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  1. Book ; Online: Bacterial Cell Wall Structure and Dynamics

    Dörr, Tobias / Dörr, Tobias / Moynihan, Partick J. / Mayer, Christoph

    2019  

    Keywords Science: general issues ; Medical microbiology & virology ; Microbiology (non-medical) ; bacterial cell wall ; peptidoglycan synthesis ; cell wall dynamics ; cell wall turnover ; cell wall modification ; peptidoglycan recycling ; autolysins ; cell wall degradation ; antibiotic target
    Size 1 electronic resource (199 pages)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021230799
    ISBN 9782889631520 ; 2889631524
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: Cleave a Septum, Leave a Cell: Bdellovibrio bacteriovorus Secretes a Specialized Lytic Transglycosylase to Clear Prey Cell Septum Obstruction.

    Dörr, Tobias

    Journal of bacteriology

    2023  Volume 205, Issue 4, Page(s) e0007423

    Abstract: Predatory microbes ... ...

    Abstract Predatory microbes like
    MeSH term(s) Bdellovibrio bacteriovorus/genetics ; Bdellovibrio
    Language English
    Publishing date 2023-04-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2968-3
    ISSN 1098-5530 ; 0021-9193
    ISSN (online) 1098-5530
    ISSN 0021-9193
    DOI 10.1128/jb.00074-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Bacterial physiology: A novel periplasmic glucan promotes cell envelope stress management.

    Dörr, Tobias

    Current biology : CB

    2023  Volume 33, Issue 2, Page(s) R65–R67

    Abstract: A newly discovered pathway relying on the production and modification of periplasmic oligosaccharides is required for proper cell-envelope homeostasis and antibiotic resistance in Gram-negative bacteria. ...

    Abstract A newly discovered pathway relying on the production and modification of periplasmic oligosaccharides is required for proper cell-envelope homeostasis and antibiotic resistance in Gram-negative bacteria.
    MeSH term(s) Glucans/metabolism ; Cell Membrane/metabolism ; Cell Wall/metabolism ; Gram-Negative Bacteria ; Bacterial Physiological Phenomena ; Bacterial Proteins/metabolism
    Chemical Substances Glucans ; Bacterial Proteins
    Language English
    Publishing date 2023-03-01
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2022.11.069
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Understanding tolerance to cell wall-active antibiotics.

    Dörr, Tobias

    Annals of the New York Academy of Sciences

    2020  Volume 1496, Issue 1, Page(s) 35–58

    Abstract: Antibiotic tolerance-the ability of bacteria to survive for an extended time in the presence of bactericidal antibiotics-is an understudied contributor to antibiotic treatment failure. Herein, I review the manifestations, mechanisms, and clinical ... ...

    Abstract Antibiotic tolerance-the ability of bacteria to survive for an extended time in the presence of bactericidal antibiotics-is an understudied contributor to antibiotic treatment failure. Herein, I review the manifestations, mechanisms, and clinical relevance of tolerance to cell wall-active (CWA) antibiotics, one of the most important groups of antibiotics at the forefront of clinical use. I discuss definitions of tolerance and assays for tolerance detection, comprehensively discuss the mechanism of action of β-lactams and other CWA antibiotics, and then provide an overview of how cells mitigate the potentially lethal effects of CWA antibiotic-induced cell damage to become tolerant. Lastly, I discuss evidence for a role of CWA antibiotic tolerance in clinical antibiotic treatment failure.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Cell Wall/drug effects ; Microbial Sensitivity Tests
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2020-12-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/nyas.14541
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Novel role for peptidoglycan carboxypeptidases in maintaining the balance between bacterial cell wall synthesis and degradation.

    Obando, Manuela Alvarado / Dörr, Tobias

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Peptidoglycan (PG) is the main component of the bacterial cell wall; it maintains cell shape while protecting the cell from internal osmotic pressure and external environmental challenges. PG synthesis is essential for bacterial growth and survival, and ... ...

    Abstract Peptidoglycan (PG) is the main component of the bacterial cell wall; it maintains cell shape while protecting the cell from internal osmotic pressure and external environmental challenges. PG synthesis is essential for bacterial growth and survival, and a series of PG modifications are required to allow expansion of the sacculus. Endopeptidases (EPs), for example, cleave the crosslinks between adjacent PG strands to allow the incorporation of newly synthesized PG. EPs are collectively essential for bacterial growth and must likely be carefully regulated to prevent sacculus degradation and cell death. However, EP regulation mechanisms are poorly understood. Here, we used TnSeq to uncover novel EP regulation factors in
    Language English
    Publishing date 2023-07-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.12.548665
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Bacterial metabolism and susceptibility to cell wall-active antibiotics.

