A copper bullet for tuberculosis

October 03, 2018

Tuberculosis is a sneaky disease. The bacteria hide from antibiotics inside the very immune cells that are supposed to kill them, making treatment long and difficult. But in the November issue of ACS Infectious Diseases, UConn chemists report a new antibiotic that can find and kill tuberculosis bacteria where they hide.

Tuberculosis is the number one cause of death from infectious disease worldwide. About 25 percent of people on the planet are currently infected. Most of those infections will stay dormant, but one in 10 will become active, infectious, and often fatal if untreated.

Tuberculosis is caused by a bacteria called Mycobacterium tuberculosis. Because of Mycobacterium's unique lifestyle, in which they allow themselves to be eaten by macrophage immune cells and then grow inside of them, they are very hard to treat. People infected with tuberculosis must typically take a cocktail of antibiotics diligently over many months, because the bacteria are only susceptible to the drugs when they break out of the macrophage in which they were born and search out a new one to invade.

UConn chemist Alfredo Angeles-Boza and his then-graduate student, Daben Libardo, and colleagues from the Indian Institute of Science, the Max Planck Institute, and MIT, decided to make an antibiotic that could make its way into the macrophages and hit the Mycobacteria where they hide. Angeles-Boza and Libardo had previously worked with antibiotics produced by fish, sea squirts, and other sea creatures. Many of these sea creatures make antibiotic peptides - small pieces of protein-like material - with a special chemical talent: when they bind to copper atoms, they enable the copper to shift its electrical charge from +2 to +3 and back. Copper with this ability becomes aggressive, ripping electrons away from some molecules and adding them to others, particularly oxygen-containing molecules. The oxygen-containing molecules become free radicals, dangerous chemicals that attack anything they encounter, including Mycobacteria.

Human macrophages infected with Mycobacteria also use copper to attack the bacteria, but they do so in a less sophisticated way. They trap the bacteria in a bubble and then inject copper +1 ions - that is, plain copper atoms with a plus one charge (Cu+) - into the bubble. But the Mycobacteria can handle that. To them, the bubble is a safe haven, and the Cu+ ions are mere annoyances. The bacteria can steal an extra electron from the Cu+ to make it Cu2+. The copper becomes unreactive and safe that way. And when enough Cu2+ surrounds the Mycobacteria, other, more dangerous kinds of copper can't get close.

Surrounded by defanged copper, "the bacteria can grow in peace. It's elegant!" says Angeles-Boza. But if Angeles-Boza and Libardo have their way, the copper camouflage will become Mycobacteria's downfall. If the antibiotic peptides can get close to the bacteria, they can grab onto one of the copper ions and weaponize it. The trick is getting the peptide close to the bacteria.

To do that, the chemists put the peptides into little bubbles similar to the kind cells use to move around packets of protein ingredients and other tasty stuff. When the bacteria snags one for a snack, the peptide works its chemistry and kills it.

The antibiotic peptide developed by Libardo and Angeles Boza effectively kills Mycobacteria living in macrophages in the lab, but they haven't been able to cure tuberculosis in mice yet - peptide drugs have various problems that make them tricky to use in mammals. The next step in the research is to use the same chemistry in smaller molecules that can be taken as pills like more typical antibiotics.
This research was funded by grants from NSF.

University of Connecticut

Related Bacteria Articles from Brightsurf:

Siblings can also differ from one another in bacteria
A research team from the University of Tübingen and the German Center for Infection Research (DZIF) is investigating how pathogens influence the immune response of their host with genetic variation.

How bacteria fertilize soya
Soya and clover have their very own fertiliser factories in their roots, where bacteria manufacture ammonium, which is crucial for plant growth.

Bacteria might help other bacteria to tolerate antibiotics better
A new paper by the Dynamical Systems Biology lab at UPF shows that the response by bacteria to antibiotics may depend on other species of bacteria they live with, in such a way that some bacteria may make others more tolerant to antibiotics.

Two-faced bacteria
The gut microbiome, which is a collection of numerous beneficial bacteria species, is key to our overall well-being and good health.

Microcensus in bacteria
Bacillus subtilis can determine proportions of different groups within a mixed population.

Right beneath the skin we all have the same bacteria
In the dermis skin layer, the same bacteria are found across age and gender.

Bacteria must be 'stressed out' to divide
Bacterial cell division is controlled by both enzymatic activity and mechanical forces, which work together to control its timing and location, a new study from EPFL finds.

How bees live with bacteria
More than 90 percent of all bee species are not organized in colonies, but fight their way through life alone.

The bacteria building your baby
Australian researchers have laid to rest a longstanding controversy: is the womb sterile?

Hopping bacteria
Scientists have long known that key models of bacterial movement in real-world conditions are flawed.

Read More: Bacteria News and Bacteria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.