ANTIMICROBIAL AGENTS
Antimicrobial Agents
A structured M4S chapter covering antimicrobial agents and their classification according to the microbial target or site of action, with emphasis on antibacterial cell-wall and cell-membrane inhibitors.
Antimicrobial Agents
⌄Antimicrobial agents or antibiotics are naturally occurring substances produced by microorganisms to inhibit other microorganisms. Synthetic compounds should be referred to as chemotherapeutic agents. Examples are sulphonamides, quinolones, nitrofurans, imidazoles, etc. However, there are semi-synthetic antibiotics which are chemically modified forms of naturally occurring antibiotics. Thus, the term antibiotics is used broadly to describe agents utilized to treat systemic infection.
Types of Antimicrobial Agents
⌄There is a huge diversity of antimicrobial agents. So, it is convenient to classify them according to their mode of action on the site whereupon they act to inhibit microbial growth, especially in human infections.
| Major group | Classes/subclasses listed in the source |
|---|---|
| A) Antibacterial agents | Cell-wall synthesis inhibitors; cell-membrane inhibitors; protein-synthesis inhibitors; nucleic-acid synthesis inhibitors; other antibacterial agents. |
| B) Antifungal agents | Listed as a major group. |
| C) Antiviral agents | Nucleoside analogue; non-nucleoside analogue; viral-uncoating inhibitors; neuraminidase inhibitors; interferons; nucleoside/nucleotide reverse transcriptase inhibitors; non-nucleoside reverse transcriptase inhibitors. |
| D) Antiparasitic agents | Listed as a major group. |
Antibacterial Agents: Inhibitors of Bacterial Cell-wall Synthesis
⌄Three phases make up the intricate process of cell wall biosynthesis, which involves several different proteins. The three stages are known as the cytoplasmic, membrane-associated, and exocytoplasmic stages [9].
The peptidoglycan components of the cell walls of many bacteria, both Gram-positive and Gram-negative, are recycled in large quantities during growth and septation [1]. Currently, beta-lactam antibiotics such as penicillin and cephalosporins that prevent production of the peptidoglycan layer, and glycopeptide antibiotics such as vancomycin and teicoplanin that interfere with assembly of the peptidoglycan precursor lipid II, are described as the main inhibitors of cell-wall synthesis.
Cytoplasmic Stage Inhibitors
⌄The major antibiotics that interfere with the cytoplasmic stage include D-cycloserine and fosfomycin.
| Agent | Target stated in source | Key description |
|---|---|---|
| D-cycloserine | D-Ala–D-Ala ligase and alanine racemase | Interferes with enzymes involved in the cytoplasmic stage. |
| Fosfomycin | MurA | Inhibits the initial stage of cell-wall production by binding UDP-N-acetylglucosamine-3-enolpyruvyl transferase (MurA) and mimicking the substrate phosphoenolpyruvate. |
Fosfomycin is described in the source as a broad-spectrum bactericidal antibiotic effective against both Gram-positive and Gram-negative infections, with examples including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus sp.
Membrane-associated Stage Inhibitors
⌄The supplied content states that uridyl peptides (tunicamycin) and ramoplanin interfere with the membrane-associated stage.
| Agent | Target stated in source |
|---|---|
| Uridyl peptides (tunicamycin) | MraY |
| Ramoplanin | MurG and lipid II |
Exocytoplasmic Stage Inhibitors
⌄The source lists the following agents and targets for interference with the extracytoplasmic stage:
| Antimicrobial class/agent | Target stated in source |
|---|---|
| β-Lactams | PBPs |
| Glycopeptides | Lipid II and d-Ala–d-Ala terminal |
| Moenomycin | Transglycosylase |
| Mannopeptimycins | Lipid II |
| Lantibiotics (nisin) | Lipid II |
| Defensin (plectasin) | Lipid II |
| Bacitracin | Undecaprenyl pyrophosphate |
Inhibitors of Bacterial Cell Membrane: Colistin
⌄Colistin (Polymyxin E)
Bacillus polymyxa produces the polycationic peptide antibiotic known as colistin (Polymyxin E), which was identified in Japan in 1949. The source describes colistin as bactericidal through effective solubilization of the bacterial cell membrane.
Of the five chemical compounds in the polymyxin group—polymyxins A, B, C, D, and E—the source states that two are used clinically: colistin (polymyxin E) and polymyxin B.
The source describes colistin as a last line of defense against infections caused by multidrug-resistant Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenemase-producing Enterobacterales.
Resistance to Colistin
Resistance can occur through several processes. The supplied content states that until 2015 it was thought to be solely inherited by point mutations in the chromosome. Because LPS is the target of colistin, changes in LPS can alter colistin activity.
Salmonella and Escherichia coli can change LPS by converting lipid A into 4-amino-4-deoxy-L-arabinose (L-Ara4N) and/or phosphoethanolamine (PEtn). Its production is associated with chromosomal-mediated resistance and requires two-component response regulators PhoP/PhoQ and sensor kinase systems PmrA/PmrB [6–8].
Other Antimicrobial Groups
⌄Other antibacterial agents
- Inhibitors of bacterial protein synthesis
- Inhibitors of nucleic acid synthesis
- Other antibacterial agents
Antifungal agents
Listed as a major antimicrobial group in the supplied source; specific agents and mechanisms are not developed in the provided text.
Antiviral agents
| Category listed in source |
|---|
| Nucleoside analogue |
| Non-nucleoside analogue |
| Inhibitors of viral uncoating |
| Neuraminidase inhibitors |
| Interferons |
| Nucleoside and nucleotide reverse transcriptase inhibitors |
| Non-nucleoside reverse transcriptase inhibitors |
Antiparasitic agents
Listed as a major antimicrobial group in the supplied source; specific agents and mechanisms are not developed in the provided text.
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