Multidrug-resistant Escherichia coli metabolomes are reprogrammed by glutamine to be sensitive to ampicillin in vitro and in vivo.

The Na ⁺ -NQR complex functions as a unique redox-driven sodium pump, generating membrane potential directly. However, whether it mediates generation of membrane potential indirectly is unknown. The present study shows that the Na ⁺ -NQR complex impacts membrane potential through other antiporter families Atp and Mnh. It proceeds by ATP and then cAMP/CRP regulon, which inhibits l- alanine catabolism and promotes l- alanine anabolism. When the Na ⁺ -NQR complex is reduced as in antibiotic-resistant bacteria, l- alanine is depressed, which is related to the antibiotic resistance phenotypes. However, exogenous l- alanine reverts the phenotype and promotes antibiotic-mediated killing. These findings suggest a novel mechanism by which the Na ⁺ -NQR system regulates antibiotic resistance via l- alanine metabolism in a cAMP/CRP complex-dependent manner.

Chen H, et al. Allergy Asthma Immunol Res. 2021 Mar;13(2):177-205. https://doi.org/10.4168/aair.2021.13.2.177

Development of low-cost and eco-friendly approaches to fight bacterial pathogens is especially needed in aquaculture. We previously showed that exogenous malate reprograms zebrafish’s metabolome to potentiate zebrafish survival against Vibrio alginolyticus infection. However, the underlying mechanism is unknown. Here, we use GC-MS based metabolomics to identify the malate-triggered metabolic shift. An activated TCA cycle and elevated taurine are identified as the key metabolic pathways and the most crucial biomarker of the reprogrammed metabolome, respectively. Taurine elevation is attributed to the activated TCA cycle, which is further supported by the increased expression of genes in the metabolic pathway of taurine biosynthesis from the isocitrate of the TCA cycle to taurine. Exogenous taurine increases the survival of zebrafish against V. alginolyticus infection as malate did. Moreover, exogenous taurine and malate regulate the expression of innate immunity genes and promote the generation of reactive oxygen species and nitrogen oxide in a similar way. The two metabolites can alleviate the excessive immune response to bacterial challenge, which protects fish from bacterial infection. These results indicate that malate enhances the survival of zebrafish to V. alginolyticus infection via taurine. Thus, our study highlights a metabolic approach to enhance a host’s ability to fight bacterial infection.

Cellular senescence is a complicated process featured by irreversible cell cycle arrest and senescence-associated secreted phenotype (SASP), resulting in accumulation of senescent cells, and low-grade inflammation. Cellular senescence not only occurs during the natural aging of normal cells, but also can be accelerated by various pathological factors. Cumulative studies have shown the role of cellular senescence in the pathogenesis of chronic lung diseases including chronic obstructive pulmonary diseases (COPD) and idiopathic pulmonary fibrosis (IPF) by promoting airway inflammation and airway remodeling. Recently, great interest has been raised in the involvement of cellular senescence in asthma. Limited but valuable data has indicated accelerating cellular senescence in asthma. This review will compile current findings regarding the underlying relationship between cellular senescence and asthma, mainly through discussing the potential mechanisms of cellular senescence in asthma, the impact of senescent cells on the pathobiology of asthma, and the efficiency and feasibility of using anti-aging therapies in asthmatic patients.

The present study explored the cooperative effect of both alanine (Ala) and gentamicin (Gent) on metabolic mechanisms by which exogenous Ala potentiates Gent to kill antibiotic-resistant Vibrio alginolyticus. To test this, GC-MS-based metabolomics was used to characterize Ala-, Gent- and both-induced metabolic profiles, identifying nitric oxide (NO) production pathway as the most key clue to understand metabolic mechanisms. Gent, Ala and both led to low, lower and lowest activity of total nitric oxide synthase (tNOS) and level of NO, respectively. NOS promoter L-arginine and inhibitor N^G-Monomethyl-L-arginine inhibited and promoted the killing, respectively, with the elevation and decrease of NOS activity and NO level. The present study further showed that CysJ is the enzyme-producing NO in V. alginolyticus. These results indicate that the cooperative effect of Ala and Gent causes the lowest NO, which plays a key role in Ala-potentiated Gent-mediated killing.