    Keller, Megan Renee / Dörr, Tobias

    Advances in microbial physiology

    2023  Volume 83, Page(s) 181–219

    Abstract: Bacterial infections are increasingly resistant to antimicrobial therapy. Intense research focus has thus been placed on identifying the mechanisms that bacteria use to resist killing or growth inhibition by antibiotics and the ways in which bacteria ... ...

    Abstract Bacterial infections are increasingly resistant to antimicrobial therapy. Intense research focus has thus been placed on identifying the mechanisms that bacteria use to resist killing or growth inhibition by antibiotics and the ways in which bacteria share these traits with one another. This work has led to the advancement of new drugs, combination therapy regimens, and a deeper appreciation for the adaptability seen in microorganisms. However, while the primary mechanisms of action of most antibiotics are well understood, the more subtle contributions of bacterial metabolic state to repairing or preventing damage caused by antimicrobials (thereby promoting survival) are still understudied. Here, we review a modern viewpoint on a classical system: examining bacterial metabolism's connection to antibiotic susceptibility. We dive into the relationship between metabolism and antibiotic efficacy through the lens of growth rate, energy state, resource allocation, and the infection environment, focusing on cell wall-active antibiotics.
    MeSH term(s) Humans ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/metabolism ; Bacteria/metabolism ; Anti-Infective Agents/metabolism ; Bacterial Infections/drug therapy ; Cell Wall/metabolism
    Chemical Substances Anti-Bacterial Agents ; Anti-Infective Agents
    Language English
    Publishing date 2023-05-16
    Publishing country England
    Document type Review ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 174-0
    ISSN 2162-5468 ; 0065-2911
    ISSN (online) 2162-5468
    ISSN 0065-2911
    DOI 10.1016/bs.ampbs.2023.04.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Genetic interaction mapping reveals functional relationships between peptidoglycan endopeptidases and carboxypeptidases.

    Alvarado Obando, Manuela / Rey-Varela, Diego / Cava, Felipe / Dörr, Tobias

    PLoS genetics

    2024  Volume 20, Issue 4, Page(s) e1011234

    Abstract: Peptidoglycan (PG) is the main component of the bacterial cell wall; it maintains cell shape while protecting the cell from internal osmotic pressure and external environmental challenges. PG synthesis is essential for bacterial growth and survival, and ... ...

    Abstract Peptidoglycan (PG) is the main component of the bacterial cell wall; it maintains cell shape while protecting the cell from internal osmotic pressure and external environmental challenges. PG synthesis is essential for bacterial growth and survival, and a series of PG modifications are required to allow expansion of the sacculus. Endopeptidases (EPs), for example, cleave the crosslinks between adjacent PG strands to allow the incorporation of newly synthesized PG. EPs are collectively essential for bacterial growth and must likely be carefully regulated to prevent sacculus degradation and cell death. However, EP regulation mechanisms are poorly understood. Here, we used TnSeq to uncover novel EP regulators in Vibrio cholerae. This screen revealed that the carboxypeptidase DacA1 (PBP5) alleviates EP toxicity. dacA1 is essential for viability on LB medium, and this essentiality was suppressed by EP overexpression, revealing that EP toxicity both mitigates, and is mitigated by, a defect in dacA1. A subsequent suppressor screen to restore viability of ΔdacA1 in LB medium identified hypomorphic mutants in the PG synthesis pathway, as well as mutations that promote EP activation. Our data thus reveal a more complex role of DacA1 in maintaining PG homeostasis than previously assumed.
    MeSH term(s) Peptidoglycan/metabolism ; Vibrio cholerae/genetics ; Vibrio cholerae/metabolism ; Endopeptidases/genetics ; Endopeptidases/metabolism ; Carboxypeptidases/genetics ; Carboxypeptidases/metabolism ; Cell Wall/metabolism ; Cell Wall/genetics ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Gene Expression Regulation, Bacterial ; Epistasis, Genetic ; Mutation
    Chemical Substances Peptidoglycan ; Endopeptidases (EC 3.4.-) ; peptidoglycan endopeptidase ; Carboxypeptidases (EC 3.4.-) ; Bacterial Proteins
    Language English
    Publishing date 2024-04-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1011234
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Masters of Misdirection: Peptidoglycan Glycosidases in Bacterial Growth.

    Weaver, Anna / Taguchi, Atsushi / Dörr, Tobias

    Journal of bacteriology

    2023  Volume 205, Issue 3, Page(s) e0042822

    Abstract: The dynamic composition of the peptidoglycan cell wall has been the subject of intense research for decades, yet how bacteria coordinate the synthesis of new peptidoglycan with the turnover and remodeling of existing peptidoglycan remains elusive. ... ...

