A Trojan Horse For Killing Drug-Resistant Microbes

By hijacking the heme acquisition system of bacteria, researchers in Japan have devised a method to kill microbes that are resistant to antibiotic treatment.

AsianScientist (Oct. 9, 2019) – Like the mythical Trojan Horse that spelt the downfall of the city of Troy, a compound developed by researchers in Japan slips into bacteria via the microbes’ heme acquisition system to wreak havoc on metabolism. The findings are reported 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, and severe infections can be deadly.

To acquire difficult-to-access iron from the human body, P. aeruginosa secrete a protein called HasA to latch on to heme in the blood. The resultant complex is then recognized by a membrane receptor on the bacterium called HasR, permitting heme entry into the bacterial cell. Thereafter, HasA is recycled to pick up more heme.

In this study, Assistant Professor Osami Shoji of Nagoya University, Japan, and his team have found a way to hijack this heme acquisition system for drug delivery. They developed a powdered 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,” said Shoji.

When tested, over 99.99 percent of the bacteria were killed following treatment with one micromolar of HasA with GaPc, followed by exposure to ten minutes of irradiation. The strategy also worked on other bacteria with the HasR receptor on their membranes, but not on those without it.

The heme acquisition system is so essential to the survival of P. aeruginosa that it is unlikely the bacteria will develop resistance to the HasA-GaPc treatment strategy, said the researchers.

“Our findings support the use of artificial heme proteins as a Trojan horse to selectively deliver antimicrobials to target bacteria, enabling their specific and effective sterilization, irrespective of antibiotic resistance,” said Shoji.

The article can be found at: Shisaka et al. (2019) Hijacking the Heme Acquisition System of Pseudomonas aeruginosa for the Delivery of Phthalocyanine as an Antimicrobial.


Source: Nagoya University; Photo: Osami Shoji.
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