Iron is an essential trace element for both humans and bacteria. It plays a vital role in life, such as in redox reactions and electron transport. Strict regulatory mechanisms are necessary to maintain iron homeostasis because both excess and insufficient iron are harmful to life. Competition for iron is a war between humans and bacteria. To grow, reproduce, colonize, and successfully cause infection, pathogens have evolved various mechanisms for iron uptake from humans, principally Fe3+-siderophore and Fe2+-heme transport systems. Humans have many innate immune mechanisms that regulate the distribution of iron and inhibit bacterial iron uptake to help resist bacterial invasion and colonization. Meanwhile, researchers have invented detection test strips and coupled antibiotics with siderophores to create tools that take advantage of this battle for iron, to help eliminate pathogens. In this review, we summarize bacterial and human iron metabolism, competition for iron between humans and bacteria, siderophore sensors, antibiotics coupled with siderophores, and related phenomena. We also discuss how competition for iron can be used for diagnosis and treatment of infection in the future.
As an absolute quantification method at the singlemolecule level, digital PCR (dPCR) offers the highest accuracy. In this work, we developed a 3D scalable chamber-array chip that multiplied the number of partitions by stacking chamber-array layers and realized digital loop-mediated isothermal amplification to quantify DNA molecules. It greatly increases the number of partitions to improve the performance of dPCR without increasing the chip size, the operation workflow complicity, and operation time. For the three-chamber-array-layer chip which contains 200,000 reactors of a 0.125 nL volume, it has been proved that the reagent filling and partition were finished within 3 min, and the whole detection could be finished within 1 h. The method demonstrated that it could be scalable to a six-chamber-array layer, which contains 400,000 reactors without increasing the size of the chip and the complication of filling/partition workflow but only takes an additional hour for scanning. Due to its potential for high throughput, low cost, and simple operation, our device may significantly expand the clinical application range of dPCR.
Microbes shape their habitats through consuming resources, as well as actively producing and secreting diverse chemicals. These chemicals serve various niche-construction functions and can be considered "public good" for the community. Most microorganisms, for instance, release small molecules known as siderophores to scavenge irons from the extracellular environment. Despite being exploitable by cheaters, biosynthetic genes producing such molecules widely exist in nature, invoking active investigation on the possible mechanisms for producers to survive cheater invasion. In this work, we utilized the chemostat-typed model to demonstrate that the division of the iron by private and public siderophores can promote stable or dynamical coexistence between the cheater and "partial cooperators", an adaptive strategy with the production of both public and private siderophores. Further, our analysis revealed that when microbes not only consume but also produce resources, this type of "resource partition model" exhibit different stability criteria than that of the classical consumer resource model, allowing more complex systems dynamics.
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