Mechanisms of Antimicrobial Resistance

Mechanism of antimicrobial resistance is a naturally occurring process, which makes common infections harder to treat. Microbes constantly evolve and evade anything that exerts selective pressure on them, including antimicrobials. This means that even non-harmful microbes can develop resistance mechanisms. Antimicrobial resistance refers to the loss of sensitivity in microbes to antimicrobial agents. These are often designed to either inhibit their growth or kill them. Antimicrobial resistance includes resistance across all the microbes, including bacteria, viruses, protozoa, and fungi. Understanding the mechanisms behind resistance can help slow the spread of resistant infections.

How antimicrobials work

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The term "antimicrobials" directly pinpoints a chemical substance, produced or derived from a microorganisms, that can kill or inhibit the microbial growth. One of such are antibiotics. Antibiotics work in two different ways. They can either have bactericidal action, which directly kills bacteria. Or they can have bacteriostatic action, which stoops bacterial growth, allowing the immune system to get rid of the infection.

Antibiotics do not have the same effect in viruses and fungi as they have different biological structures and mechanisms than bacteria. As such, there are fewer antiviral and antifungal drugs. Viruses and fungi grow and function in different ways than bacteria. Viruses replicate by hijacking host cells, while fungi have complex cellular structures that are resistant to many antibiotics. Therefore, the number of antiviral and antifungal treatments is much more limited. On top of that, these treatments are often less effective than antibiotics for bacterial infection.

Antibiotic mechanisms

Antibiotics are chemical substances that can be either produced or derived from microorganisms that can kill microbes or inhibit their growth. The agents are used in treating bacterial infections and function in two primary ways:

1. Inhibiting bacterial reproduction by preventing them from multiplying. The process includes the disruption of essential processes such as DNA replication, protein synthesis, or cell wall formation. This keeps the number of bacteria under control and allows the immune system to eliminate the remainder.
2. Killing bacteria by targeting key cellular components, which results in directly eliminating the infection. Some of the agents disrupt the cell wall of the bacteria, resulting in the rupture of the cell. Others affect the essential enzyme functions, which makes the bacteria unsuitable for survival.

Mechanisms of antimicrobial resistance

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Mechanisms of resistance include acquired characteristics that allow microbes to avoid the effects of the agents, resulting in less effective treatments. The main antimicrobial resistance mechanisms include:

Enzymatic Drug Inactivation

Some bacteria produce enzymes that break down or modify antimicrobial agents. This makes them ineffective. Some of these include beta-lactamase and aminoglycoside-modifying enzymes. While beta-lactamase destroy the beta-lactam type of antibiotics such as penicillin; aminoglycoside-modifying enzymes chemically change aminoglycoside antibiotics, which directly prevents their action.

Target modification

Bacteria have the ability to alter the molecular composition of antimicrobial drugs. This results in reduced drug binding and effectiveness. One of such modifications is the alteration of penicillin-binding proteins. Another includes the mutations in ribosomal RNA, which prevents macrolide and tetracycline antibiotics from binding to the target.

Efflux pumps

Some microbes adapt efflux pumps, which are special proteins that actively transport the antimicrobial agent out of the cell. This process reduces the intracellular concentration resulting in prolonged survival of the microbe. It is commonly found in gram-negative bacteria, which use it to expel antibiotics.

Reduced drug uptake

Microbes can gain the ability to change their outer membrane or cell wall. This prevents the antimicrobial agents from entering. There are two ways through which the reduced drug uptake can be achieved: loss or alteration of porins and thickening of the cell wall.

Genetic pathways of resistance

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The mechanisms of antimicrobial resistance include various genetic changes, which result in the change of the microbial cell properties. These allow them to withstand the effects of antimicrobial agents. The two main genetic pathways include:

Mutation

Genetic mutations occur spontaneously during microbial cell division. They can lead to alterations in targeting proteins, reducing drug binding or modifying metabolic pathways to avoid the effects of antimicrobial agents. Out of the microbes, bacteria are especially prone to genetic mutations due to their single-chromosome structure and high replication rate.

Genetic exchange

Bacteria can acquire resistance genes through genetic exchange. These mechanisms include transduction and conjugation. During transduction, a bacterial virus (bacteriophage) transfers DNA from one bacterium to another. This introduces new resistance genes and alters the genetic composition. On the other hand, conjugation involves direct transfer of plasmids. Plasmids are small and mobile fragments of DNA. These are transferred between bacteria and often carry resistance genes that are involved in drug-inactivation or efflux pumps. During conjugation, resistance can spread rapidly, as plasmids can be shared between different bacterial species.

Types of antimicrobial resistance

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There are three different types of antimicrobial resistance, differentiated based on the way they occur. Biological resistance occurs when microbes develop reduced sensitivity to antimicrobial agents. This type of resistance results from an evolutionary shift which may or may not result in treatment failure. On the other hand, clinical resistance occurs when the microbes is so resistant to the agent that the treatment fails.

Another type of resistance is called intrinsic resistance. This type occurs naturally and results in microbes resisting specific types of antimicrobials through inherent structural or functional characteristics. This include the lack of binding between the drug and the microbe as well as the inability for the drug to enter the cells. Another process includes the natural efflux mechanism, which expels the antimicrobial agent before it has the chance to take effect.

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