bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.06.04.597488

Emergence of Slc11 clade MCbgut: a parsimonious hypothesis for the dawn of Lactobacillales in the gut of early vertebrates

Abstract

The Lactobacillales (LB) stand apart among bacterial orders, using manganese (Mn) instead of iron to support their growth and swiftly ferment complex foods while acidifying their environment. The present work investigates whether a shift in the use of Mn could mark the origin of LB. Transmembrane carriers of the ubiquitous Slc11 family play key roles in LB physiology by catalyzing proton-dependent Mn import. In prior studies, the Slc11 clade found in LB (MntH Cb, MCb) showed both remarkable structural plasticity and highly efficient Mn uptake, and another Slc11 clade, MCg1, demonstrated divergent evolution coinciding with emergence of bacterial genera (e.g., Bordetella, Achromobacter). Herein, Slc11 clade MCb is subdivided in sister groups: MCbie and MCbgut. MCbie derives directly from Slc11 clade MCa, pointing an intermediate stage in the evolution of MCbgut. MCbie predominates in marine Bacillaceae, is more conserved than MCbgut, lacks the structural plasticity that typify MCbgut carriers, and responds differently to identical mutagenesis. Exchanging MCbie/MCbgut amino acid residues at sites that distinguish these clades showed conformation-dependent effects with both MCbie and MCbgut templates and the 3D location of the targeted sites in the carrier structure together suggest the mechanism to open the inner gate, and release Mn into the cytoplasm, differs between MCbie and MCbgut. Building on the established phylogeny for Enterococcus revealed that a pair of genes encoding MCbgut was present in the common ancestor of LB, as MCbgu1 and MCbgu2 templates exhibit distinct structural dynamics properties. These data are discussed examining whether MCb + LB could emerge in the upper gut of early vertebrates (ca. 540 mya), through genome contraction and evolution toward Mn-centrism, as they specialized as gastric aids favoring stomach establishment in jawed vertebrates through bi-directional communication with host nervous, endocrine and immune systems.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Cellier, M. F.. 2024-06-05. Emergence of Slc11 clade MCbgut: a parsimonious hypothesis for the dawn of Lactobacillales in the gut of early vertebrates. https://doi.org/10.1101/2024.06.04.597488

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis

Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.

microbiology↗

The iron-binding siderophore enterobactin is required for the response of multi-drug resistant Klebsiella pneumoniae to zinc limitation

To persist during infection Klebsiella pneumoniae must overcome nutrient iron and zinc limitation imposed by the host immune system through a process called nutritional immunity. Secreted small molecule siderophores are a major virulence determinant of Klebsiella pneumoniae pathogenesis and are presumed to overcome nutritional immunity by binding iron for bacterial acquisition. In this work, we set out to identify how a multi-drug resistant K. pneumoniae grows in zinc limited environments. Using unbiased transcriptomics, proteomics, and an arrayed transposon screen, we identified that synthesis and uptake of the siderophore enterobactin is required to allow for growth in low zinc conditions. Iron-specific chelators did not replicate this phenotype and addition of supplemental iron through heme in growth media could not complement severe growth defects of enterobactin mutant K. pneumoniae experiencing zinc limitation. Finally, zinc starvation induced enterobactin production independent of the canonical zinc uptake regulator (Zur) transcription factor suggesting an unidentified regulatory mechanism by which Gram-negative pathogens may respond to zinc stress. Together, these studies expand the role of enterobactin beyond iron regulation and highlight a previously unreported link between iron and zinc homeostasis in Klebsiella pneumoniae.

microbiology↗

A microbiota-derived protease links phage susceptibility to host epithelial responses

Bacteriophages are major ecological drivers of gut microbial ecology, yet whether bacterial mechanisms that determine phage susceptibility have consequences for the mammalian host remains poorly understood. Here, we identify dipeptidyl peptidase 11 (Dpp11a), the predominant active serine protease of the prevalent gut commensal Phocaeicola vulgatus, as an unexpected bacterial defence factor. Dpp11a protects against environmental proteases and confers resistance to bacteriophage infection. Metatranscriptomic analyses further reveal increased expression of both dpp11a and P. vulgatus-associated phage transcripts in ulcerative colitis stool samples, indicating that both components of this interaction are transcriptionally active in disease-associated human microbiomes. Using the microfluidic gut-on-a-chip co-culture model HuMiX, we show that the absence of Dpp11 is accompanied by altered epithelial tight-junction remodelling during phage-bacterial infection. Together, our findings reveal that the consequences of bacterial phage defence can extend beyond phage-bacterium interactions to the mammalian epithelium.

microbiology↗