The biosynthesis mechanism of bacterioruberin in halophilic archaea revealed by genome and transcriptome analysis.

Halophilic archaea are promising microbial cell factories for bacterioruberin (BR) production. BR is a natural product with multi-bioactivities, allowing potential application in many fields. In the previous work, a haloarchaeon Halorubrum sp. HRM-150 with a high proportion of BR (about 85%) was isolated, but the low yield impeded its large-scale production. This work figured out BR synthesis characteristics and mechanisms, and proposed strategies for yield improvement. First, glucose (10 g/L) and tryptone (15 g/L) were tested to be better sources for BR production. Besides, the combination of glucose and starch achieved the diauxic growth, and the biomass and BR productivity increased by 85% and 54% than using glucose. Additionally, this work first proposed the BR synthesis pattern, which differs from that of other carotenoids. As a structural component of cell membranes, the BR synthesis is highly coupled with growth, which was most active in the logarithm phase. Meanwhile, the osmotic down shock at the logarithm phase could increase the BR productivity without sacrificing the biomass. Moreover, the de-novo pathway for BR synthesis with a key gene of lyeJ, and its competitive pathways (notably tetraether lipids and retinal) were revealed through genome, transcriptome, and osmotic down shock. Therefore, the BR yield is expected to be improved through mutant construction, such as the overexpression of key gene lyeJ and the knockout of competitive genes, which need to be further explored. The findings will contribute to a better understanding of the metabolism mechanism in haloarchaea and the development of haloarchaea as microbial cell factories. IMPORTANCE: Recent studies have revealed that halophilic microorganism is a promising microbial factory for the next-generation industrialization. Among them, halophilic archaea are advantageous as microbial factories due to their low contamination risk and low freshwater consumption. The halophilic archaea usually accumulate long chain C50 carotenoids, which are barely found in other organisms. Bacterioruberin (BR), the major C50 carotenoid, has multi-bioactivities, allowing potential application in food, cosmetic, and biomedical industries. However, the low yield impedes its large-scale application. This work figured out the BR synthesis characteristics and mechanism, and proposed several strategies for BR yield improvement, encouraging halophilic archaea to function as microbial factories for BR production. Meanwhile, the archaea have special evolutionary status and unique characteristics in taxonomy, the revelation of BR biosynthesis mechanism is beneficial for a better understanding of archaea.

Phenotypic and genomic insights into the pathogenicity and antimicrobial resistance of an Enterobacter roggenkampii strain isolated from diseased silver arowana (Osteoglossum bicirrhosum).

Enterobacter roggenkampii is an opportunistic pathogen that causes infections in a wide range of hosts. A bacterial strain named EOBSR_19 was isolated from diseased silver arowana, Osteoglossum bicirrhosum. This bacterium was identified as E. roggenkampii based on the phenotypic characteristics and sequence analysis of the16S rDNA and gyrB genes. Average nucleotide identity and phylogenetic analysis based on the whole genome sequence further confirmed the bacterial taxonomy of EOBSR_19. Artificial experimental infection indicated that EOBSR_19 was pathogenic to fish. Antimicrobial susceptibility test showed it was multi-drug resistant. The EOBSR_19 was found to be resistant to 18 antibiotics belonging to quinolones, macrolides, sulfonamides, aminoglycosides, and ß-lactams classes. The whole genome sequencing analysis showed that EOBSR_19 carried 730 virulence genes that were annotated for different functional modules, such as adhesion and invasion, secretion system, siderophore transport system and bacterial toxin. Among them, the virulence genes related to adhesion and invasion were the most abundant. In addition, drug resistance genes involved in multiple mechanisms of antimicrobial resistance were identified in its genomics, including multidrug resistance efflux pumps, antibiotic inactivating enzymes, and antibiotic binding site mutations. Its genomic analysis via whole-genome sequencing provided insights into the pathogenicity and antimicrobial resistance.

Advances and applications of fluids biomarkers in diagnosis and therapeutic targets of Alzheimer's disease.

AIMS: Alzheimer's disease (AD) is a neurodegenerative disease with challenging early diagnosis and effective treatments due to its complex pathogenesis. AD patients are often diagnosed after the appearance of the typical symptoms, thereby delaying the best opportunity for effective measures. Biomarkers could be the key to resolving the challenge. This review aims to provide an overview of application and potential value of AD biomarkers in fluids, including cerebrospinal fluid, blood, and saliva, in diagnosis and treatment. METHODS: A comprehensive search of the relevant literature was conducted to summarize potential biomarkers for AD in fluids. The paper further explored the biomarkers' utility in disease diagnosis and drug target development. RESULTS: Research on biomarkers mainly focused on amyloid-ß (Aß) plaques, Tau protein abnormal phosphorylation, axon damage, synaptic dysfunction, inflammation, and related hypotheses associated with AD mechanisms. Aß42 , total Tau (t-Tau), and phosphorylated Tau (p-Tau), have been endorsed for their diagnostic and predictive capability. However, other biomarkers remain controversial. Drugs targeting Aß have shown some efficacy and those that target BACE1 and Tau are still undergoing development. CONCLUSION: Fluid biomarkers hold considerable potential in the diagnosis and drug development of AD. However, improvements in sensitivity and specificity, and approaches for managing sample impurities, need to be addressed for better diagnosis.