Ecology of the Oral Microbiome: Beyond Bacteria Baker, Jonathon L; Bor, Batbileg; Agnello, Melissa ...
Trends in microbiology (Regular ed.),
05/2017, Letnik:
25, Številka:
5
Journal Article
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Although great strides have been made in understanding the complex bacterial community inhabiting the human oral cavity, for a variety of (mainly technical) reasons the ecological contributions of ...oral fungi, viruses, phages, and the candidate phyla radiation (CPR) group of ultrasmall bacteria have remained understudied. Several recent reports have illustrated the diversity and importance of these organisms in the oral cavity, while TM7x and Candida albicans have served as crucial paradigms for CPR species and oral fungi, respectively. A comprehensive understanding of the oral microbiota and its influence on host health and disease will require a holistic view that emphasizes interactions among different residents within the oral community, as well as their interaction with the host.
Human influenza viruses replicate almost exclusively in the respiratory tract, yet infected individuals may also develop gastrointestinal symptoms, such as vomiting and diarrhea. However, the ...molecular mechanisms remain incompletely defined. Using an influenza mouse model, we found that influenza pulmonary infection can significantly alter the intestinal microbiota profile through a mechanism dependent on type I interferons (IFN-Is). Notably, influenza-induced IFN-Is produced in the lungs promote the depletion of obligate anaerobic bacteria and the enrichment of Proteobacteria in the gut, leading to a "dysbiotic" microenvironment. Additionally, we provide evidence that IFN-Is induced in the lungs during influenza pulmonary infection inhibit the antimicrobial and inflammatory responses in the gut during Salmonella-induced colitis, further enhancing Salmonella intestinal colonization and systemic dissemination. Thus, our studies demonstrate a systemic role for IFN-Is in regulating the host immune response in the gut during Salmonella-induced colitis and in altering the intestinal microbial balance after influenza infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The candidate phylum TM7 is globally distributed and often associated with human inflammatory mucosal diseases. Despite its prevalence, the TM7 phylum remains recalcitrant to cultivation, making it ...one of the most enigmatic phyla known. In this study, we cultivated a TM7 phylotype (TM7x) from the human oral cavity. This extremely small coccus (200–300 nm) has a distinctive lifestyle not previously observed in human-associated microbes. It is an obligate epibiont of anActinomyces odontolyticusstrain (XH001) yet also has a parasitic phase, thereby killing its host. This first completed genome (705 kb) for a human-associated TM7 phylotype revealed a complete lack of amino acid biosynthetic capacity. Comparative genomics analyses with uncultivated environmental TM7 assemblies show remarkable conserved gene synteny and only minimal gene loss/gain that may have occurred as TM7x adapted to conditions within the human host. Transcriptomic and metabolomic profiles provided the first indications, to our knowledge, that there is signaling interaction between TM7x and XH001. Furthermore, the induction of TNF-α production in macrophages by XH001 was repressed in the presence of TM7x, suggesting its potential immune suppression ability. Overall, our data provide intriguing insights into the uncultivability, pathogenicity, and unique lifestyle of this previously uncharacterized oral TM7 phylotype.
With the emergence of multidrug-resistant and extensively drug-resistant bacterial pathogens, phage therapy and other alternative or additional therapeutic modalities are receiving resurgent ...attention. One of the major obstacles in developing effective phage therapies is the evolution of phage resistance in the bacterial host. When
was infected with a phage that uses O-antigen as receptor, phage resistances typically achieved through changing or loss of O-antigen structure. In this study, we showed that dsRNA phage phiYY uses core lipopolysaccharide as receptor and therefore efficiently kills the O-antigen deletion mutants. Furthermore, by phage training, we obtained PaoP5-m1, a derivative of dsDNA phage PaoP5, which is able to infect mutants with truncated O-antigen. We then generated a cocktail by mixing phiYY and PaoP5-m1 with additional three wide host range
phages. The phage cocktail was effective against a diverse selection of clinical isolates of
, and in the short-term constrained the appearance of the phage-resistant mutants that had beleaguered the effectiveness of single phage. Resistance to the 5-phage cocktail emerges after several days, and requires mutations in both
and
Thus, this study provides an alternative strategy for designing phage cocktail and phage therapy.
Candida albicans and Fusobacterium nucleatum are well-studied oral commensal microbes with pathogenic potential that are involved in various oral polymicrobial infectious diseases. Recently, we ...demonstrated that F. nucleatum ATCC 23726 coaggregates with C. albicans SN152, a process mainly mediated by fusobacterial membrane protein RadD and Candida cell wall protein Flo9. The aim of this study was to investigate the potential biological impact of this inter-kingdom interaction. We found that F. nucleatum ATCC 23726 inhibits growth and hyphal morphogenesis of C. albicans SN152 in a contact-dependent manner. Further analysis revealed that the inhibition of Candida hyphal morphogenesis is mediated via RadD and Flo9 protein pair. Using a murine macrophage cell line, we showed that the F. nucleatum-induced inhibition of Candida hyphal morphogenesis promotes C. albicans survival and negatively impacts the macrophage-killing capability of C. albicans. Furthermore, the yeast form of C. albicans repressed F. nucleatum-induced MCP-1 and TNFα production in macrophages. Our study suggests that the interaction between C. albicans and F. nucleatum leads to a mutual attenuation of virulence, which may function to promote a long-term commensal lifestyle within the oral cavity. This finding has significant implications for our understanding of inter-kingdom interaction and may impact clinical treatment strategies.
