Jeffrey Scott McLean

• PhD
• Professor (Associate) at University of Washington

All cultivated Patescibacteria, also known as the candidate phyla radiation, are obligate episymbionts residing on other microbes. Despite being ubiquitous in many diverse environments, including mammalian microbiomes, molecular mechanisms of host identification and binding amongst ultrasmall bacterial episymbionts remain largely unknown. Type 4 pi...

Saccharibacteria are episymbionts that require host-bacteria to grow. They are positively associated with inflammatory diseases within the human microbiome, yet their mechanisms for interacting with the human host and contributing to diseases remain unknown. This study investigated interactions between a Saccharibacterium ( Nanosynbacter lyticus ),...

Oral bacteria have been found in the colon in pathologies such as inflammatory bowel disease. To ascertain niche coalescence, 2 elements are essential: (i) paired oral/fecal samples and (ii) strain-level resolution. We profiled the microbiota in 283 samples from 39 patients undergoing intensive chemotherapy at baseline (saliva: 49, plaque: 51, stoo...

Here, we announce the complete genome sequence of Veillonella parvula strain PK1910, obtained from a frozen stock. The genome is composed of one closed contig with a length of 2,213,486 bp, resulting in 98.0× coverage containing 1,979 protein-coding genes, with a GC content of 38.74%.

Nanosynbacter sp. strain BB002, was isolated from the human oral cavity on its basibiont bacterial host Actinomyces sp. oral taxon 171 strain F0337, related to Actinomyces oris. As a member of the Saccharibacteria within the candidate phylum radiation group (CPR), its reduced genome facilitates the survival as an ultrasmall (<0.2 μm) epibiont.

All cultivated Patescibacteria, or CPR, exist as obligate episymbionts on other microbes. Despite being ubiquitous in mammals and environmentally, molecular mechanisms of host identification and binding amongst ultrasmall bacterial episymbionts are largely unknown. Type 4 pili (T4P) are well conserved in this group and predicted to facilitate symbi...

The unique epibiotic-parasitic relationship between Nanosynbacter lyticus type strain TM7x, a member of the newly identified Candidate Phyla Radiation, now referred to as Patescibacteria, and its basibiont, Schaalia odontolytica strain XH001 (formerly Actinomyces odontolyticus), require more powerful genetic tools for deeper understanding of the ge...

Juvenile dermatomyositis (JDM) is a rare immune-mediated disease of childhood with putative links to microbial exposures. In this multi-center, prospective, observational cohort study, we evaluated whether JDM is associated with discrete oral and gut microbiome signatures. We generated 16S rRNA sequencing data from fecal, saliva, supragingival, and...

Bacteriophages (phages) play critical roles in modulating microbial ecology. Within the human microbiome, the factors influencing the long-term coexistence of phages and bacteria remain poorly investigated. Saccharibacteria (formerly TM7) are ubiquitous members of the human oral microbiome. These ultrasmall bacteria form episymbiotic relationships...

The multitude of barriers between the mouth and colon may eliminate swallowed oral bacteria. Ascertaining the presence of the same bacteria in the mouth and colon is methodologically challenging partly because 16S rRNA gene sequencing – the most commonly used method to characterize the human microbiota – has low confidence in taxonomic assignments...

Saccharibacteria (formerly TM7) are a group of widespread and genetically diverse ultrasmall bacteria with highly reduced genomes that belong to Candidate Phyla Radiation, a large monophyletic lineage with poorly understood biology. Nanosynbacter lyticus type strain TM7x is the first Saccharibacteria member isolated from the human oral microbiome....

Background Oral Saccharibacteria Nanosynbacter lyticus strain TM7× lives as an ultrasmall epibiont on the surface of its host, Schaalia odontolytica strain XH001. Establishing this interaction is a poorly understood multi-step process. The recovery phase marks a shift in the TM7×/host interaction, switching from the early killing phase, with extens...

Gut microbiota is a source of pathogens in immunocompromised patients. While most microbiota studies in patients with AML receiving induction chemotherapy have focused on the gut microbiota, the few on salivary microbiota suggest less severe dysbiosis. As the saliva does not have its own intrinsic microbiota and takes fractions of the microbiota fr...

