Ask the microbiologist Dra. Jessica Sheldon (PhD). (Photo: Submitted)
When this type of antibiotic-resistant bacteria infects a host, the host responds by starving the bug of metals, nutrients essential to the bacteria’s survival. These are the first salvos in a growing battle to infect or defend the host, according to research recently published in PLOS Pathogens.
“As with all life forms, microbes require nutrient metals for their survival and growth,” said Dr. Jessica Sheldon (PhD), a microbiologist at the USask School of Medicine and lead author of the study. “Limiting access to these metals is one method the host can use to control infection.”
In 2017, the World Health Organization named multidrug resistant A. baumannii at No. 1 on its list of “priority pathogens,” a catalog of bacteria that pose the greatest threat to human health and that urgently require research and development of new therapeutic approaches.
According to research by the Canadian Nosocomial Infection Surveillance Program, the incidence rate of A. baumanniiin Canada is low: only 0.015 cases per 1,000 hospital admissions, but per 100 people infected with A. baumanniinearly a quarter will die as a result.
Where some bacteria depend on toxins, A. baumannii The strength of ‘s lies in its ability to adapt to harsh environments: drying, disinfection and exposure to highly acidic or basic conditions cause the bacteria to produce a biofilm. Like tin broom or dental plaque, these biofilms allow the pathogen to adhere to surfaces and survive and thrive in hospital environments until a suitable host is found.
But the acquisition of metals such as iron, zinc and manganese is key to knowing how harmful A. baumannii can become When bacteria are mutated or altered in the ability to acquire metals, the results of infection are often much less severe.
“Iron plays a particularly important role A. baumannii infection,” Sheldon said.
In vitro and in a mouse model, the researchers identified that a particular host-produced protein, lipocalin-2, is essential in controlling disease severity. Production of the protein restricts the amount of iron the bacteria obtain, reducing the likelihood that the host will die from a blood infection and inhibiting the growth of the bacteria in the infected lungs.
The pathogen, in turn, sets in motion several countermeasures that allow it to acquire iron.
“During this ‘battle for the metals’, A. baumannii it produces small iron-binding molecules,” Sheldon said. “These molecules are able to bind iron so tightly that they can struggle to pull it away from the host’s proteins and then return it to the bacteria. Lipocalin-2, in turn, can sequester some of these molecules, rendering them ineffective and setting up an evolutionary arms race between host and pathogen over the metal.”
“To develop new drugs or strategies to treat infections, we need to have a better idea of how the host resists infection and how the bacterium overcomes that resistance,” Sheldon said. “Our data suggest that therapeutics that enhance the host’s ability to restrict iron availability … may represent viable avenues for drug development.”
A. baumannii it causes devastating infections, such as sepsis and ventilator-associated pneumonia. The outbreaks have been associated with the ongoing COVID-19 pandemic, causing infections in critically ill and ventilated patients.
“Once it gets into a hospital setting, it can be extremely difficult to get rid of it,” Sheldon said.
The next steps in the research involve a collaboration with Dr. Ninad Mehta (PhD) at the Royal University Hospital in Saskatoon to determine whether A. baumanniifound here differs genetically from bacteria found around the world. The results may provide clues as to why the pathogen is less common in Canada than elsewhere.
The research was completed while Sheldon was completing a postdoctoral fellowship at Vanderbilt University Medical Center in Nashville, Tennessee, supervised by Dr. Eric Skaar (PhD), and working with Drs. Lauren Himmel (DVM, PhD), Dillon Kunkle (PhD), Andrew Monteith (PhD) and research specialist Nichole Maloney, and funded by the Canadian Institutes of Health Research and the National Institutes of Health.