Biology subjects

Morowitz, M.

Publications and source records attributed to Morowitz, M..

7 recordsLinked to original sources

bioRxiv2025

Megaplasmids associate with Escherichia coli and other Enterobacteriaceae

Humans and animals are ubiquitously colonized by Enterobacteriaceae, a bacterial family that contains both commensals and clinically significant pathogens. Here, we report Enterobacteriaceae megaplasmids of up to 1.58 Mbp in length in infant and adult guts, and other microbiomes. Of 19 complete plasmid genomes, one was reconstructed from an E. coli isolate; others were linked to species of Citrobacter and Enterobacter via analysis of genome modification patterns. The detection of related plasmids in different Enterobacteriaceae, conjugation machinery, and more diverse modified motifs in certain plasmids compared to hosts suggests that these elements are self-transmissible, with a broad host range. The plasmids encode multi-drug efflux systems and potential secreted effectors. Up to 208 tRNAs are encoded and include sequence variants that may counter tRNA-centric defense mechanisms. Overall, the vast megaplasmid coding capacity may broaden host range, increase competitiveness, control invasion by other elements, and counter programmed cell death.

microbiology↗

bioRxiv2023

Infant gut bacteriophage strain persistence during the first three years of life

Bacteriophages are key components of gut microbiomes, yet the phage colonization process in the infant gut remains uncertain. Here, we established a large phage sequence database and used strain-resolved analyses to investigate phage succession in infants throughout the first three years of life. Analysis of 819 fecal metagenomes collected from 28 full-term and 24 preterm infants and their mothers revealed that early-life phageome richness increased over time and reached adult-like complexity by age three. Approximately 9% of early phage colonizers, mostly maternally transmitted and infecting Bacteroides, persisted for three years and were more prevalent in full-term than in preterm infants. Although rare, phages with stop codon reassignment were more likely to persist than non-recoded phages and generally displayed an increase in in-frame re-assigned stop codons over three years. Overall, maternal seeding, stop codon reassignment, host CRISPR-Cas locus prevalence, and diverse phage populations contribute to stable viral colonization.

microbiology↗

bioRxiv2022

Validation that human microbiome phages use alternative genetic coding with TAG stop read as Q

Metagenomic findings suggesting that bacteriophages (phages) can use genetic codes different from those of their host bacteria reveal a new dimension of phage-host interaction dynamics. Whereas reassignment of stop codons to code for amino acids has been predicted, there has been no proteomic validation of alternative coding in phages. In fact, one code where the stop codon TAG is reassigned to glutamine (code 15) has never been experimentally validated in any biological system. Here, we characterized stop codon reassignment in two crAss-like phages found in the human gut microbiome using LC-MS/MS-based metaproteomics. The proteome data from several phage structural proteins clearly demonstrates reassignment of the TAG stop codon to glutamine, establishing for the first time the expression of genetic code 15. One-Sentence SummaryMass spectrometry confirms protein expression of predicted alternate genetic coding in phage genomes from human microbiomes.

systems biology↗

bioRxiv2021

Infant gut strain persistence is associated with maternal origin, phylogeny, and functional potential including surface adhesion and iron acquisition

Gut microbiome succession impacts infant development. However, it remains unclear what factors promote persistence of initial bacterial colonists in the developing gut. Here, we performed strain-resolved metagenomic analyses to compare gut colonization of preterm and full-term infants throughout the first year of life and evaluated links between strain persistence and strain origin as well as genetic potential. Analysis of 206 fecal metagenomes collected from full-term and preterm infants and their mothers revealed that infants initially distinct microbial communities converged by age one. Approximately 11% of early colonists, primarily Bacteroides and Bifidobacterium, persisted during the first year of life, and these were more prevalent in full-term compared to preterm infants. Gut-associated strains from mothers were significantly more likely to persist in the infant gut than other strains. Enrichment in genes for surface adhesion, iron acquisition and carbohydrate degradation may explain persistence of some strains through the first year of life.

microbiology↗

bioRxiv2020

InStrain enables population genomic analysis from metagenomic data and rigorous detection of identical microbial strains

Coexisting microbial cells of the same species often exhibit genetic differences that can affect phenotypes ranging from nutrient preference to pathogenicity. Here we present inStrain, a program that utilizes metagenomic paired reads to profile intra-population genetic diversity (microdiversity) across whole genomes and compare populations in a microdiversity-aware manner, dramatically increasing genomic comparison accuracy when benchmarked against existing methods. We use inStrain to profile >1,000 fecal metagenomes from newborn premature infants and find that siblings share significantly more strains than unrelated infants, although identical twins share no more strains than fraternal siblings. Infants born via cesarean section harbored Klebsiella with significantly higher nucleotide diversity than infants delivered vaginally, potentially reflecting acquisition from hospital versus maternal microbiomes. Genomic loci showing diversity within an infant included variants found in other infants, possibly reflecting inoculation from diverse hospital-associated sources. InStrain can be applied to any metagenomic dataset for microdiversity analysis and rigorous strain comparison.

microbiology↗

bioRxiv2019

Clades of huge phage from across Earth’s ecosystems

Phage typically have small genomes and depend on their bacterial hosts for replication. DNA sequenced from many diverse ecosystems revealed hundreds of huge phage genomes, between 200 kbp and 716 kbp in length. Thirty-four genomes were manually curated to completion, including the largest phage genomes yet reported. Expanded genetic repertoires include diverse and new CRISPR-Cas systems, tRNAs, tRNA synthetases, tRNA modification enzymes, translation initiation and elongation factors, and ribosomal proteins. Phage CRISPR-Cas systems have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phage may repurpose bacterial CRISPR-Cas systems to eliminate competing phage. We phylogenetically define major clades of huge phage from human and other animal microbiomes, oceans, lakes, sediments, soils and the built environment. We conclude that their large gene inventories reflect a conserved biological strategy, observed over a broad bacterial host range and across Earths ecosystems.

microbiology↗

bioRxiv2018

Shifts in microbial transcription patterns prior to onset of Necrotizing enterocolitis may indicate low oxygen levels in the gut

Premature infants are at risk for developing necrotizing enterocolitis (NEC), an inflammatory disease that can progress to necrosis of gut tissue. Previous attempts have failed to identify any consistent predictor of NEC. We hypothesized that prior to the appearance of NEC symptoms, the gut microbiome shifts in its transcriptional profile. To test this hypothesis we integrated genome-resolved metagenomic and metatranscriptomic data from multiple time-points in the first month of life of four preterm infants, two of whom later developed NEC. Gut microbiomes of NEC infants showed increased transcription of high oxygen affinity cytochrome oxidases and lower transcription of genes to detoxify nitric oxide, an antimicrobial compound released by host cells. These results, and high transcription of H2 production genes, suggest low O2 conditions prior to NEC onset, and are consistent with hypoxic conditions in diseased gut tissue. The findings motivate further testing of transcript data as a predictor of NEC.\n\nHighlightsO_LITranscription of high oxygen affinity microbial cytochrome oxidase may predict necrotizing enterocolitis (NEC) development.\nC_LIO_LILower transcription of microbial genes to detoxify nitric oxide (NO) may also predict NEC development.\nC_LIO_LIHigher transcription of H2 production genes by Escherichia sp. was found in the gut of premature infants that develop NEC.\nC_LI

microbiology↗