A solution of the extracellular heme acquisition system protein A (HasA) with gallium phthalocyanine (Left) and the results of sterilization of Pseudomonas aeruginosa and Escherichia coli treated with HasA-bound gallium phthalocyanine by irradiation with near-infrared light (Right). Credit: Osami Shoji
A new Trojan horse approach could lead to treatments for some antibiotic-resistant bacteria.
A deadly, antibiotic-resistant bacterium can be sterilized by hijacking its haem-acquisition system, which is essential for its survival. The new strategy, developed by Nagoya University researchers and colleagues in Japan, was published in the journal ACS Chemical Biology.
Pseudomonas aeruginosa is a dangerous bacterium that causes infections in hospital settings and in people with weakened immune systems. It can cause blood infections and pneumonia, while severe infections can be deadly. Highly resistant to antibiotic treatment, P. aeruginosa is one of the most critical pathogens urgently requiring alternative treatment strategies, according to the World Health Organization.
This bacterium is one of many that have evolved a system that allows them to acquire difficult-to-access iron from the human body. Iron is essential for bacterial growth and survival, but in humans, most of it is held up within the ‘haem’ complex of haemoglobin. To get hold of it, P. aeruginosa and other bacteria secrete a protein, called HasA, which latches onto haem in the blood. This complex is recognized by a membrane receptor on the bacterium called HasR, permitting haem entry into the bacterial cell, while HasA is recycled to pick up more haem.
Bioinorganic chemist Osami Shoji of Nagoya University and collaborators have found a way to hijack this ‘haem acquisition system’ for drug delivery. They developed a powder formed of HasA and the pigment gallium phthalocyanine (GaPc), which, when applied to a culture of P. aeruginosa, was consumed by the bacteria.
“When the pigment is exposed to near-infrared light, harmful reactive oxygen species are generated inside the bacterial cells,” explains Shoji. When tested, over 99.99% of the bacteria were killed following treatment with one micromolar of HasA with GaPc and ten minutes of irradiation.
The strategy also worked on other bacteria with the HasR receptor on their membranes, but not on ones without it.
The haem acquisition system is so essential to these bacteria’s survival that it is not expected to change, making it unlikely the bacteria will develop resistance to this drug strategy, the researchers believe.
“Our findings support the use of artificial haem proteins as a Trojan horse to selectively deliver antimicrobials to target bacteria, enabling their specific and effective sterilization, irrespective of antibiotic resistance,” the team reports in their study.
The researchers next aim to test their strategy for treating infections, and are working on modifying their approach for sterilizing other pathogens that possess a similar haem acquisition system.
Learn more: New strategy to kill pathogens resistant to antibiotics
The Latest on: Antibiotic resistance
via Google News
The Latest on: Antibiotic resistance
- As More Bacteria Grow Resistant to Antibiotics, Scientists Are Fighting Backon January 21, 2021 at 2:43 pm
USC experts search for answers to deadly superbugs and ways to keep them from spreading to you and the ones you love.
- The Pandemic Is Exacerbating Antibiotic Resistance, Says Concerned Wash U Physicianon January 21, 2021 at 2:24 pm
A study published in the peer-reviewed medical journal Clinical Infectious Diseases finds that in addition to up to half of adults being wrongfully prescribed antibiotics in hospital settings, one in ...
- Antibiotic resistance may spread even more easily than expectedon January 21, 2021 at 4:49 am
Pathogenic bacteria in humans are developing resistance to antibiotics much faster than expected. Now, computational research at Chalmers University of Technology, Sweden, shows that one reason could ...
- CBD Destroys Antibiotic-Resistant Bacteria Such as Gonorrhea, Study Findson January 21, 2021 at 12:30 am
For the first time ever, researchers at the University of Queensland have found how cannabis can provide a solution to antibiotic-resistant bacteria. A non-psychoactive cannabinoid known as ...
- Antibiotic resistance may be more widespread than previously expectedon January 20, 2021 at 11:40 pm
Pathogenic bacteria in humans are developing resistance to antibiotics much faster than expected. Now, computational research at Chalmers University of Technology, Sweden, shows that one reason could ...
- Overuse of antibiotics for meat production drives resistance in humanson January 20, 2021 at 8:05 pm
Mention antibiotic resistance and few people would link what is increasingly being recognised as a growing global health crisis with a Big Mac. But in the US, animals farmed for food account for most ...
- Origins of Antibiotic Resistanceon January 20, 2021 at 8:09 am
As the use of antibiotics increases, as does antibiotic resistance. It is vital to understand how antibiotic resistance has emerged and the ways to prevent it.
- CBD Kills Antibiotic-Resistant Bacteria Such As Gonorrhea, According To Studyon January 20, 2021 at 7:10 am
Antibiotic resistance currently poses a major threat to global healthcare systems, but a new study in the journal Nature Communications Biology suggests th ...
- Unlocking 'the shape of water' in mechanisms of antibiotic resistanceon January 19, 2021 at 5:57 pm
Researchers captured and comparted hi-res images of ribosome structures from sensitive and resistant bacteria and report that a water molecule needed for antibiotic binding was not present in the ...
- Oxford given £100m for antibiotic resistance researchon January 19, 2021 at 2:54 am
Britain's Oxford University has received a donation of £100 million (112 million euros, $136 million) to research growing resistance to antibiotics, the university announced on Tuesday.
via Bing News