Background Stannous fluoride dentifrice is well established for its beneficial clinical effects. In this study, we evaluated the effects of stannous fluoride on inflammation and oral microbiome. Methods In this randomized, parallel‐arm, double‐blind, controlled clinical trial, we compared clinical resolution of experimental gingivitis by evaluatin...

Variation in human immune response to the same bacterial or viral pathogen is well established in the literature. Variation in immune response to microbial challenge has also been observed within the human oral cavity. Our recent study focused on characterizing observed variations in microbially induced gingival inflammation—resulting in three dist...

Saccharibacteria (formerly TM7) Nanosynbacter lyticus type strain TM7x exhibits a remarkably compact genome and an extraordinarily small cell size. This obligate epibiotic parasite forms a symbiotic relationship with its bacterial host, Schaalia odontolytica, strain XH001 (formerly Actinomyces odontolyticus strain XH001). Due to its limited genome...

Understanding the axis of the human microbiome and physiological homeostasis is an essential task in managing deep-space-travel-associated health risks. The NASA-led Rodent Research 5 mission enabled an ancillary investigation of the gut microbiome, varying exposure to microgravity (flight) relative to ground controls in the context of previously s...

The evidence for the presence of a diverse and abundant phage population in the host-associated oral microbiome came largely from metagenomic analysis or the observation of virus-like particles within saliva/plaque samples, while the isolation of oral phage and investigation of their interaction with bacterial hosts are limited. Here, we report the...

Nanosynbacter lyticus type strain TM7x is the first cultivated member of the Saccharibacteria and the candidate phyla radiation (CPR). It was discovered to be ultrasmall in cell size with a highly reduced genome that establishes an obligate epibiotic relationship with its host bacterium.

Here, we report draft genome sequences for nine strains of “ Candidatus Nanosynbacter sp. HMT-352.” These strains and their sequences were used to interrogate strain-level variations in host range, gene content, and growth dynamics among the phylum “ Candidatus Saccharibacteria.”

Saccharibacteria (TM7), which are obligate episymbionts growing on the surface of host bacteria, may play an important role in oral disease, such as periodontitis (1, 2). As TM7 is a newly cultured lineage of bacteria, its research is limited by the small number of isolated representatives relative to the number of TM7 genomes assembled from cultur...

Saccharibacteria Nanosynbacter lyticus strain TM7x is a member of the broadly distributed Candidate Phylum Radiation. These bacteria have ultrasmall cell size, reduced genomes and live as epibionts on the surface of other bacteria. The mechanisms by which they establish and maintain this relationship are not yet fully understood. The transcriptomes...

Significance The Candidate Phyla Radiation (CPR) is a large monophyletic lineage with poorly understood biology. Saccharibacteria are ultrasmall parasitic CPR bacteria with highly reduced genomes that have made the transition from an environmental origin to mammals. We tested the function and impact of the arginine deiminase system (ADS), an argini...

Saccharibacteria (TM7) are obligate epibionts living on the surface of their host bacteria and are strongly correlated with dysbiotic microbiomes during periodontitis and other inflammatory diseases, suggesting they are putative pathogens. However, due to the recalcitrance of TM7 cultivation, causal research to investigate their role in inflammator...

Significance Experimental gingivitis studies where dental hygiene is withheld from select teeth, allowing natural bacterial accumulation, provide a unique opportunity to study the reversible transition from health to inflammatory disease in humans. Longitudinal analysis of both the microbial and host changes during human experimental gingivitis rev...

Aim: Clinically healthy gingival tissue is maintained through controlled regulation of host defense mechanisms against plaque biofilm overgrowth. One key component is the transit of neutrophils from the vasculature into gingival tissue where the expression of different neutrophil chemokines are tightly regulated. This cross-sectional study examines...

Developing a laboratory model of oral polymicrobial communities is essential for in vitro studies of the transition from healthy to diseased oral plaque. SHI-medium is an enriched growth medium capable of supporting in vitro biofilms with similar diversity to healthy supragingival inocula; however, this medium does not maintain the diversity of gra...

