Bacterial Resistance to Antibiotics – How does it Occur?

Although the emergence of bacterial antibiotic resistance has concerned those involved in public health for many years, the mechanism for this resistance is still poorly understood.  The magnitude of this problem is compounded by the global spread of the infectious agents that cause such diseases as gonorrhea and tuberculosis and that have become resistance to a broad spectrum of antibiotics.

Dr. Qiucen Zhang from the Department of Physics at Princeton University in a collaborative effort with others at various institutions has attempted to define the variables and quantify the nature of the development of bacterial immunity to antibiotics.

In previous work, resistant mutations in bacterial populations have been isolated and their genetic makeup successfully analyzed.  However, Zhang and his colleagues sought to understand how such mutations actually occur and spread within a given bacterial population when it is first subjected to antibiotics.

In order to elucidate this process, it was important to simulate the micro-environment that is present in nature – within a host organism, for example.  The candidate organism that was chosen for this study was Escherichia coli, a ubiquitous bacterial species.  A device was constructed for this purpose was designed to mimic a normal bacterial niche.  The antibiotic that was chosen for this study was ciprofloxacin, often used in a clinical setting.  This substance inhibits DNA replication and cell division but does not kill the bacterial cell target.

The findings from these experiments were that resistance of Escherichia coli to ciprofloxacin occurred within a mere ten hours of the introduction of the drug, and with as few as 100 bacteria.  In addition, DNA analysis of the resistant strain showed four unique single-nucleotide polymorphisms (SNPs) that could account for the antibiotic resistance.

These results are of immense importance in that they help elucidate the often rapid appearance of antibiotic resistance with the body of mammals, including humans.  These data may also be of used in improving the understanding of the emergence of drug resistance in patients undergoing cancer chemotherapy.