The Mechanism of Antimicrobials in Fighting Infections

In the complex interaction between pathogens and the human body, antimicrobials are vital in the fight against infection. Understanding the mechanisms by which these agents combat pathogens is crucial for realising their efficacy so, how do antimicrobials work? In this blog post, we will look at the intricate mechanisms of antimicrobials with references to established research in the field.

Antibiotics

The majority of antimicrobials fall under the category of antibiotics, designed to combat bacterial infections. Antibiotics exert their antimicrobial effects through various mechanisms, including inhibition of bacterial cell wall synthesis, disruption of protein synthesis, interference with nucleic acid metabolism, and inhibition of essential metabolic pathways:

1. Inhibition of cell wall synthesis: Beta-lactam antibiotics, such as penicillin’s and cephalosporins, inhibit the formation of bacterial cell walls by targeting enzymes like penicillin-binding proteins (PBPs) (1).
2. Disruption of protein synthesis: Aminoglycosides, such as gentamicin, interfere with bacterial protein synthesis by binding to the bacterial ribosome (2).
3. Inhibition of nucleic acid metabolism: Quinolone antibiotics, like ciprofloxacin, target bacterial DNA gyrase and topoisomerase IV, disrupting DNA replication and repair processes (3).

Antivirals

Antiviral agents play a crucial role in combatting viral infections by inhibiting viral replication at various stages of the viral life cycle. For example:

1. Nucleoside analogs, like acyclovir, interfere with viral DNA synthesis and halt viral replication (4).
2. Protease inhibitors, such as ritonavir, block the activity of viral proteases, preventing the maturation of viral proteins and the release of mature viral particles (5).

Antifungals

Fungal infections are combated by antifungal agents that target essential components of fungal cells. Azoles, for example, interfere with fungal cell membrane synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase (6).

Antiparasitics

Antiparasitic agents exhibit diverse mechanisms of action to combat a range of parasitic infections:

1. Artemisinin derivatives, like artemether, target the mitochondria of Plasmodium parasites, disrupting their electron transport chain and causing oxidative damage (7,8).
2. Ivermectin, used against helminthic infections, binds to glutamate-gated chloride channels in parasitic organisms, leading to paralysis and death of the parasites (9).

Conclusion

The mechanisms of antimicrobials are diverse and complex – from bacterial cell wall synthesis to viral replication and parasitic metabolism, these agents use a number of intricate mechanisms to combat infections. The understanding of these antimicrobial mechanisms allows us insight into how we can continue to innovate and through ongoing research, we can ensure the sustained effectiveness of antimicrobials in improving standards of human health.

References:

1. Bush K, Bradford PA (2016) β-Lactams and β-Lactamase Inhibitors: An Overview, Cold Spring Harb Perspect Med: 6 (8)
2. Javier Aguirre Rivera JA et al. (2021) Real-time measurements of aminoglycoside effects on protein synthesis in live cells. PNAS: 118 (9) e2013315118.
3. Pham TDM et al. (2019) Quinolone antibiotics. Med. Chem. Commun: 10, 1719-1739
4. Zenchenko AA et al. (2021) Antiviral and Antimicrobial Nucleoside Derivatives: Structural Features and Mechanisms of Action. Mol Biol: 55(6): 786-812.
5. Majerová T et al. (2022) Viral proteases as therapeutic targets. Mol Aspects Med: 88:101159.
6. Kane A et al. (2022) Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox. Pharmaceuticals: 15(4):482.
7. Laleve A et al. (2020) Artemisinin and its derivatives target mitochondrial c-type cytochromes in yeast and human cells. Molecular Cell Research: 1867(5)
8. Mohamed E.M et al. (2016) Antischistosomal activity of artemisinin derivatives in vivo and in patients. Pharmacological Research: 110, 216-226.
9. Atif M et al. (2017) Effects of glutamate and ivermectin on single glutamate-gated chloride channels of the parasitic nematode H. contortus. PLoS Pathog: 13(10):e1006663.