Strain BB001 is cultivated from the human oral cavity on its basibiont bacterial host Actinomyces sp. It is an ultrasmall bacterium with a reduced genome that grows obligately on its bacterial host. BB001 is the first member of human microbiome taxon 957.

Host range is a fundamental component of symbiotic interactions, yet it remains poorly characterized for the prevalent yet enigmatic subcategory of bacteria/bacteria symbioses. The recently characterized obligate bacterial epibiont Candidatus Nanosynbacter lyticus TM7x with its bacterial host Actinomyces odontolyticus XH001 offers an ideal system t...

The first cultivated representative of the enigmatic phylum Saccharibacteria (formerly TM7) was isolated from humans and revealed an ultra-small cell size (200–300 nm), a reduced genome with limited biosynthetic ca- pabilities, and a unique parasitic lifestyle. TM7x was the only cultivated member of the candidate phyla radi- ation (CPR), estimated...

Periodontal disease is an age-associated disorder clinically defined by periodontal bone loss, inflammation of the specialized tissues that surround and support the tooth, and microbiome dysbiosis. Currently, there is no therapy for reversing periodontal disease, and treatment is generally restricted to preventive measures or tooth extraction. The...

Periodontal disease is an age-associated disorder clinically defined by periodontal bone loss, inflammation of the specialized tissues that surround and support the tooth, and microbiome dysbiosis. Currently, there is no therapy for reversing periodontal disease, and treatment is generally restricted to preventive measures or tooth extraction. The...

Periodontal disease is an age-associated disorder clinically defined by periodontal bone loss, inflammation of the specialized tissues that surround and support the tooth, and microbiome dysbiosis. Currently, there is no therapy for reversing periodontal disease, and treatment is generally restricted to preventive measures or tooth extraction. The...

Periodontal disease is an age-associated disorder clinically defined by periodontal bone loss, inflammation of the specialized tissues that surround and support the tooth, and microbiome dysbiosis. Currently, there is no therapy for reversing periodontal disease, and treatment is generally restricted to preventive measures or tooth extraction. The...

The P. gingivalis ATCC 33277 (33277) and 381 genomes are nearly identical. However, strain 33277 displays a significantly diminished capacity to stimulate host cell TLR2-dependent signaling and IL-1β production relative to 381, suggesting that there are strain-specific differences in one or more bacterial immune-modulatory factors. Genomic sequenci...

Background: Oral gingival tissue, especially the junctional epithelium (JE), is constantly exposed to sub-gingival plaque. A key component of gingival health is the regulation of the number of neutrophils that migrate into the gingival crevice to counteract its harmful effects. This report investigates the contribution of innate defense receptors,...

Removal of one acyl chain from bacterial lipid A by deacylase activity is a mechanism used by many pathogenic bacteria to evade the host's Toll-like receptor 4 (TLR4)-mediated innate immune response. In Porphyromonas gingivalis , a periodontal pathogen, lipid A deacylase activity converts a majority of the initially synthesized penta-acylated lipid...

It is well-understood that many bacteria have evolved to survive catastrophic events using a variety of mechanisms, which include expression of stress-response genes, quiescence, necrotrophy, and metabolic advantages obtained through mutation. However, the dynamics of individuals leveraging these abilities to gain a competitive advantage in an ecol...

One of the world’s most common infectious disease, periodontitis (PD), derives from largely uncharacterized communities of oral bacteria growing as biofilms (a.k.a. plaque) on teeth and gum surfaces in periodontal pockets. Bacteria associated with periodontal disease trigger inflammatory responses in immune cells, which in later stages of the disea...

Background Dental plaque is composed of hundreds of bacterial taxonomic units and represents one of the most diverse and stable microbial ecosystems associated with the human body. Taxonomic composition and functional capacity of mature plaque is gradually shaped during several stages of community assembly via processes such as co-aggregation, com...

Significance Cultivation-independent sequencing has revealed enormous numbers of bacterial species. Amongst the most enigmatic are members of the Candidate Phyla Radiation, which are estimated to represent over 26% of all bacterial diversity. This group of ultrasmall bacteria are thought to be mostly symbionts; however, understanding these bacteria...

