BEIJING, Jan. 12, 2023 /PRNewswire/ — Iron, a biologically important trace element, is necessary for the survival of various organisms including humans and bacteria. Iron plays a critical role in various physiological processes and its levels inside the human body are tightly regulated. Infecting bacteria must compete with humans for iron, and so have evolved various mechanisms for iron uptake. Meanwhile humans have also developed some mechanisms to resist this iron uptake by bacteria. A group of Chinese researchers have recently reviewed these mechanisms and outlined clinical strategies for safeguarding human health from bacterial infections. Their paper was published in Volume 136, Issue 16 of the Chinese Medical Journal on 20 August 2022.
Says corresponding author Dr. Ning Shen from Peking University Third Hospital, “The competition for iron leads to a war between humans and bacteria. To grow, reproduce, colonize, and successfully cause infection, bacteria need iron. Inside the human body, iron exists in the ferric (Fe3+) and ferrous (Fe2+) forms. So, these pathogens have developed mechanisms like Fe3+-siderophore and Fe2+-heme transport systems that help them absorb iron from their host.”
On a related note, because the levels of iron are so tightly regulated inside the human body, a significant change in the element’s physiological concentration can make the human body susceptible to bacterial infection. So, to counter bacterial invasions and the subsequent bacterial uptake of iron, the human body has developed smart defense mechanisms. For instance, during an active infection, the human body decreases the absorption of iron from the gut and directs iron to storage proteins, thus making it sparsely available to the invading bacteria.
Bacterial species have also developed strategic mechanisms for iron uptake. The most well-known mechanism involves the use of “siderophores”. Siderophores are bacteria-secreted chemical compounds that tightly bind to (and capture) ferric iron. They are secreted by invading bacteria in environments with iron deficits.
During recent years, researchers have introduced a clever innovation: they have chemically attached pharmaceutical drugs such as antibiotics to siderophores to ensure the successful delivery of therapeutics into the bacterial cytoplasm. For example, cefiderocol, an intravenously administered catechol-type siderophore cephalosporin, inhibits the synthesis of the outer membrane of gram-negative bacteria, thus eliminating these pathogens from the host system.
Scientists have also used siderophore-based systems as sensors for detecting bacteria. For example, Raman spectroscopy combined with the siderophore pyoverdine was used to detect the presence of Pseudomonas fluorescens, an infectious bacterium, even at ultra-low concentrations.
Dr. Shen concludes, “Future studies of human and bacterial iron metabolism and their interactions are expected to be very promising for the development of new treatments to tackle infection.”
Title of original paper: A zero-sum game or an interactive frame? Iron competition between bacteria and humans in infection war
Journal: Chinese Medical Journal
SOURCE Chinese Medical Journal