Somānanda

Nemec, John

doi:10.1002/9781119009924.eopr0370

Cited by 1 publication

(1 citation statement)

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“…The ACB clade has substantially increased its repertoire of catabolic pathways for alternative carbon sources compared to taxa outside this clade [94]. For a small number of mostly handpicked A. baumannii strains, previous studies have experimentally confirmed the ability to grow on tricarballylate and putrescine, malonate, butanediol and acetoin, phenylacetate, muconate, glucarate, galactarate (mucate), and 4-hydroxyproline as sole carbon sources [40,85].…”

Section: Carbohydrate Catabolismmentioning

confidence: 99%

Evolutionarily stable gene clusters shed light on the common grounds of pathogenicity in the Acinetobacter calcoaceticus-baumannii complex

Djahanschiri

Venanzio

Distel

et al. 2022

Preprint

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Nosocomial pathogens of the Acinetobacter calcoaceticus-baumannii (ACB) complex are a cautionary example for the world-wide spread of multi- and pan-drug resistant bacteria. Aiding the urgent demand for novel therapeutic targets, comparative genomics studies between pathogens and their apathogenic relatives shed light on the genetic basis of human-pathogen interaction. Yet, existing studies are limited in taxonomic scope, sensing of the phylogenetic signal, and resolution by largely analyzing genes isolated from their functional contexts. Here, we explored more than 3,000 Acinetobacter genomes in a phylogenomic framework integrating orthology-based phylogenetic profiling and micro-synteny conservation analyses. This allowed to delineate gene clusters in the type strain A. baumannii ATCC 19606 whose evolutionary conservation indicates a functional integration of the subsumed genes. These evolutionarily stable gene clusters (ESGCs) reveal metabolic pathways, transcriptional regulators residing next to their targets but also tie together sub-clusters with distinct functions to form higher-order functional modules. We shortlisted 150 ESGCs that either co-emerged with, or are found preferentially in, the pathogenic ACB clade. They unveil, at an unprecedented resolution, the genetic makeup that coincides with the manifestation of the pathogenic phenotype in the last common ancestor of the ACB clade. Key innovations are the remodeling of the regulatory-effector cascade connecting LuxR/LuxI quorum sensing via an intermediate messenger to biofilm formation, the extension of micronutrient scavenging systems, and the increase of metabolic flexibility by exploiting carbon sources that are provided by the human host. Specifically, we could show that only members of the ACB clade use kynurenine as a sole carbon and energy source, a substance produced by humans to fine-tune the antimicrobial innate immune response. In summary, this study provides a rich and unbiased set of novel testable hypotheses on how pathogenic Acinetobacter interact with and ultimately infect their human host. They disclose promising routes for future therapeutic strategies.

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Section: Carbohydrate Catabolismmentioning

confidence: 99%