Mind the Gap—A Perspective on Strategies for Protecting against Bacterial Infections during the Period from Infection to Eradication

Abstract

The emergence of antibiotic-resistant bacteria is a pressing public health concern, highlighting the need for alternative approaches to control bacterial infections. Promising approaches include the development of therapeutic vaccines and the utilization of innate immune activation techniques, which may prove useful in conjunction with antibiotics, as well as other antibacterial modalities. However, innate activation should be fast and self- or actively- contained to prevent detrimental consequences. TLR ligand adjuvants are effective at rapidly activating, within minutes to hours, the innate immune system by inducing cytokine production and other signaling molecules that bolster the host’s immune response. Neutrophils serve as the first line of defense against invading pathogens by capturing and destroying them through various mechanisms, such as phagocytosis, intracellular degradation, and the formation of NETs. Nutritional immunity is another host defense mechanism that limits the availability of essential metals, such as iron, from invading bacterial pathogens. Thus, iron starvation has been proposed as a potential antibacterial strategy. In this review, we focus on approaches that have the potential to enhance rapid and precise antibacterial responses, bridging the gap between the onset of infection and the elimination of bacteria, hence limiting the infection by antibiotic-resistant bacteria.

Iron Overload in Brain: Transport Mismatches, Microbleeding Events, and How Nanochelating Therapies May Counteract Their Effects

“…Finally, iron is strictly necessary for the proliferation of microorganisms (A4 in Table 1), such as bacteria, viruses, and fungi [38]. Nutritional immunity is another host defense mechanism that limits the availability of essential metals, such as iron, from invading bacterial pathogens, and iron starvation has been proposed as a potential antibacterial strategy [39]. The mechanism used by bacteria, e.g., Staphylococcus aureus, to extract iron from Hb has been recently identified [40] in two receptors, IsdB and IsdH, exposed to the surface of the bacterium, being the first of them formed by NEAT (Near Iron Transports) domains, which bind heme from the ferric form of Hb, accelerating its release up to 2000 fold.…”