducted a comprehensive comparative analysis of the whole-genome sequence of Rev.1 against that of the virulent reference strain, B. melitensis 16M. This analysis revealed five regions of insertion and three regions of deletion within the Rev.1 genome, among which, one large region of insertion, comprising 3,951 bp, was detected in the Rev.1 genome. In addition, we found several missense mutations within important virulence-related genes, which may be used to determine the mechanism underlying virulence attenuation. Collectively, our findings provide new insights into the Brucella virulence mechanisms and, therefore, may serve as a basis for the rational design of new Brucella vaccines.
“…In both Gram-positive and -negative bacteria, the cell wall comprises a layer of the cross-linked polymer peptidoglycan (PG), which is composed of polysaccharides with alternating N -acetylglucosamine (GlcNAc) and N- acetylmuramic acid (MurNAc) saccharide groups. PG synthesis begins in the cytoplasm, where UDP-GlcNAc is synthesized from fructose-6-phosphate by the Glm enzymes, while UDP- N -acetylmuramyl-pentapeptide is synthesized from UDP-GlcN by the Mur enzymes (MurA, MurB, MurC, MurD, MurE and MurF) [43,44]. The proteins that catalyze the final steps of the PG synthesis include the bifunctional penicillin-binding proteins (PBPs), which catalyze the polymerization of the glycan strand (transglycosylation) and the cross-linking between glycan chains (transpeptidation).…”
The live attenuated Brucella melitensis Rev.1 Elberg-originated vaccine strain has been widely used to control brucellosis in small ruminants. However, despite extensive research, the molecular mechanisms underlying the attenuation of this strain are still unknown. In the current study, we conducted a comprehensive comparative analysis of the whole-genome sequence of Rev.1 against that of the virulent reference strain, B. melitensis 16M. This analysis revealed five regions of insertion and three regions of deletion within the Rev.1 genome, among which, one large region of insertion, comprising 3,951 bp, was detected in the Rev.1 genome. In addition, we found several missense mutations within important virulence-related genes, which may be used to determine the mechanism underlying virulence attenuation. Collectively, our findings provide new insights into the Brucella virulence mechanisms and, therefore, may serve as a basis for the rational design of new Brucella vaccines.
В опытах in vitro изучено действие эмоксипина и мексидола (метилэтилпиридинола гидрохлорид и сукцинат) на развитие культур эталонных штаммов Staphylococcus aureus АТСС 25923, Staphylococcus epidermidis АТСС 14990, Escherichia coli АТСС 25922 и Candida albicans АТСС 10231, а также исследована чувствительность микроорганизмов к их комбинациям с антимикробными средствами. Показано, что оба препарата проявляют сходное противомикробное действие в отношении использованных штаммов микроорганизмов с минимальной подавляющей концентрацией 1250 – 10000 мкг/мл. При комбинировании с другими антимикробными средствами эмоксипин (1000 мкг/диск) повышает чувствительность Escherichia coli АТСС 25922 к цефтазидиму и тетрациклину в равной мере в среднем на 91 % (p < 0,01 и p < 0,005). В этих условиях мексидол (1000 мкг/диск) увеличивает чувствительность Escherichia coli АТСС 25922 к цефтазидиму на 40 % p < 0,01 и повышает чувствительность Staphylococcus aureus АТСС 25923 к ванкомицину в среднем на 60 % (p < 0,001), цефтазидиму – на 54 % (p < 0,02), фузидину — на 40 % (p < 0,05) и норфлоксацину — на 21 % (p < 0,05). Собственное противомикробное действие и синергизм с традиционными антимикробными средствами следует учитывать при клиническом применении эмоксипина и мексидола при инфекционных заболеваниях и гнойных процессах.
“…Peptidoglycan helps maintain cell shape and serves as an anchor for accessory proteins and other cell wall components. As essential components of the cell wall, enzymes contributing to the peptidoglycan biosynthetic pathway can be exploited as antibiotic targets [41, 42]. …”
Section: Structural Basis Of Interfacial Lipid Modificationmentioning
confidence: 99%
“…Lipid II is then flipped across the membrane to the periplasm where its sugars are polymerized to form the glycan strands of the peptidoglycan mesh. MraY is the enzyme catalyzing the Lipid I synthesis [42]. MraY belongs to the polyprenylphosphate N -acetyl hexosamine 1-phosphate transferase (PNPT) superfamily of enzymes, which includes other potential antibiotic targets, WecA and TarO, enzymes responsible for bacterial cell wall synthesis.…”
Section: Structural Basis Of Interfacial Lipid Modificationmentioning
confidence: 99%
“…Lipid I, synthesized by MraY as previously discussed, is further modified to Lipid II by the addition of a GlcNAc moiety. Lipid II is then flipped across the membrane to the periplasm where an enzyme with transglycosylase activity transfers sugars from donor Lipid II molecules to a growing glycan chain (on a Lipid II starter molecule) and the peptides are linked by an enzyme with transpeptidase activity to form the final peptidoglycan mesh [42]. TG, in the simple case, catalyzes the transfer of the disaccharide peptide unit from a donor Lipid II to an acceptor Lipid II, forming Lipid IV.…”
Section: Structural Basis Of Extramembrane Lipid Modificationmentioning
The membrane-water interface forms a uniquely heterogeneous and geometrically constrained environment for enzymatic catalysis. Integral membrane enzymes sample three environments – the uniformly hydrophobic interior of the membrane, the aqueous extramembrane region, and the fuzzy, amphipathic interfacial region formed by the tightly packed headgroups of the components of the lipid bilayer. Depending on the nature of the substrates and the location of the site of chemical modification, catalysis may occur in each of these environments. The availability of structural information for alpha-helical enzyme families from each of these classes, as well as several beta-barrel enzymes from the bacterial outer membrane, has allowed us to review here the different ways in which each enzyme fold has adapted to the nature of the substrates, products, and the unique environment of the membrane. Our focus here is on enzymes that process lipidic substrates.
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