Interplay between microbial d-amino acids and host d-amino acid oxidase modifies murine mucosal defence and gut microbiota

Sasabe, Jumpei; Miyoshi, Y.; Rakoff-Nahoum, Seth; Zhang, Ting; Mita, Masashi; Davis, Brigid M.; Hamase, Kenji; Waldor, Matthew K.

doi:10.1038/nmicrobiol.2016.125

Cited by 168 publications

(222 citation statements)

References 47 publications

Supporting

Mentioning

200

Contrasting

Order By: Relevance

“…We developed a colorimetric assay using the D-Lys-specific oxidase AmaD from Pseudomonas putida to detect and quantify the concentration of D-Lys in culture supernatants of Ab17978 ( Figure 2A) (23). Using our AmaD assay, we determined that Ab17978 produces and secretes D-Lys into culture supernatants to a concentration of ~0.3 mM ( Figure 2B), which is comparable to levels of NCDAA secreted by other bacterial species (19,24). D-Lys secretion has not been reported in Acinetobacter leading us to investigate how D-Lys is produced.…”

mentioning

confidence: 75%

“…Unexpectedly, strains unable to produce D-Lys showed significantly higher bacterial burdens (1 to 2 log CFU) in the kidney, heart and liver, suggesting that D-Lys production is disadvantageous for bacterial dissemination ( Figure 4A). Recent findings have suggested that the D-amino acid oxidase (DAO), expressed by human neutrophils, macrophages and epithelial cells, contributes to host defense against various pathogens through the production of H2O2, a by-product of the DAO-dependent oxidative deamination of D-amino acids (24,35,36). Thus, we hypothesized that D-Lys-producing bacteria would be more susceptible to DAO-dependent killing.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Peptidoglycan editing provides immunity toAcinetobacter baumanniiduring bacterial warfare

Le¹,

Peters

Espaillat

et al. 2020

Preprint

View full text Add to dashboard Cite

Peptidoglycan (PG) is essential in most bacteria. Thus, it is often targeted by various assaults, including the host immune response, antibiotic treatment and interbacterial attacks via the type VI secretion system (T6SS). Here, we report that the Gram-negative bacterium Acinetobacter baumannii strain ATCC 17978 produces, secretes and incorporates the non-canonical D-amino acid D-Lysine into its PG during stationary phase. We show that PG editing increases the competitiveness of A. baumannii during bacterial warfare by providing immunity against peptidoglycan-targeting T6SS effectors from various bacterial competitors. We propose that PG editing has evolved as an effective strategy for bacteria to overcome T6SS attacks. In contrast, we found that D-Lys production is detrimental to pathogenesis due, at least in part, to the activity of the human enzyme D-amino acid oxidase (DAO), which degrades D-Lys producing H2O2 toxic to bacteria. Phylogenetic analyses indicate that the last common ancestor of A. baumannii possessed the ability to produce D-Lys. However, this trait was independently lost multiple times, likely reflecting the evolution of A. baumannii as a human pathogen. One sentence summary:Acinetobacter baumannii attains immunity against nonkin competitors during T6SS warfare by incorporating D-Lysine into its peptidoglycan. Main Text:Peptidoglycan (PG) is a major component of the bacterial cell envelope. Layers of PG surround the cytoplasmic membrane, maintaining cell shape and providing resistance to osmotic stress. PG is composed of glycan chains of alternating N-acetylglucosamine (GlcNAc) and Nacetylmuramic acid (MurNAc) that are connected through MurNAc-attached peptides (1). Despite its rigidity, PG is necessarily a dynamic structure, requiring constant turnover to enable fundamental processes such as growth and cell division (2). PG synthesis is a multi-step process.The PG precursor lipid II, which consists of a GlcNAc-MurNAc pentapeptide (L-Ala-D-iGlu-mDAP-D-Ala-D-Ala in Gram-negative bacteria) linked to a lipid carrier, is synthesized at the cytoplasmic membrane and subsequently translocated into the outer leaflet of the cytoplasmic membrane.Glycan chains are then polymerized by glycosyltransferases and peptide cross-links are formed through transpeptidation reactions catalyzed by DD-transpeptidases and LD-transpeptidases.

show abstract

mentioning

confidence: 75%

mentioning

confidence: 99%

Peptidoglycan editing provides immunity toAcinetobacter baumanniiduring bacterial warfare

