Defiant Bacteria Resisting `Trojan Horse` Antibiotic, Exposed

The mechanism by which certain bacteria elude a potent antibiotic was discovered by Indian origin scientists.

The researchers found that the bacteria have modified a common "housekeeping" enzyme in a way that enables the enzyme to recognize and disarm the antibiotic.

Trojan Horse Tactics to Infect Healthy Cells Observed in Chlamydia Bacteria
A novel mechanism has been identified in which Chlamydia trachomatis tricks host cells into taking up the bacteria.

Bacteria often engage in chemical warfare with one another, and many antibiotics used in medicine are modelled on the weapons they produce. But microbes also must protect themselves from their own toxins. The defences they employ for protection can be acquired by other species, leading to antibiotic resistance.

The researchers focused on an enzyme, known as MccF, that they knew could disable a potent "Trojan horse" antibiotic that sneaks into cells disguised as a tasty protein meal. The bacterial antibiotic, called microcin C7 (McC7) is similar to a class of drugs used to treat bacterial infections of the skin.

"How Trojan horse antibiotics work is that the antibiotic portion is coupled to something that's fairly innocuous - in this case it's a peptide. So susceptible bacteria see this peptide, think of it as food and internalize it," said University of Illinois biochemistry professor Satish Nair, who led the study.

Imaging of Diseased Cells to be Aided by Sleeping Trojan Horse
Researchers at Cardiff University have developed a unique strategy that is opening up new possibilities for improving medical imaging.

The meal comes at a price, however: Once the bacterial enzymes chew up the amino acid disguise, the liberated antibiotic is free to attack a key component of protein synthesis in the bacterium, Nair explained.

"That is why the organisms that make this thing have to protect themselves," he said.

Nano-sized 'Trojan Horse' Particle to Aid Nutrition Unveiled
Monash University researchers say that they have designed a nano-sized trojan horse particle that protects antioxidants from being destroyed in the gut, and ensures a better chance

In previous studies, researchers had found the genes that protect some bacteria from this class of antibiotic toxins, but they didn't know how they worked. These genes code for peptidases, which normally chew up proteins (polypeptides) and lack the ability to recognize anything else.

Before the new study, "it wasn't clear how a peptidase could destroy an antibiotic," Nair said.

Secret of Trojan Horse Viral Gene Revealed
Melbourne researchers have uncovered the secret behind the disguise of some viruses that manage to dodge detection by the body's immune system

To get a fuller picture of the structure of the peptidase, Illinois graduate student Vinayak Agarwal crystallized MccF while it was bound to other molecules, including the antibiotic.

An analysis of the structure and its interaction with the antibiotic revealed that MccF looked a lot like other enzymes in its family, but with a twist - or, rather, a loop. Somehow MccF has picked up an additional loop of amino acids that it uses to recognize the antibiotic, rendering it ineffective.

"Now we know that specific amino acid residues in this loop are responsible for making this from a normal housekeeping gene into something that's capable of degrading this class of antibiotics," Nair stated.

With this information, researchers - and eventually, doctors and other clinicians - will be able to scan the genomes of disease-causing bacteria to find out which ones have genes with the antibiotic-resistance loop in them, Nair said.

"If we know what type of bacteria are causing an infection we know what kind of antibiotic to give and what kind not to give," he noted.

The finding was reported in the Proceedings of the National Academy of Sciences.

Source-ANI