Mechanisms of antibiotic resistance

Bacteria have many different ways of becoming resistant to antibiotics including:

• Enzyme inactivation where the bacteria produce enzymes that can modify/destroy the antibiotic making it ineffective.

• Target modification where the bacteria changes the target site for the antibiotic that prevents it from binding to the cell.

• Decreased permeability where the bacteria cell alters their cell membrane making the antibiotic less effective.

These are just a few ways that bacteria have evolved to be resistant to antibiotics. 

Building on these general strategies, some bacteria have developed highly specific resistance mechanisms in response to certain antibiotics.

Target Modification

One of the major mechanisms by which Clostridioides difficile resists antibiotic treatment is through the modification of drug target sites. For example, resistance to vancomycin is often mediated by the Van operon, including genes such as vanS and vanR, which detect the presence of the antibiotic and initiate changes to the bacterial cell wall's peptidoglycan precursors. These changes reduce the drug’s binding affinity, rendering it less effective or entirely ineffective (Wickramage, Spigaglia, & Sun, 2021) . The illustration below demonstrates how this resistance mechanism functions at the molecular level.

Enzyme Inactivation

According to Marciniak, Tyczewska, & Grzywacz, (2024), antibiotic resistance can occur when bacteria produce enzymes that modify or destroy antibiotics, rendering them ineffective. This mechanism is particularly concerning because it can confer resistance to a broad spectrum of antibiotics . For example, resistance to antibiotics like daptomycin, vancomycin, and linezolid has been observed in methicillin-resistant Staphylococcus aureus (MRSA) strains, highlighting the critical threat posed by enzyme inactivation  . The ability of bacteria to neutralize antibiotics through enzymatic action underscores the evolutionary arms race between antibiotic development and the emergence of resistance 

Decreased Permeability

Another mechanism of antibiotic resistance involves bacteria altering their cell membranes to reduce permeability, which decreases the effectiveness of antibiotics by limiting their ability to enter the cell . This adaptive change in the bacterial cell's structure prevents antibiotics from reaching their intracellular targets . Decreased permeability is one of several mechanisms, including drug alteration and efflux pumps, that Clostridioides difficile uses to resist a wide variety of antibiotics . Such alterations emphasize the sophistication of bacterial resistance mechanisms and the challenges they present to effective treatment (Wickramage, Spigaglia, & Sun, 2021) .