One major challenge to studying human microbiome and its associated diseases is the lack of effective tools to achieve targeted modulation of individual species and study its ecological function ...within multispecies communities. Here, we show that C16G2, a specifically targeted antimicrobial peptide, was able to selectively kill cariogenic pathogen Streptococcus mutans with high efficacy within a human saliva-derived in vitro oral multispecies community. Importantly, a significant shift in the overall microbial structure of the C16G2-treated community was revealed after a 24-h recovery period: several bacterial species with metabolic dependency or physical interactions with S. mutans suffered drastic reduction in their abundance, whereas S. mutans â natural competitors, including health-associated Streptococci, became dominant. This study demonstrates the use of targeted antimicrobials to modulate the microbiome structure allowing insights into the key community role of specific bacterial species and also indicates the therapeutic potential of C16G2 to achieve a healthy oral microbiome.
Significance The lack of effective tools to modulate individual species within a complex microbial community poses a major barrier to studying human microbiome and its associated diseases. We showed targeted removal of human cariogenic Streptococcus mutans within an in vitro oral multispecies community using a high-efficacy antimicrobial peptideâC16G2âas well as drastic reconstruction of the microbial structure following treatment. The findings suggest the potential of using targeted antimicrobials to modulate microbiome and study the ecological function of specific bacterial species.
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 capabilities, and a unique parasitic lifestyle. TM7x was the only cultivated member of the candidate phyla radiation (CPR), estimated to encompass 26% of the domain Bacteria. Here we report on divergent genomes from major lineages across the Saccharibacteria phylum in humans and mammals, as well as from ancient dental calculus. These lineages are present at high prevalence within hosts. Direct imaging reveals that all groups are ultra-small in size, likely feeding off commensal bacteria. Analyses suggest that multiple acquisition events in the past led to the current wide diversity, with convergent evolution of key functions allowing Saccharibacteria from the environment to adapt to mammals. Ultra-small, parasitic CPR bacteria represent a relatively unexplored paradigm of prokaryotic interactions within mammalian microbiomes.
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•Saccharibacteria are ultra-small parasitic bacteria recently discovered in humans•Novel lineages have high genomic diversity within mammalian hosts•Novel lineages are ultra-small, with reduced genomes (<1,000 genes) and a single 16S copy•One group displays minimal genomic changes since transition from environment to humans
McLean et al. show that humans are inhabited by a broad diversity of nano-sized bacteria with highly reduced genomes within the Saccharibacteria phylum. They are related to the candidate phyla radiation predominately found in the environment. Saccharibacteria show adaptations and diversification in mammals during their transition from the environment.
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 inflammatory diseases is lacking. Here, we isolated multiple TM7 species on their host bacteria from periodontitis patients. These TM7 species reduce inflammation and consequential bone loss by modulating host bacterial pathogenicity in a mouse ligature-induced periodontitis model. Two host bacterial functions involved in collagen binding and utilization of eukaryotic sialic acid are required for inducing bone loss and are altered by TM7 association. This TM7-mediated downregulation of host bacterial pathogenicity is shown for multiple TM7/host bacteria pairs, suggesting that, in contrast to their suspected pathogenic role, TM7 could protect mammalian hosts from inflammatory damage induced by their host bacteria.
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•Saccharibacteria (TM7) is an epibiont that lives on the surface of Actinobacteria•Multiple TM7 isolates from periodontitis patients decrease inflammatory bone loss•TM7 reduce bone loss by modulating the pathogenicity of their host Actinobacteria•TM7 could serve a protective role for mammalian hosts in inflammatory diseases
If certain bacteria are increased in disease, does that mean they are bad? Chipashvili et al. show that this may not be the case for ultrasmall Saccharibacteria. By using a mouse model for periodontitis, they determined that Saccharibacteria offer protection by reducing the pathogenicity of other bacteria in inflammatory diseases.
Ferroptosis is a form of regulated cell death (RCD) characterized by iron-dependent lipid peroxidation. Ferroptosis is currently proposed as one of the most promising means of combating tumor ...resistance. Nevertheless, the problem of ferroptosis resistance in certain cancer cells has been identified. This review first, investigates the mechanisms of ferroptosis induction in cancer cells. Next, the problem of cancer cell resistance to ferroptosis, as well as the underlying mechanisms is discussed. Recently discovered ferroptosis-suppressing biomarkers have been described. The various types of nanoparticles that can induce ferroptosis are also discussed. Given the ability of nanoparticles to combine multiple agents, this review proposes nanoparticle-based ferroptosis cell death as a viable method of circumventing this resistance. This review suggests combining ferroptosis with other forms of cell death, such as apoptosis, cuproptosis and autophagy. It also suggests combining ferroptosis with immunotherapy.
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