Coherent Electron Transport across a 3 nm Bioelectronic Junction Made of Multi-Heme Proteins

Multi-heme cytochromes (MHCs) are fascinating proteins used by bacterial organisms to shuttle electrons within, between, and out of their cells. When placed in solid-state electronic junctions, MHCs support temperature-independent currents over several nanometers that are 3 orders of magnitude higher compared to other redox proteins of similar size. To gain molecular-level insight into their astonishingly high conductivities, we combine experimental photoemission spectroscopy with DFT+Σ current-voltage calculations on a representative Gold-MHC-Gold junction. We find that conduction across the dry, 3 nm long protein occurs via off-resonant coherent tunneling, mediated by a large number of protein valence-band orbitals that are strongly delocalized over heme and protein residues. This picture is profoundly different from the electron hopping mechanism induced electrochemically or photochemically under aqueous conditions. Our results imply that the current output in solid-state junctions can be even further increased in resonance, for example, by applying a gate voltage, thus allowing a quantum jump for next-generation bionanoelectronic devices

Nanosecond heme-to-heme electron transfer rates in a multiheme cytochrome nanowire reported by a spectrally unique His/Met-ligated heme.

Proteins achieve efficient energy storage and conversion through electron transfer along a series of redox cofactors. Multiheme cytochromes are notable examples. These proteins transfer electrons over distance scales of several nanometers to >10 μm and in so doing they couple cellular metabolism with extracellular redox partners including electrodes. Here, we report pump-probe spectroscopy that provides a direct measure of the intrinsic rates of heme-heme electron transfer in this fascinating class of proteins. Our study took advantage of a spectrally unique His/Met-ligated heme introduced at a defined site within the decaheme extracellular MtrC protein of Shewanella oneidensis We observed rates of heme-to-heme electron transfer on the order of 109 s-1 (3.7 to 4.3 Å edge-to-edge distance), in good agreement with predictions based on density functional and molecular dynamics calculations. These rates are among the highest reported for ground-state electron transfer in biology. Yet, some fall 2 to 3 orders of magnitude below the Moser-Dutton ruler because electron transfer at these short distances is through space and therefore associated with a higher tunneling barrier than the through-protein tunneling scenario that is usual at longer distances. Moreover, we show that the His/Met-ligated heme creates an electron sink that stabilizes the charge separated state on the 100-μs time scale. This feature could be exploited in future designs of multiheme cytochromes as components of versatile photosynthetic biohybrid assemblies

The cytochrome bd-I respiratory oxidase augments survival of multidrug-resistant Escherichia coli during infection

Nitric oxide (NO) is a toxic free radical produced by neutrophils and macrophages in response to infection. Uropathogenic Escherichia coli (UPEC) induces a variety of defence mechanisms in response to NO, including direct NO detoxification (Hmp, NorVW, NrfA), iron-sulphur cluster repair (YtfE), and the expression of the NO-tolerant cytochrome bd-I respiratory oxidase (CydAB). The current study quantifies the relative contribution of these systems to UPEC growth and survival during infection. Loss of the flavohemoglobin Hmp and cytochrome bd-I elicit the greatest sensitivity to NO-mediated growth inhibition, whereas all but the periplasmic nitrite reductase NrfA provide protection against neutrophil killing and promote survival within activated macrophages. Intriguingly, the cytochrome bd-I respiratory oxidase was the only system that augmented UPEC survival in a mouse model after 2 days, suggesting that maintaining aerobic respiration under conditions of nitrosative stress is a key factor for host colonisation. These findings suggest that while UPEC have acquired a host of specialized mechanisms to evade nitrosative stresses, the cytochrome bd-I respiratory oxidase is the main contributor to NO tolerance and host colonisation under microaerobic conditions. This respiratory complex is therefore of major importance for the accumulation of high bacterial loads during infection of the urinary tract

Rational Design of Covalent Multiheme Cytochrome-Carbon Dot Biohybrids for Photoinduced Electron Transfer

AbstractBiohybrid systems can combine inorganic light‐harvesting materials and whole‐cell biocatalysts to utilize solar energy for the production of chemicals and fuels. Whole‐cell biocatalysts have an intrinsic self‐repair ability and are able to produce a wide variety of multicarbon chemicals in a sustainable way with metabolic engineering. Current whole‐cell biohybrid systems have a yet undefined electron transfer pathway between the light‐absorber and metabolic enzymes, limiting rational design. To enable engineering of efficient electron transfer pathways, covalent biohybrids consisting of graphitic nitrogen doped carbon dots (g‐N‐CDs) and the outer‐membrane decaheme protein, MtrC from Shewanella oneidensis MR‐1 are developed. MtrC is a subunit of the MtrCAB protein complex, which provides a direct conduit for bidirectional electron exchange across the bacterial outer membrane. The g‐N‐CDs are functionalized with a maleimide moiety by either carbodiimide chemistry or acyl chloride activation and coupled to a surface‐exposed cysteine of a Y657C MtrC mutant. MtrC∼g‐N‐CD biohybrids are characterized by native and denaturing gel electrophoresis, chromatography, microscopy, and fluorescence lifetime spectroscopy. In the presence of a sacrificial electron donor, visible light irradiation of the MtrC∼g‐N‐CD biohybrids results in reduced MtrC. The biohybrids may find application in photoinduced transmembrane electron transfer in S. oneidensis MR‐1 for chemical synthesis in the future.</jats:p

Characterizing wheeze phenotypes to identify endotypes of childhood asthma, and the implications for future management

It is now a commonly held view that asthma is not a single disease, but rather a set of heterogeneous diseases sharing common symptoms. One of the major challenges in treating asthma is understanding these different asthma phenotypes and their underlying biological mechanisms. This review gives an epidemiological perspective of our current understanding of the different phenotypes that develop from birth to childhood that come under the umbrella term 'asthma'. The review focuses mainly on publications from longitudinal birth cohort studies where the natural history of asthma symptoms is observed over time in the whole population. Identifying distinct pathophysiological mechanisms for these different phenotypes will potentially elucidate different asthma endotypes, ultimately leading to more effective treatment and management strategies. © 2013 Informa UK Ltd