I’m not sure if many of you have been outsmarted by a singular cellular organism, but a team of scientists led by Erdal Toprak and Adrian Veres at Harvard University are trying to understand the evolution of bacteria to stop them mutating and outsmarting their drug treatment.
Evolution, a theory developed by Charles Darwin, suggests that we have been evolving for the past 65 million years through a process called natural selection. This process creates and preserves traits that are better for survival and reproduction, allowing a species to adapt to its environment. Natural selection is not the only known cause of evolution. Mutations, which are changes in the DNA sequence of a cell’s genome, are also a major factor.
Understanding evolution may help us understand how microbes develop resistance to drug treatment. Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial in curing a disease. An antimicrobial can be an antibiotic, antiparasitic or an antiviral.
Bacteria can evolve in less than 10 days due to their short generation times and large population sizes. If a bacterium gets a resistance gene stuck into its DNA, all of its progeny (offspring) will inherit the gene. Due to natural selection, bacteria with these genes survive and outgrow susceptible variants.
Mutations in the genome of bacteria can cause it to develop resistance to antibiotics by becoming less permeable, for example. If the antibiotic manages to enter the bacterial cell, some act like unfriendly club bouncers that kick the antibiotic out the back door.
To see how bacteria mutates, the team at Harvard developed a ‘’morbidosat’’, a device that constantly monitors the growth of bacteria and dynamically regulates antibiotic concentration. They investigated how Escherichia coli responds to three different antibiotics; chloramphenicol, doxycycline and trimethoprim over 25 days. Increased resistance occurred for all drugs, however, changes were observed in different areas of the genome. These results show that by being able to locate mutations on the genome of bacteria, further research can be conducted in designing drugs to switch these mutations off, minimising resistance. Much more research needs to be conducted as E. Coli is just one species of bacteria out of millions with billions of possible mutations.
A poorly treated bacterial infection can cause resistance. This could be due to not finishing the antibiotic prescription, allowing the remaining bacteria, which was less susceptible to the drug, to survive and reproduce.
Bacteria are not the only biological tricksters. Drug resistant viruses like influenza and parasites are becoming a larger threat in developing countries.
Malaria is a mosquito- borne infectious disease caused by the protozoan parasite Plasmodium falciparum. Once in the body, the malaria parasite multiplies and invades our red blood cells. Infection with P. falciparum, if not promptly treated, may cause kidney failure, seizures, mental confusion, coma, and death.
Chloroquine, an anti-malarial drug, is affordable, accessible, with low toxicity making it easy to distribute in poor regions. Research published by David J. Johnson et al, of the Liverpool School of Tropical Medicine in 2004 showed how a protein called PfCRT inside the parasite had enabled it to become resistant to chloroquine by creating a ‘back door’ and sneaking the drug out of the parasite by leakage. This is a very similar mechanism to the ‘bouncers’ in drug resistant bacteria.
Resistance is caused by poor drug administration programmes such as giving doses that are too low to kill the parasite, and like with bacteria, it follows with the evolution of strains of malaria parasites which are firmly resistant to that drug.
Artemisinin-based combination therapies (ACTs) were adopted. However, in 2006, a growing number of cases of malaria resistant to Artemisinin combination treatment were reported in Cambodia and now this resistant strain has spread to Thailand and neighbouring countries. Tim Anderson of the Texas Biomedical Research Institutes predicts that mortality figures will rebound if the drug loses its efficacy. “We are seeing that the drug kills the parasite less well than it used to. That doesn’t mean that the parasites are not killed, so we can still cure patients. But the concern is that the number of patients who are NOT cured will rise.’’ A team led by Aung Pyae Phyo MD, of Mahidol University, Bangkok, Thailand measured how long it takes for the number of malaria parasites in a person’s blood to halve in 3,200 patients from clinics on Thailand’s western border. With artemisinin treatment, this should take around 2 hours. In Cambodia, it now takes around 5.5 hours.
Isolating genes in the malaria parasite will help researchers understand how they have evolved to become resistant.
Instead of constantly developing new expensive drugs to combat these infectious diseases, scientists are looking into how mutations on the genome of a microbe during its evolution can cause resistance. From this, drugs that stop these mutations can be taken in conjunction of the treatment allowing the antibiotic or anti-malarial do its job.