A hope to fight antibiotic-resistant infections

January 12, 2015 , Anton Nikolaev

A new study published in Nature this week describes a new class of antibiotics that bacteria are not yet resistant to. This is an important break-through because the last class of antibiotics was found nearly 30 years ago. How do antibiotics work? How do bacteria acquire resistance to antibiotics?

Antibiotics are chemical compounds killing or slowing down the growth of bacterial cells. The first antibiotic, ampicillin, was discovered by Alexander Fleming and purified for medical purposes by Howard Florey’s team in 1940s:

Molecule of ampicillin

Since then, many lethal infections, such as pneumonia, cholera, tuberculosis and meningitis could be cured. However, the bacterial empire strikes back and many microorganisms are now developing resistance to common antibiotics used in in clinical practice. This is one of the biggest medical problems: in USA alone, more than 20 000 people die from infections caused by antibiotic-resistant bacteria each year. How do antibiotics work and what makes bacteria resistant?

Modes of antibiotic action

Antibiotics attack structures or molecules that are different in humans and microorganisms. Most common target of antibiotics is cell wall. In addition to cell membrane, bacteria have a stiff wall serving to protect them from destruction caused by internal pressure. It is made of chains of carbohydrates linked together by short peptides.

Bacteria cell wall vs human cell membrane

Many antibiotics, such as ampicillin, block the activity of enzymes needed for cell wall formation. Because human cells do not have cell walls, the antibiotics do not affect them.

Mechanisms of anibiotic resistance

Living organisms adapt to the environment and it is no surprise that bacteria started to develop resistance to antibiotics. To understand the mechanisms of antibiotic resistance, let us go back to ampicillin. As we described above, it prevents the formation of the cell wall. This usually kills bacteria but some species have a protein that breaks down ampicillin and other antibiotics having similar chemical structure. This protein, called beta-lactamase, is what makes bacteria resistant. It turned out that bacteria could transfer beta-lactamase gene to another bacteria. How does this happen?

In addition to chromosomal DNA, bacteria can possess small circular DNA molecules carrying several genes and sequences allowing them to be transferred from one cell to another. This transfer happens when two different cells, not necessarily belonging to the same species, come close to each other and form a bridge through which these circular DNAs diffuse to another cell. This mechanism, along with others, allows bacteria to acquire resistance to antibiotics.

Find out more about other mechanisms of antibiotic resistance in this movie:

What did the new study do to deal with antibiotic resistance?

The scientists discovered a new type of antibiotic that bacteria are not yet resistant to. This is an important break-through because the last class of antibiotics was found nearly 30 years ago. The difficulty to discover new classes comes from the fact that most of the antibiotics were extracted from microorganisms living in soil. However, only a small fraction (around 1%) of soil microorganisms could have been cultured in laboratory conditions. To overcome this problem, Losee Ling and colleagues applied technology, allowing cultivating many more types of soil bacteria directly in their natural environment. Using this technology they extracted new potential antibiotic, which they termed teixobactin. It was tested on mice and turned out to be non-harmful to mammalian cells. Teixobactin acts by inhibiting cell wall synthesis.