Basic Microbiology
Philip A. Geis in Cosmetic Microbiology, 2020
Free-living bacteria require protection against osmotic stresses. Osmotic stress is encountered when bacteria enter hypotonic or hypertonic environments depending on the concentration of solutes within the cell. This can lead water to cross the plasma membrane by osmosis in an attempt to normalize solute concentrations across the membrane. Excess gain of water can cause the bacteria to lyse or explode due to cellular swelling whereas excess loss of water can cause membrane rupture by excessive shrinkage (plasmolysis). Most bacteria utilize a carbohydrate-based cell wall in order to provide resistance to osmotic forces. The basis of the cell wall is a macromolecular complex unique to bacteria called “peptidoglycan” or murein (Figure 1.4). The basic repeating structure of peptidoglycan is a disaccharide comprising N-acetylglucosamine (NAG) linked to N-acetylmuramic acid (NAM). This disaccharide is repeated hundreds of times to build long carbohydrate chains that are linked together by short peptides (called stem peptides) that contain unusual amino acids, some not found in proteins. These long chains appear to be wound into helices first and then cross-linked to other helices to form the peptidoglycan structure (2). The peptidoglycan is attached firmly to the cell membrane by lipoproteins. Although bacteria have proteins that determine the overall morphology of the cell, the peptidoglycan reinforces that morphology.
Basic science, investigations and lasers
Mostafa Khalil, Omar Kouli in The Duke Elder Exam of Ophthalmology, 2019
Bacteria are unicellular prokaryotic organisms that contain DNA and ribonucleic acid (RNA) freely in the cytoplasm. Reproduction is via a process called binary fission. Bacteria can be classified according to their morphology and gram staining (Table 1.3). Bacteria have various characteristics: Cell wall: Gram-positive bacterial cell walls are predominantly made of peptidoglycan (stains purple), while Gram-negative bacteria is predominantly made of an outer plasma membrane (stains pink).Cell membrane.Plasmids (fragments of DNA): Thought to be the reason behind antibiotic resistance.Flagella: Helps with motility.Pili: Transfers DNA between bacteria.Exotoxins and endotoxin: In Gram-positive and Gram-negative bacteria, respectively.
Biology of microbes
Philip A. Geis in Cosmetic Microbiology, 2006
Synthesis of peptidoglycan. Peptidoglycan consists of long polysaccharide chains made of N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG). Pentapeptide chains are attached to the NAM groups. The chains are then attached to each other either directly by the pentapeptide chains (Gram-negative bacteria) or via a pentaglycine bridge (Gram-positive bacteria). During synthesis of this complex cell wall constituent, two key carriers participate: uridine diphosphate (UDP) and bactoprenol. Bactoprenol is a large 55-carbon alcohol that attaches to the NAM by a pyrophosphate. It moves peptidoglycan subunits back and forth through the hydrophobic membrane.
Discovery of a fragment hit compound targeting D-Ala:D-Ala ligase of bacterial peptidoglycan biosynthesis
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Matic Proj, Martina Hrast, Gregor Bajc, Rok Frlan, Anže Meden, Matej Butala, Stanislav Gobec
Peptidoglycan is a macromolecule essential for bacterial survival and is found only in the bacterial cell wall. Therefore, enzymes involved in the peptidoglycan biosynthetic pathway represent potential targets for the discovery of new antimicrobial agents5,6. Among the intracellular enzymes involved in peptidoglycan biosynthesis, only two enzymes have been validated as antibacterial targets by inhibitors that are in clinical use: UDP-N-acetylglucosamine-enolpyruvyl transferase (MurA, EC 2.5.1.7) is validated by fosfomycin, which is used to treat urinary tract infections7, and D-alanine:D-alanine ligase (Ddl, EC 6.3.2.4) is validated by cycloserine (Figure 1(B)), which is a second-line drug for the treatment of tuberculosis8.
Ceftobiprole medocaril for the treatment of pneumonia
Published in Expert Review of Anti-infective Therapy, 2023
Wan-Hsuan Hsu, Chi-Kuei Hsu, Chih-Cheng Lai
First, ceftobiprole exerts its bactericidal activity by inhibiting transpeptidases, showing strong affinities to PBP 2a, PBP2×, and PBP3. PBP2a, PBP2×, and PBP3 are responsible for β-lactam drug resistance in MRSA, PRSP, and MSSA respectively [31]. In addition, it can interfere with peptidoglycan biosynthesis of the bacterial cell wall in order to kill antibiotic-resistant bacteria. Second, the plasma protein binding of ceftobiprole is minimal, and it can achieve high concentrations in excess of the MICs for the causative pathogens in the ELFs [25,26]. And third, ceftobiprole exhibits potent in vitro activity against a wide range of susceptible pathogens, including S. aureus, S. pneumoniae, Viridans streptococci, H. influenzae, M. catarrhalis, and Enterobacterales. Besides, both CA-MRSA and HA-MRSA were susceptible to ceftobiprole with an overall susceptibility rate of more than 99.2% [35,37,39,42]. P. aeruginosa, an important HAP-causing pathogen, has shown to be susceptible to ceftobiprole with a rate ranging from 62.4% to 86.0% [36–38,42]. Lastly, the clinical efficacy and safety of ceftobiprole in the treatment of pediatric and adult patients with CAP and HAP excluding VAP have been demonstrated by several RCTs (NCT00326287, NCT00210964, NCT00229008, NCT03439124) [47–49]. Further subgroup analysis and our meta-analysis demonstrated consistent findings.
Impact of chronic medications in the perioperative period: mechanisms of action and adverse drug effects (Part I)
Published in Postgraduate Medicine, 2021
Ofelia Loani Elvir-Lazo, Paul F White, Hillenn Cruz Eng, Firuz Yumul, Raissa Chua, Roya Yumul
Aminoglycosides inhibit bacterial protein synthesis by binding to the 16S rRNA component of the 30S ribosome subunit [56]. Beta-lactams (e.g. penicillins, cephalosporins, and carbapenems) and glycopeptides (e.g. vancomycin) interfere with specific steps in bacterial cell wall biosynthesis, resulting in cell lysis. Beta-lactams block the cross-linking of peptidoglycan units by inhibiting the peptide bond formation reaction catalyzed by penicillin-binding proteins (PBP). Vancomycin achieves the same inhibition by blocking the transglucosylase and PBP activity [56]. Fluoroquinolones inhibit DNA synthesis by targeting the enzyme DNA gyrase, which is a topoisomerase, which prevents bacteria from replicating its DNA. Cyclic lipopeptides (daptomycin) also inhibit cell wall synthesis by altering the structural integrity of bacteria by inserting themselves into the cell membrane and inducing membrane depolarization [57]. Nitroimidazoles (metronidazole) inhibits protein synthesis by forming cytotoxic nitro-radical anions that result in DNA strand breakage [58].
Related Knowledge Centers
- Bacteria
- Cytoplasm
- Oligopeptide
- Osmotic Pressure
- Polysaccharide
- Amino Acid
- N-Acetylglucosamine
- N-Acetylmuramic Acid
- Gram-Positive Bacteria
- Gram-Negative Bacteria