Pathogen elimination by probiotic Bacillus via signalling interference.

Probiotic nutrition is frequently claimed to improve human health. In particular, live probiotic bacteria obtained with food are thought to reduce intestinal colonization by pathogens, and thus to reduce susceptibility to infection. However, the mechanisms that underlie these effects remain poorly understood. Here we report that the consumption of probiotic Bacillus bacteria comprehensively abolished colonization by the dangerous pathogen Staphylococcus aureus in a rural Thai population. We show that a widespread class of Bacillus lipopeptides, the fengycins, eliminates S. aureus by inhibiting S. aureus quorum sensing-a process through which bacteria respond to their population density by altering gene regulation. Our study presents a detailed molecular mechanism that underlines the importance of probiotic nutrition in reducing infectious disease. We also provide evidence that supports the biological significance of probiotic bacterial interference in humans, and show that such interference can be achieved by blocking a pathogen's signalling system. Furthermore, our findings suggest a probiotic-based method for S. aureus decolonization and new ways to fight S. aureus infections.

Nonadiabatic Derivative Couplings through Multiple Franck-Condon Modes Dictate the Energy Gap Law for Near and Short-Wave Infrared Dye Molecules.

Near infrared (NIR, 700-1000 nm) and short-wave infrared (SWIR, 1000-2000 nm) dye molecules exhibit significant nonradiative decay rates from the first singlet excited state to the ground state. While these trends can be empirically explained by a simple energy gap law, detailed mechanisms of nearly universal behavior have remained unsettled for many cases. Theoretical and experimental results for two representative NIR/SWIR dye molecules reported here clarify the key mechanism for the observed energy gap law behavior. It is shown that the first derivative nonadiabatic coupling terms serve as major coupling pathways for nonadiabatic decay processes from the first excited singlet state to the ground state for these NIR and SWIR dye molecules and that vibrational modes other than the highest frequency modes also make significant contributions to the rate. This assessment is corroborated by further theoretical comparison with possible alternative mechanisms of intersystem crossing to triplet states and also by comparison with experimental data for deuterated molecules.

Elucidating ultranarrow 2F7/2 to 2F5/2 absorption in ytterbium(iii) complexes.

Achieving ultranarrow absorption linewidths in the condensed phase enables optical state preparation of specific non-thermal states, a prerequisite for quantum-enabled technologies. The 4f orbitals of lanthanide(iii) complexes are often referred to as "atom-like," reflecting their isolated nature, and are promising substrates for the optical preparation of specific quantum states. To better understand the photophysical properties of 4f states and assess their potential for quantum applications, theoretical building blocks are required for rapid screening. In this study, an atomic-level perturbative calculation (i.e., spin-orbit crystal field, SOCF) is applied to various Yb(iii) complexes to investigate their linear absorption and emission through a fitting mechanism of their experimentally determined transition energies and oscillator strengths. In particular, the optical properties of (thiolfan)YbCl(THF) (thiolfan = 1,1'-bis(2,4-di-tert-butyl-6-thiomethylenephenoxy)ferrocene), a recently reported complex with an ultranarrow optical linewidth, are computed and compared to those of other Yb(iii) compounds. Through a transition energy sampling study, major contributors to the optical linewidth are identified. We observe particularly isolated f-f transitions and narrow linewidths, which we attribute to two distinct factors. Firstly, the ultra-high atomic similarity of the orbitals involved in the optical transition, along with the presence of an anisotropic crystal field, collectively contribute to the observed narrow transitions. Secondly, we note highly correlated excited-ground energy fluctuations that serve to greatly suppress inhomogeneous line-broadening. This article illustrates how SOCF can be used as a low-cost method to probe the influence of crystal field environment on the optical properties of Yb(iii) complexes to assist the development of novel lanthanide series quantum materials.

Toward liquid cell quantum sensing: Ytterbium complexes with ultranarrow absorption.

The energetic disorder induced by fluctuating liquid environments acts in opposition to the precise control required for coherence-based sensing. Overcoming fluctuations requires a protected quantum subspace that only weakly interacts with the local environment. We report a ytterbium complex that exhibited an ultranarrow absorption linewidth in solution at room temperature with a full width at half maximum of 0.625 milli-electron volts. Using spectral hole burning, we measured an even narrower linewidth of 410 pico-electron volts at 77 kelvin. Narrow linewidths allowed low-field magnetic circular dichroism at room temperature, used to sense Earth-scale magnetic fields. These results demonstrated that ligand protection in lanthanide complexes could substantially diminish electronic state fluctuations. We have termed this system an "atomlike molecular sensor" (ALMS) and proposed approaches to improve its performance.

Growth and Stress Tolerance Comprise Independent Metabolic Strategies Critical for Staphylococcus aureus Infection.

Staphylococcus aureus is an important pathogen that leads to high morbidity and mortality. Although S. aureus produces many factors important for pathogenesis, few have been validated as playing a role in the pathogenesis of S. aureus pneumonia. To gain a better understanding of the genetic elements required for S. aureus pathogenesis in the airway, we performed an unbiased genome-wide transposon sequencing (Tn-seq) screen in a model of acute murine pneumonia. We identified 136 genes important for bacterial survival during infection, with a high proportion involved in metabolic processes. Phenotyping 80 individual deletion mutants through diverse in vitro and in vivo assays demonstrated that metabolism is linked to several processes, which include biofilm formation, growth, and resistance to host stressors. We further validated the importance of 23 mutations in pneumonia. Multivariate and principal-component analyses identified two key metabolic mechanisms enabling infection in the airway, growth (e.g., the ability to replicate and form biofilms) and resistance to host stresses. As deep validation of these hypotheses, we investigated the role of pyruvate carboxylase, which was important across multiple infection models and confirmed a connection between growth and resistance to host cell killing. Pathogenesis is conventionally understood in terms of the host-pathogen interactions that enable a pathogen to neutralize a host's immune response. We demonstrate with the important bacterial pathogen S. aureus that microbial metabolism influences key traits important for in vivo infection, independent from host immunomodulation. IMPORTANCE Staphylococcus aureus is an important bacterial pathogen that causes significant morbidity and mortality, infecting numerous bodily sites, including the respiratory tract. To identify the bacterial requirements for lung infection, we conducted a genome-wide screen in a mouse model of acute pneumonia. We discovered that metabolic genes were overrepresented in those required for lung infection. In contrast to the conventional view of pathogenesis focusing on immunomodulation, we demonstrate through phenotyping of deletion mutants in several functional assays that replicative ability and tolerance against host defenses form two key metabolic dimensions of bacterial infection. These dimensions are independent for most pathways but are coupled in central carbon metabolism and highlight the critical role of bacterial metabolism in survival against host defenses during infection.