Current opinion in microbiology最新文献

Designing microbiomes for applications in health, bioengineering, and sustainability is intrinsically linked to a fundamental theoretical understanding of the rules governing microbial community assembly. Microbial ecologists have used a range of mathematical models to understand, predict, and control microbiomes, ranging from mechanistic models, putting microbial populations and their interactions as the focus, to purely statistical approaches, searching for patterns in empirical and experimental data. We review the success and limitations of these modeling approaches when designing novel microbiomes, especially when guided by (inevitably) incomplete experimental data. Although successful at predicting generic patterns of community assembly, mechanistic and phenomenological models tend to fall short of the precision needed to design and implement specific functionality in a microbiome. We argue that to effectively design microbiomes with optimal functions in diverse environments, ecologists should combine data-driven techniques with mechanistic models - a middle, third way for using theory to inform design.

The molecular essence of the battle between host and pathogens lies in the protein-protein or protein-metabolite interactions. Itaconate is one of the most upregulated immunometabolites, regulating immune responses through either noncovalent binding or covalent modification in the host. We herein briefly review recent progresses in the discoveries of physiological and pathological roles of itaconate and applications of chemical proteomic technologies in exploring itaconate modifications on cysteines (S-itaconation) at the interface of host-pathogen interactions. Key challenges are also proposed as future outlook.

The gut microbiome impacts human health in direct and indirect ways. While many associations have been discovered between specific microbiome compositions and diseases, establishing causality, understanding the underlying mechanisms, and developing successful microbiome-based therapies require novel experimental approaches. In this opinion, we discuss how in vitro cultivation of diverse communities enables systematic investigation of the individual and collective functions of gut microbes. Up to now, the field has relied mostly on simple, bottom-up assembled synthetic communities or more complex, undefined stool-derived communities. Although powerful for dissecting interactions and mapping causal effects, these communities suffer either from ignoring the complexity, diversity, coevolution, and dynamics of natural communities or from lack of control of community composition. These limitations can be overcome in the future by establishing personalized culture collections from stool samples of different donors and assembling personalized communities to investigate native interactions and ecological relationships in a controlled manner.

Genome editing technologies, such as CRISPR-Cas9, have revolutionised the study of genes in a variety of organisms, including unicellular parasites. Today, the CRISPR-Cas9 technology is vastly applied in high-throughput screens to investigate interactions between the Apicomplexan parasite Toxoplasma gondii and its hosts. In vitro and in vivo T. gondii screens performed in naive and restrictive conditions have led to the discovery of essential and fitness-conferring T. gondii genes, as well as factors important for virulence and dissemination. Recent studies have adapted the CRISPR-Cas9 screening technology to study T. gondii genes based on phenotypes unrelated to parasite survival. These advances were achieved by using conditional systems coupled with imaging, as well as single-cell RNA sequencing and phenotypic selection. Here, we review the state-of-the-art of CRISPR-Cas9 screening technologies with a focus on T. gondii, highlighting strengths, current limitations and future avenues for its development, including its application to other Apicomplexan species.

Natural products have been pivotal in treating mycobacterial infections with early antibiotics such as streptomycin, forming the foundation of tuberculosis therapy. However, the emergence of multidrug-resistant and extensively drug-resistant Mycobacterium species has intensified the need for novel antimycobacterial agents. In this review, we revisit the historical contributions of natural products to antimycobacterial drug discovery and highlight recent advances in the field. We assess the application of molecular networking and the exploration of unculturable bacteria in identifying new antimycobacterial compounds such as amycobactin and levesquamides. We also highlight the role of semisynthesis in optimizing natural products, exemplified by sequanamycins and spectinomycin analogs that evade M. tuberculosis' intrinsic resistance. Finally, we discuss emerging technologies that are promising to accelerate the discovery and development of next-generation antimycobacterial therapies. Despite ongoing challenges, these innovative approaches offer renewed hope in addressing the growing crisis of drug-resistant mycobacterial infections.

As a class of natural compounds ubiquitous in nature, diverse terpenoids exhibit a broad spectrum of applications in human endeavors. The efficient discovery of novel terpenoids and the establishment of a terpene library for broad utilization represent pressing challenges in terpenoid natural product research. Various microbial platforms offer abundant precursors for terpene biosynthesis from diverse sources. Leveraging artificial intelligence for enzyme function prediction and screening can facilitate the identification of terpenoid synthesis components with innovative mechanisms. Automated high-throughput bio-foundry workstations can expedite the construction of terpenoid libraries, providing substantial time and labor savings. The integration of multiple strategies promises to yield substantial advancements in the exploration of valuable terpenoids.

Microbial ammonia oxidation plays an important role in nitrogen (N₂) cycling in natural and man-made systems. Heterotrophic microorganisms that oxidize ammonia were observed more than a century ago; however, the underlying molecular mechanism of ammonia oxidation is still mysterious. Dirammox (direct ammonia oxidation to N₂) is a newly described heterotrophic ammonia oxidation process in which ammonia or its organic amine is oxidized into hydroxylamine and then directly converted to N₂ gas without the involvement of nitrite and nitrate. As demonstrated with Alcaligenes species, the conversion of ammonia to hydroxylamine is mediated by the dnf genes, and hydroxylamine conversion to N₂ is considered both a biotic and abiotic process. Dirammox is different from the N₂-producing processes of nitrification-denitrification and anaerobic ammonia oxidation (anammox), in which nitrite or nitrate is involved. Here, we review the discovery of dirammox, progress toward understanding its genetics, biochemistry, physiology, and ecology, and future perspectives and directions.

Brown algae, constituting the second largest group of marine macroalgae, fix significant amounts of inorganic carbon into alginate, the most abundant polysaccharide found in their cell walls. Alginate serves as an important macromolecular carbon source for marine bacteria. The catabolism of alginate by bacteria is an important step in the marine carbon cycle, and this area of research has attracted growing interests over the past decade. Here, we provide an overview of the recent advances in our understanding of marine bacterial alginate catabolic systems, both in individual organisms and within bacterial consortia, discuss the possibility of additional alginate metabolic pathways in light of the present findings, and highlight the future research foci.

CRISPR-associated transposons (CASTs) are naturally occurring amalgamations of CRISPR-Cas machinery and Tn7-like transposons that direct site-specific integration of transposon DNA via programmable guide RNAs. Although the mechanisms of CAST-based transposition have been well studied at the molecular and structural level, CASTs have yet to be broadly applied to bacterial genome engineering and systematic gene phenotyping (i.e. functional genomics) - likely due to their relatively recent discovery. Here, we describe the function and applications of CASTs, focusing on well-characterized systems, including the type I-F CAST from Vibrio cholerae (VcCAST) and type V-K CAST from Scytonema hofmanni (ShCAST). Further, we discuss the potentially transformative impact of targeted transposition on bacterial functional genomics by proposing genome-scale extensions of existing CAST tools.