Halicin (SU-3327) is a

chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...

that acts as an inhibitor of the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

c-Jun N-terminal kinase c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and are ...

(JNK). Originally, it was researched for the treatment of

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

, but development was discontinued for this application due to poor results in testing.

Naming

Researchers named the molecule after the fictional

artificial intelligence Artificial intelligence (AI) is intelligence—perceiving, synthesizing, and inferring information—demonstrated by machines, as opposed to intelligence displayed by animals and humans. Example tasks in which this is done include speech re ...

system from '' 2001: A Space Odyssey'' because of how AI predictive computer models were used to identify the probability it would work as an antibiotic.

Antibiotic ability

Halicin was identified by artificial intelligence researchers at the

MIT Jameel Clinic The MIT Abdul Latif Jameel Clinic for Machine Learning in Health (commonly, MIT Jameel Clinic; previously, J-Clinic) is a research center at the Massachusetts Institute of Technology (MIT) in the field of artificial intelligence (AI) and health sc ...

in 2019 using an ''

in silico In biology and other experimental sciences, an ''in silico'' experiment is one performed on computer or via computer simulation. The phrase is pseudo-Latin for 'in silicon' (correct la, in silicio), referring to silicon in computer chips. It ...

deep learning Deep learning (also known as deep structured learning) is part of a broader family of machine learning methods based on artificial neural networks with representation learning. Learning can be supervised, semi-supervised or unsupervised. De ...

approach, as a likely broad-spectrum

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

. This likelihood was verified by ''in vitro'' cell culture testing, followed by ''in vivo'' tests in mice. It showed activity against drug-resistant strains of '' Clostridiodes difficile'', ''

Acinetobacter baumannii ''Acinetobacter baumannii'' is a typically short, almost round, rod-shaped ( coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromi ...

'', and ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...

'', with an unusual mechanism of action involving the sequestration of

iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...

inside the bacterial cells, that thereby interferes with their ability to regulate the pH balance across the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

properly. Since this is a different mode of action from most antibiotics, halicin retained activity against bacterial strains resistant to many commonly used drugs. Preliminary studies suggest that halicin kills bacteria by disrupting their ability to maintain an electrochemical gradient across their cell membranes. This gradient is necessary, among other functions, to produce ATP (molecules that cells use to store and transfer energy), so if the gradient breaks down, the cells die. This type of killing mechanism could be difficult for bacteria to develop resistance to.

References

External links

Machine Learning for Antibiotics
Enzyme inhibitors Antibiotics {{antiinfective-drug-stub