What Resistance Mechanisms Have Microbes Developed Towards Antibiotics?

Jeff Boyd, PhD, assistant professor of Biochemistry and Microbiology at Rutgers University School of Environmental and Biological Sciences, explains how Staphylococcus aureus and other microbes become antibiotic-resistant.

Interview Transcript (slightly modified for readability)

“Staphylococcus aureus, and many microbes in general, can acquire resistance a number of ways. First off, I should state that they could either be acquired resistances, so they can acquire genes from the environment or from other microbes which provide a mechanism to make that antibiotic inactive, or inaccessible to its target. The second thing they can do is just naturally you can have a selective pressure on the microorganism where it will get a mutation in its own DNA, which then disallows that antibiotic from working.

In the case of methicillin-resistant Staph aureus, the antibiotic methicillin is a beta-lactam antibiotic. Staphylococcus aureus can acquire a gene which disallows that antibiotic from interacting with the protein that is necessary to build a cell wall, [which is] an essential protein; so if you don’t have that protein, or that protein becomes inactive, the cell will die.

Another mechanism that microbes have is that they can actually cleave or inactivate an antimicrobial. By doing that [the microbe] disallows [the antimicrobial] from interacting with its environment as well.

Another mechanism [is that] microbes could acquire genes that encode for pumps. Inside the cytosol, inside the bacterial cell itself, if the antibiotic gets in, these mechanisms, or these genes, will encode for proteins which would pump that antibiotic back outside the cell, physically separating that antimicrobial agent from its target.

An additional mechanism that might be involved is a global metabolic rearrangement. [The microbe] could acquire a new metabolic pathway, which is no longer affected by that antimicrobial target. Or [the microbe] could even have a mutation in the organism’s DNA, [causing] a global metabolic rearrangement. An example of this would be certain microbial species, or you can select for what are called “small colony variance.” These microorganisms have a mutation in their DNA, which disallows them from using oxygen [to breathe]. So organisms can still live, they can still ferment, they grow very slowly, but they’re no longer able to actually transport those antimicrobials into the cell; it’s a physical process where they actually would use the energy that’s generated from breathing oxygen to transport that antimicrobial into the cell. So if the organism gets a mutation that no longer allows it to breathe oxygen, it doesn’t have the energy to transfer those antimicrobials into the cell, and hence the microbes become resistant to numerous antimicrobials.”