The ultra-small, obligate parasitic epibiont, TM7x, the first and only current member of the long-elusive Saccharibacteria (formerly the TM7 phylum) phylum to be cultivated, was isolated in co-culture with its bacterial host, Actinomyces odontolyticus subspecies actinosynbacter, XH001. Initial phenotypic characterization of the TM7x-associated XH00...

Background Recent data support the implication of accelerated titanium dissolution products in peri‐implantitis. It is unknown whether these dissolution products have an effect on the peri‐implant microbiome, the target of existing peri‐implantitis therapies. Purpose This study assessed the relationship between the peri‐implant microbiome, dissolv...

The human oral cavity is home to a large number of bacteria and bacteriophages (phages). However, the biology of oral phages as members of the human microbiome is not well understood. Recently, we isolated an Actinomyces odontolyticus subsp. Actinosynbacte r strain XH001 from human oral cavity, and genomic analysis revealed the presence of an intac...

Recently, we discovered that a member of the Saccharibacteria/TM7 phylum (strain TM7x) isolated from the human oral cavity, has an ultra-small cell size (200-300nm), a highly reduced genome (705 Kbp) with limited de novo biosynthetic capabilities, and a very novel lifestyle as an obligate epibiont on the surface of another bacterium ¹ . There has b...

A novel bacterial behavior called congregation was recently described in Shewanella oneidensis MR-1 as the accumulation of cells around insoluble electron acceptors (IEA). It is the result of a series of “run-and-reversal” events enabled by modulation of swimming speed and direction. The model proposed that the swimming cells constantly sense their...

Recent research indicates that the human microbiota play key roles in maintaining health by providing essential nutrients, providing immune education, and preventing pathogen expansion. Processes underlying the transition from a healthy human microbiome to a disease-associated microbiome are poorly understood, partially because of the potential inf...

Dental caries can be described as a dysbiosis of the oral microbial community, in which acidogenic, aciduric, and acid-adapted bacterial species promote a pathogenic environment, leading to demineralization. Alkali generation by oral microbes, specifically via arginine catabolic pathways, is an essential factor in maintaining plaque pH homeostasis....

We present here the draft genome sequence of Tannerella forsythia 9610, a clinical isolate obtained from a periodontitis patient. The genome is composed of 79 scaffolds with 82 contigs, for a length of 3,201,941 bp and a G+C of 47.3%.

Importance: In this study we show in human subjects that organophosphate pesticide exposure is associated with large-scale significant alterations of the oral buccal microbiota composition with extinctions of whole genera suggested in some individuals. Persistence from the spring/summer to the winter of this association also suggests long lasting...

Analyses of metagenome data (MG) and metatranscriptome data (MT) are often challenged by a paucity of complete reference genome sequences and the uneven/low sequencing depth of the constituent organisms in the microbial community, which respectively limit the power of reference-based alignment and de novo sequence assembly. These limitations make a...

Accession numbers for the human oral metatranscriptomic data set SRP049210 that were selected for the differential expression and targeted assembly experiments. (XLSX)

Taxonomic composition of the simulated marine data set. (XLSX)

The Pfam families that were selected as the queries for the benchmark experiment on the simulated marine data set. (XLSX)

The N50 for the contigs that were assembled by SFA-SPA using the HMM-GRASPx-, HMMER3-, RPS-BLAST-, and UProC-predicted homolog reads from the human saliva data set SRS013942. (XLSX)

Running time for each program on searching against the simulated marine data set. (XLSX)

Running time for each program on searching against the human saliva data set SRS013942. (XLSX)

The two-dimensional hierarchical clustering results generated by using the HMMER3-predicted AMR families abundance profiles for the human supragingival and stool data sets. (PDF)

The Pfam families that were selected as the queries for the benchmark experiment on the human saliva data set SRS013942. (XLSX)

Accession numbers for the human supragingival and stool metagenomic data sets that were selected for the AMR protein family profiling experiment. (XLSX)

The antiSMASH2.0 profile HMMs that were chosen for the differential expression and targeted assembly experiments on the human oral metatranscriptomic data set SRP049210. (XLSX)

Benchmark results of HMM-GRASPx, HMMER3, RPS-BLAST, and UProC on a simulated data set where every single genome (the 23 genomes in use is listed in S1 Table) has an even 10X coverage. (XLSX)