Mobile-CRISPRi as a powerful tool for modulating<i>Vibrio</i>gene expression

Geyman, Logan; Tanner, Madeline; Rosario-Melendez, Natalia; Peters, Jason; Mandel, Mark J.; van Kessel, Julia C.

doi:10.1101/2024.01.17.575898

Cited by 2 publications

(1 citation statement)

References 29 publications

(56 reference statements)

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“…Genes that are critical in one strain, such as RscS, may be absent or altered in other strains, leading to a re-routing of regulatory pathways that may be informative to a more global view of host colonization ( 108 , 172 ). Adaptation of additional tools and techniques, including CRISPRi [now in progress ( 181 )] and RNAi, could facilitate the analysis of strains of interest that are less genetically tractable to explore the diversity of mechanisms that can drive the underlying phenotype.…”

Section: Future Directionsmentioning

confidence: 99%

Lighting the way: how the Vibrio fischeri model microbe reveals the complexity of Earth’s “simplest” life forms

Septer,

Visick

2024

J Bacteriol

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Vibrio ( Aliivibrio ) fischeri ’s initial rise to fame derived from its alluring production of blue-green light. Subsequent studies to probe the mechanisms underlying this bioluminescence helped the field discover the phenomenon now known as quorum sensing. Orthologs of quorum-sensing regulators (i.e., LuxR and LuxI) originally identified in V. fischeri were subsequently uncovered in a plethora of bacterial species, and analogous pathways were found in yet others. Over the past three decades, the study of this microbe has greatly expanded to probe the unique role of V. fischeri as the exclusive symbiont of the light organ of the Hawaiian bobtail squid, Euprymna scolopes . Buoyed by this optically amenable host and by persistent and insightful researchers who have applied novel and cross-disciplinary approaches, V. fischeri has developed into a robust model for microbe-host associations. It has contributed to our understanding of how bacteria experience and respond to specific, often fluxing environmental conditions and the mechanisms by which bacteria impact the development of their host. It has also deepened our understanding of numerous microbial processes such as motility and chemotaxis, biofilm formation and dispersal, and bacterial competition, and of the relevance of specific bacterial genes in the context of colonizing an animal host. Parallels in these processes between this symbiont and bacteria studied as pathogens are readily apparent, demonstrating functional conservation across diverse associations and permitting a reinterpretation of “pathogenesis.” Collectively, these advances built a foundation for microbiome studies and have positioned V. fischeri to continue to expand the frontiers of our understanding of the microbial world inside animals.

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Section: Future Directionsmentioning

confidence: 99%

Lighting the way: how the Vibrio fischeri model microbe reveals the complexity of Earth’s “simplest” life forms

Septer,

Visick

2024

J Bacteriol

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Chemical genomics informs antibiotic and essential gene function inAcinetobacter baumannii

Tran,

Ward,

Iruegas-López

et al. 2024

Preprint

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The Gram-negative pathogen, Acinetobacter baumannii, poses a serious threat to human health due to its role in nosocomial infections that are resistant to treatment with current antibiotics. Despite this, our understanding of fundamental A. baumannii biology remains limited, as many essential genes have not been experimentally characterized. These essential genes are critical for bacterial survival and, thus, represent promising targets for drug discovery. Here, we systematically probe the function of essential genes by screening a CRISPR interference knockdown library against a diverse panel of chemical inhibitors, including antibiotics. We find that most essential genes show chemical-gene interactions, allowing insights into both inhibitor and gene function. For instance, knockdown of lipooligosaccharide (LOS) transport genes increased sensitivity to a broad range of chemicals. Cells with defective LOS transport showed cell envelope hyper-permeability that was dependent on continued LOS synthesis. Using phenotypes across our chemical-gene interaction dataset, we constructed an essential gene network linking poorly understood genes to well-characterized genes in cell division and other processes. Finally, our phenotype-structure analysis identified structurally related antibiotics with distinct cellular impacts and suggested potential targets for underexplored inhibitors. This study advances our understanding of essential gene and inhibitor function, providing a valuable resource for mechanistic studies, therapeutic strategies, and future key targets for antibiotic development.

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Mobile-CRISPRi as a powerful tool for modulatingVibriogene expression

Cited by 2 publications

References 29 publications

Lighting the way: how the Vibrio fischeri model microbe reveals the complexity of Earth’s “simplest” life forms

Lighting the way: how the Vibrio fischeri model microbe reveals the complexity of Earth’s “simplest” life forms

Chemical genomics informs antibiotic and essential gene function inAcinetobacter baumannii

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