Le¹,

Peters

Espaillat

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…This enzyme may also have greater implications in coral host-microbiome interactions. Beneficial holobiont bacteria have been shown to have resistance to host DAO while also being able to manage levels through the TLR-to-NF-kappa-B pathway [95]. We therefore hypothesize that DAO could have a dual role in A. palmata as it is important in the immune response, as well as maintaining symbiosis with coral microbial partners as in other organisms [95] with future research needed to characterize its role.…”

Section: Discussionmentioning

confidence: 99%

Innate immune gene expression inAcropora palmatais consistent despite variance in yearly disease events

Young

Serrano

Rosales

et al. 2020

Preprint

View full text Add to dashboard Cite

Coral disease outbreaks are expected to increase in prevalence, frequency and severity due to climate change and other anthropogenic stressors. This is especially worrying for the Caribbean branching Acropora palmata which has already seen an 80% decrease in its coral cover, with this primarily due to disease. Despite the importance of this species, there has yet to be a characterization of its transcriptomic response to disease exposure. In this study we provide the first transcriptomic analysis of 12 A. palmata genotypes, and their symbiont Symbiodiniaceae, exposed to disease in 2016 and 2017. Year was the primary driver of sample variance for A. palmata and the Symbiodiniaceae. Lower expression of ribosomal genes in the coral, and higher expression of transmembrane ion transport genes in the Symbiodiniaceae indicate that the increased virulence in 2017 may have been due to a dysbiosis between the coral and Symbiodiniaceae. We also identified a conserved suite of innate immune genes responding to the disease challenge that was activated in both years. This included genes from the Toll-like receptor and lectin pathways, and antimicrobial peptides. Co-expression analysis identified a module positively correlated to disease exposure rich in innate immune genes, with D-amino acid oxidase, a gene implicated in phagocytosis and microbiome homeostasis, as the hub gene. The role of D-amino acid oxidase in coral immunity has not been characterized but holds potential as an important enzyme for responding to disease. Our results indicate that A. palmata mounts a similar immune response to disease exposure as other coral species previously studied, but with unique features that may be critical to the survival of this keystone Caribbean species.

show abstract

“…Many further genes are certainly involved in protection against AGE formation and degradation [in particular managing aldehyde oxidation, see for example the role of aldehyde dehydrogenase ADH1B and ADH2 located in the human throat (Salaspuro, ; Guo et al ., ), and deglycation], but I will retain here only one final process, that will allow us to connect with what happens in the gut: we have previously seen that cooking tends to racemize amino acids. Remarkably, a d ‐amino acid oxidase is secreted in the lumen of the gut in mice (Sasabe et al ., ). Whether a counterpart in man also exists and is submitted to positive selection would be of considerable interest, noting again that several neuromediators are d ‐amino acids ( d ‐ser and d ‐asp).…”

Section: The Taming Of Fire and Its Consequencesmentioning

confidence: 97%

Bacteria in the ageing gut: did the taming of fire promote a long human lifespan?

Danchin

2018

Environmental Microbiology

View full text Add to dashboard Cite

Unique among animals as they evolved towards Homo sapiens, hominins progressively cooked their food on a routine basis. Cooked products are characterized by singular chemical compounds, derived from the pervasive Maillard reaction. This same reaction is omnipresent in normal metabolism involving carbonyls and amines, and its products accumulate with age. The gut microbiota acts as a first line of defence against the toxicity of cooked Maillard compounds, that also selectively shape the microbial flora, letting specific metabolites to reach the blood stream. Positive selection of metabolic functions allowed the body of hominins who tamed fire to use and dispose of these age-related compounds. I propose here that, as a hopeful accidental consequence, this resulted in extending human lifespan far beyond that of our great ape cousins. The limited data exploring the role of taming fire on the human genetic setup and on its microbiota is discussed in relation with ageing.

show abstract

Interplay between microbial d-amino acids and host d-amino acid oxidase modifies murine mucosal defence and gut microbiota

Cited by 168 publications

References 47 publications

Peptidoglycan editing provides immunity toAcinetobacter baumanniiduring bacterial warfare

Peptidoglycan editing provides immunity toAcinetobacter baumanniiduring bacterial warfare

Innate immune gene expression inAcropora palmatais consistent despite variance in yearly disease events

Bacteria in the ageing gut: did the taming of fire promote a long human lifespan?

Contact Info

Product

Resources

About