The path of least resistance

By | Science & Technology
Innoculated Petri dish. Credit@Bar-Ilan University

The first new antibiotic to be discovered in 30 years was recently unearthed by an international team of scientists. It has been named teixobactin. The team, led by Kim Lewis of Northeastern University, extracted the antibiotic from soil bacteria and has demonstrated its ability to fend off a wide spectrum of pathogenic bacteria. The findings are published in the weekly science journal, Nature.

Few classes of pharmaceutical agents have had such a profound impact on public health as antibiotics. Infectious pathogens were once the most common cause of mortality, however, largely due to antibiotics, this state has improved significantly.

While that may be, the spread of antibiotic resistance has become a global public health concern according to the World Health Organisation (WHO). This spotlight is pushing researchers to develop new, innovative methods to prevent the rise of resistance. One of the most common forms of drug resistant bacteria is the MRSA (methicillin-resistant Staphylococcus aureus) ‘superbug’.

Microbes cultured in Petri dishes. Credit@ PacificNorthwestNationalLaboratory-PNNL

Microbes cultured in Petri dishes. Credit@
PacificNorthwestNationalLaboratory-PNNL

Antibiotic resistance evolves when microorganisms survive exposure to antimicrobial agents. Before the widespread use of antibiotics, small levels of antibiotic resistant bacteria existed; many genes for resistance are ancient. When antibiotics are used, they rid the majority of the pathogenic bacteria. The small percentage that do survive harbour mutations, which were randomly acquired by chance, many years ago.

Additionally, some bacteria can horizontally transfer their resistance to other bacteria, passing the trait along. This minority of drug resistant bacteria then thrives and spreads to other patients. Likewise, greater use of antibiotics in hospitals over the past 50 years exerted a selective pressure on bacteria, favouring the survival of resistant strains. Many studies suggest a strong association between bacterial resistance and antibiotic prescription in the hospitals.

Now, health organisations may breathe a small sigh of relief. Teixobactin marks the beginning of a new era of antibiotics. The technology developed by the team might herald an entirely new class of antibiotics altogether. For the past century, screening bacteria and fungi from soil samples has revealed several new antibiotics. However, only a very small proportion of microbes found this way are cultivable under typical lab conditions.

The team’s solution to this challenge is a multichannel device called the iChip, which isolates and grows uncultured bacteria. Soil is first diluted and then poured onto the iChip, which has many tiny through-holes. The technique aims to place one microorganism in each hole. The plate is then dipped into molten agar that fills the holes, capturing the microbes as it cools and solidifies. The iChip is then placed in the soil from which the microbes originated, free to consume the nutrients it finds naturally without being contaminated by other species.

Photo of the iChip being used in soil. Credit@NicoleWilson

Photo of the iChip being used to extract microbes from the soil. Credit@NicoleWilson

Previously, only 1% of soil-mined bacteria may have been cultured in labs; this technique allows up to 75% of the iChip microbes to be transferred and grown under lab conditions. It is thought that the reason for this dramatic increase of capable bacteria might be to do with mutations acquired by bacteria during the process – although details remain unclear. Understanding this difference might allow scientists to rapidly develop new antibiotics.

Teixobactin is a cell wall inhibitor. It causes the breakdown of bacterial cells walls or prevents them from being synthesised. The antibiotic shows excellent potency versus most Gram-positive species of bacteria, with exceptional bactericidal activity towards S. aureus. Interestingly, teixobactin was shown to be even more potent than the existing antibiotic vancomycin at interrupting bacterial populations in the late phase of growth. This may be promising considering that the clinical failure in patients of MRSA treated with vancomycin is linked to its modest bactericidal activity.

Being an antibiotic, teixobactin remains susceptible to bacterial resistance. However, it took 30 years for bacteria to become resistant to vancomycin and scientists expect teixobactin resistance to take even longer to build up. Clinical trials are scheduled to start in two years.

This discovery has slowed microbial progress in the immunological arms race, allowing the human body to capitalise once again. Nevertheless, it is important to note that while new antibiotics may delay the inevitable spread of resistance, it might eventually still evolve in 20-30 years. Yet, it buys scientists a great deal of time to productively research more permanent solutions to the challenge.

How might treatment productively adapt to counteract the spread antibiotic resistance?

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