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Bacterial secretion of D-arginine controls environmental microbial biodiversity
Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
2018 (Engelska)Ingår i: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 12, nr 2, s. 438-450Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Bacteria face tough competition in polymicrobial communities. To persist in a specific niche, many species produce toxic extracellular effectors to interfere with the growth of nearby microbes. These effectors include the recently reported non-canonical D-amino acids (NCDAAs). In Vibrio cholerae, the causative agent of cholera, NCDAAs control cell wall integrity in stationary phase. Here, an analysis of the composition of the extracellular medium of V. cholerae revealed the unprecedented presence of D-Arg. Compared with other D-amino acids, D-Arg displayed higher potency and broader toxicity in terms of the number of bacterial species affected. Tolerance to D-Arg was associated with mutations in the phosphate transport and chaperone systems, whereas D-Met lethality was suppressed by mutations in cell wall determinants. These observations suggest that NCDAAs target different cellular processes. Finally, even though virtually all Vibrio species are tolerant to D-Arg, only a few can produce this D-amino acid. Indeed, we demonstrate that D-Arg may function as part of a cooperative strategy in vibrio communities to protect non-producing members from competing bacteria. Because NCDAA production is widespread in bacteria, we anticipate that D-Arg is a relevant modulator of microbial subpopulations in diverse ecosystems.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2018. Vol. 12, nr 2, s. 438-450
Nationell ämneskategori
Medicinsk bioteknologi
Identifikatorer
URN: urn:nbn:se:umu:diva-144335DOI: 10.1038/ismej.2017.176ISI: 000422779100013PubMedID: 29028003Scopus ID: 2-s2.0-85040816195OAI: oai:DiVA.org:umu-144335DiVA, id: diva2:1181460
Forskningsfinansiär
Knut och Alice Wallenbergs StiftelseVetenskapsrådetKempestiftelsernaTillgänglig från: 2018-02-08 Skapad: 2018-02-08 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
Ingår i avhandling
1. Molecular mechanisms and biological consequences of the production of non-canonical D-amino acids in bacteria
Öppna denna publikation i ny flik eller fönster >>Molecular mechanisms and biological consequences of the production of non-canonical D-amino acids in bacteria
2021 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Most bacteria possess a vital net-like macromolecule – peptidoglycan (PG). PG encases bacteria around the cytoplasmic membrane to withstand the high internal turgor pressure and thereby protect the cell from bursting. In addition, PG is a major morphological determinant of bacteria being both required and sufficient to maintain cell shape. During cell growth PG hydrolysis and synthesis are tightly controlled to keep proper cell shape and integrity at all times. Given the essentiality of PG for bacterial growth and survival, the synthesis of this polymer is a major target of many natural and synthetic antibiotics (e.g. penicillins, glycopeptides).

For a long time, PG composition was considered to be conserved and static, however it’s now being recognized as a dynamic and plastic macromolecule. The structure and chemistry of PG is influenced by a myriad of environmental cues that include interkingdom/interspecies interactions. Recently, it was found that a wide set of non-canonical D-amino acids (D-amino acids different from D-Ala and D-Glu, NCDAAs) are produced and released to the extracellular milieu by diverse bacteria. In Vibrio cholerae these NCDAAs are produced by broad-spectrum racemase enzyme (BsrV) and negatively regulate PG synthesis through their incorporation into PG. We have shown that in addition to D-Met and D-Leu, which were reported previously, V. cholerae also releases high amounts of D-Arg, which inhibits a broader range of phylogenetically diverse bacteria. Thus, NCDAAs affect not only the producer, but might target other species within the same environmental niche. However, in contrast to D-Met, D-Arg targets cell wall independent pathways. 

We have shown that non-proteinogenic amino acids also can be racemized by Bsr. A plant amino acid L-canavanine (L-CAN) is converted into D-CAN by a broad-spectrum amino acid racemase (BSAR) of the soil bacterium Pseudomonas putida and subsequently released to the environment. D-CAN gets highly incorporated into the PG of Rhizobiales (such as Agrobacterium tumefaciens, Sinorhizobium meliloti) thereby affecting the overall PG structure, bacterial morphogenesis and growth fitness. We found that detrimental effect of D-CAN in A. tumefaciens can be suppressed by a single amino acid substitution in the cell division PG transpeptidase penicillin-binding protein 3a (PBP3a). 

Rhizobiales are a polar-growing species that encode multiple LD-transpeptidases (LDTs), enzymes that normally perform PG crosslinking, but that can also incorporate NCDAAs into termini of the PG peptides. As these species incorporate high amounts of D-CAN in their PG, we hypothesized that LDTs might represent the main path used by NCDAAs to edit A. tumefaciens’ PG and cause their detrimental effects. Therefore, we decided to further explore the significance of LDT proteins for growth and morphogenesis in A. tumefaciens. While in the Gram-negative model organism E. coli LDT proteins are non-essential under standard laboratory conditions, we found that A. tumefaciens needs at least one LDT for growth out of the 14 putative LDTs encoded in its genome. Moreover, clustering the LDT proteins based on their sequence similarity revealed that A. tumefaciens has 7 LDTs that are exclusively present among Rhizobiales. Interestingly, the loss of this group of LDTs (but not the rest) leads to reduced growth, lower PG crosslinkage and rounded cell phenotype, which suggests that this group of Rhizobiales- specific LDTs have a major role in maintaining LD-crosslinking homeostasis, which in turn is important for cell elongation and proper shape maintenance in A. tumefaciens.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2021. s. 59
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 2139
Nyckelord
Bacteria, cell wall, peptidoglycan, D-amino acids, LD-transpeptidase
Nationell ämneskategori
Mikrobiologi
Identifikatorer
urn:nbn:se:umu:diva-182615 (URN)978-91-7855-557-4 (ISBN)978-91-7855-556-7 (ISBN)
Disputation
2021-05-21, Thymine/Uracil, Institutionen för molekylärbiologi, Umeå, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2021-04-30 Skapad: 2021-04-27 Senast uppdaterad: 2021-04-28Bibliografiskt granskad

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Alvarez, LauraAliashkevich, AlenaCava, Felipe

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Molekylär Infektionsmedicin, Sverige (MIMS)Umeå Centre for Microbial Research (UCMR)Institutionen för molekylärbiologi (Medicinska fakulteten)
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