    Abstract The dynamic composition of the peptidoglycan cell wall has been the subject of intense research for decades, yet how bacteria coordinate the synthesis of new peptidoglycan with the turnover and remodeling of existing peptidoglycan remains elusive. Diversity and redundancy within peptidoglycan synthases and peptidoglycan autolysins, enzymes that degrade peptidoglycan, have often made it challenging to assign physiological roles to individual enzymes and determine how those activities are regulated. For these reasons, peptidoglycan glycosidases, which cleave within the glycan strands of peptidoglycan, have proven veritable masters of misdirection over the years. Unlike many of the broadly conserved peptidoglycan synthetic complexes, diverse bacteria can employ unrelated glycosidases to achieve the same physiological outcome. Additionally, although the mechanisms of action for many individual enzymes have been characterized, apparent conserved homologs in other organisms can exhibit an entirely different biochemistry. This flexibility has been recently demonstrated in the context of three functions critical to vegetative growth: (i) release of newly synthesized peptidoglycan strands from their membrane anchors, (ii) processing of peptidoglycan turned over during cell wall expansion, and (iii) removal of peptidoglycan fragments that interfere with daughter cell separation during cell division. Finally, the regulation of glycosidase activity during these cell processes may be a cumulation of many factors, including protein-protein interactions, intrinsic substrate preferences, substrate availability, and subcellular localization. Understanding the true scope of peptidoglycan glycosidase activity will require the exploration of enzymes from diverse organisms with equally diverse growth and division strategies.
    MeSH term(s) Glycoside Hydrolases/genetics ; Glycoside Hydrolases/metabolism ; Peptidoglycan/metabolism ; Bacteria/metabolism ; Cell Wall/metabolism ; Cell Division ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism
    Chemical Substances Glycoside Hydrolases (EC 3.2.1.-) ; Peptidoglycan ; Bacterial Proteins
    Language English
    Publishing date 2023-02-09
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2968-3
    ISSN 1098-5530 ; 0021-9193
    ISSN (online) 1098-5530
    ISSN 0021-9193
    DOI 10.1128/jb.00428-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Disrupting Central Carbon Metabolism Increases β-Lactam Antibiotic Susceptibility in Vibrio cholerae.

    Keller, Megan / Han, Xiang / Dörr, Tobias

    Journal of bacteriology

    2023  Volume 205, Issue 3, Page(s) e0047622

    Abstract: Antibiotic tolerance, the ability of bacteria to sustain viability in the presence of typically bactericidal antibiotics for extended time periods, is an understudied contributor to treatment failure. The Gram-negative pathogen Vibrio cholerae, the ... ...

    Abstract Antibiotic tolerance, the ability of bacteria to sustain viability in the presence of typically bactericidal antibiotics for extended time periods, is an understudied contributor to treatment failure. The Gram-negative pathogen Vibrio cholerae, the causative agent of cholera, becomes highly tolerant to β-lactam antibiotics (penicillin and related compounds) in a process requiring the two-component system VxrAB. VxrAB is induced by exposure to cell wall damaging conditions, which results in the differential regulation of >100 genes. While the effectors of VxrAB are relatively well known, VxrAB environment-sensing and activation mechanisms remain a mystery. Here, we used transposon mutagenesis to screen for mutants that spontaneously upregulate VxrAB signaling. This screen was answered by genes known to be required for proper cell envelope homeostasis, validating the approach. Unexpectedly, we also uncovered a new connection between central carbon metabolism and antibiotic tolerance in Vibrio cholerae. Inactivation of
    MeSH term(s) Vibrio cholerae/metabolism ; Mutation ; Penicillins/pharmacology ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/metabolism ; Monobactams/metabolism ; beta-Lactams/pharmacology
    Chemical Substances Penicillins ; Anti-Bacterial Agents ; Monobactams ; beta-Lactams
    Language English
    Publishing date 2023-02-22
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 2968-3
    ISSN 1098-5530 ; 0021-9193
    ISSN (online) 1098-5530
    ISSN 0021-9193
    DOI 10.1128/jb.00476-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Multiple resistance factors collectively promote inoculum-dependent dynamic survival during antimicrobial peptide exposure in

    Murtha, Andrew N / Kazi, Misha / Kim, Eileen / Rosch, Kelly M / Torres, Facundo / Dörr, Tobias

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Antimicrobial peptides (AMPs) are a promising tool with which to fight rising antibiotic resistance. However, pathogenic bacteria are equipped with several AMP defense mechanisms, whose contributions to AMP resistance are often poorly defined. Here, we ... ...

    Abstract Antimicrobial peptides (AMPs) are a promising tool with which to fight rising antibiotic resistance. However, pathogenic bacteria are equipped with several AMP defense mechanisms, whose contributions to AMP resistance are often poorly defined. Here, we evaluate the genetic determinants of resistance to an insect AMP, cecropin B, in the opportunistic pathogen
    Language English
    Publishing date 2024-03-03
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.03.583169
    Database MEDical Literature Analysis and Retrieval System OnLINE

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