The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform

Luisa Kielty - One of the best experts on this subject based on the ideXlab platform.

  • Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials.
    Nature microbiology, 2021
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    We characterized two bacteriophages, ΦFG02 and ΦCO01, against clinical isolates of Acinetobacter baumannii and established that the Bacterial Capsule is the receptor for these phages. Phage-resistant mutants harboured loss-of-function mutations in genes responsible for Capsule biosynthesis, resulting in Capsule loss and disruption of phage adsorption. The phage-resistant strains were resensitized to human complement, beta-lactam antibiotics and alternative phages and exhibited diminished fitness in vivo. Using a mouse model of A. baumannii infection, we showed that phage therapy was effective.

  • Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials
    Nature Microbiology, 2021
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    We characterized two bacteriophages, ΦFG02 and ΦCO01, against clinical isolates of Acinetobacter baumannii and established that the Bacterial Capsule is the receptor for these phages. Phage-resistant mutants harboured loss-of-function mutations in genes responsible for Capsule biosynthesis, resulting in Capsule loss and disruption of phage adsorption. The phage-resistant strains were resensitized to human complement, beta-lactam antibiotics and alternative phages and exhibited diminished fitness in vivo. Using a mouse model of A. baumannii infection, we showed that phage therapy was effective. The authors characterize two phages against Acinetobacter baumannii , both in vitro and in vivo. A. baumannii strains develop resistance against both phages, but are in turn resensitized to different antimicrobial compounds.

  • Bacteriophages targeting Acinetobacter baumannii Capsule induce antimicrobial resensitization
    2020
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    Carbapenem-resistant Acinetobacter baumannii is responsible for frequent, hard-to-treat and often fatal healthcare-associated infections. Phage therapy, the use of viruses that infect and kill bacteria, is an approach gaining significant clinical interest to combat antibiotic-resistant infections. However, a major limitation is that bacteria can develop resistance against phages. Here, we isolated phages with activity against a panel of A. baumannii strains and focused on clinical isolates AB900 and A9844 and their phages for detailed characterization. As expected, coincubation of the phages with their hosts in vitro resulted in the emergence of phage-resistant Bacterial mutants. Genome sequence analysis revealed that phage-resistant mutants harbored loss-of-function mutations in genes from the K locus, responsible for the biosynthesis of the Bacterial Capsule. Using molecular biology techniques, phage adsorption assays, and quantitative evaluation of Capsule production, we established that the Bacterial Capsule serves as the primary receptor for these phages. As a collateral phenotype of impaired Capsule production, the phage-resistant strains could not form biofilms, became fully sensitized to the human complement system, showed increased susceptibility to beta-lactam antibiotics, and became vulnerable to additional phages. Finally, in a murine model of bacteremia, the phage-resistant A. baumannii demonstrated a diminished capacity to colonize blood and solid tissues. This study demonstrates that phages can be used not only for their lytic activity but, if combined with a posteriori knowledge of their receptors and the mechanism of Bacterial resistance, for their potential synergy with other antimicrobial agents, thus providing even broader clinical options for phage therapy.

Sarkis K Mazmanian - One of the best experts on this subject based on the ideXlab platform.

  • regulation of surface architecture by symbiotic bacteria mediates host colonization
    Proceedings of the National Academy of Sciences of the United States of America, 2008
    Co-Authors: Jordan M Vanlare, Sarkis K Mazmanian, Dennis L. Kasper
    Abstract:

    Microbes occupy countless ecological niches in nature. Sometimes these environments may be on or within another organism, as is the case in both microbial infections and symbiosis of mammals. Unlike pathogens that establish opportunistic infections, hundreds of human commensal Bacterial species establish a lifelong cohabitation with their hosts. Although many virulence factors of infectious bacteria have been described, the molecular mechanisms used during beneficial host–symbiont colonization remain almost entirely unknown. The novel identification of multiple surface polysaccharides in the important human symbiont Bacteroides fragilis raised the critical question of how these molecules contribute to commensalism. To understand the function of the Bacterial Capsule during symbiotic colonization of mammals, we generated B. fragilis strains deleted in the global regulator of polysaccharide expression and isolated mutants with defects in Capsule expression. Surprisingly, attempts to completely eliminate Capsule production are not tolerated by the microorganism, which displays growth deficits and subsequent reversion to express capsular polysaccharides. We identify an alternative pathway by which B. fragilis is able to reestablish Capsule production and modulate expression of surface structures. Most importantly, mutants expressing single, defined surface polysaccharides are defective for intestinal colonization compared with bacteria expressing a complete polysaccharide repertoire. Restoring the expression of multiple capsular polysaccharides rescues the inability of mutants to compete for commensalism. These findings suggest a model whereby display of multiple capsular polysaccharides provides essential functions for Bacterial colonization during host–symbiont mutualism.

Dinesh Subedi - One of the best experts on this subject based on the ideXlab platform.

  • Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials.
    Nature microbiology, 2021
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    We characterized two bacteriophages, ΦFG02 and ΦCO01, against clinical isolates of Acinetobacter baumannii and established that the Bacterial Capsule is the receptor for these phages. Phage-resistant mutants harboured loss-of-function mutations in genes responsible for Capsule biosynthesis, resulting in Capsule loss and disruption of phage adsorption. The phage-resistant strains were resensitized to human complement, beta-lactam antibiotics and alternative phages and exhibited diminished fitness in vivo. Using a mouse model of A. baumannii infection, we showed that phage therapy was effective.

  • Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials
    Nature Microbiology, 2021
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    We characterized two bacteriophages, ΦFG02 and ΦCO01, against clinical isolates of Acinetobacter baumannii and established that the Bacterial Capsule is the receptor for these phages. Phage-resistant mutants harboured loss-of-function mutations in genes responsible for Capsule biosynthesis, resulting in Capsule loss and disruption of phage adsorption. The phage-resistant strains were resensitized to human complement, beta-lactam antibiotics and alternative phages and exhibited diminished fitness in vivo. Using a mouse model of A. baumannii infection, we showed that phage therapy was effective. The authors characterize two phages against Acinetobacter baumannii , both in vitro and in vivo. A. baumannii strains develop resistance against both phages, but are in turn resensitized to different antimicrobial compounds.

  • Bacteriophages targeting Acinetobacter baumannii Capsule induce antimicrobial resensitization
    2020
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    Carbapenem-resistant Acinetobacter baumannii is responsible for frequent, hard-to-treat and often fatal healthcare-associated infections. Phage therapy, the use of viruses that infect and kill bacteria, is an approach gaining significant clinical interest to combat antibiotic-resistant infections. However, a major limitation is that bacteria can develop resistance against phages. Here, we isolated phages with activity against a panel of A. baumannii strains and focused on clinical isolates AB900 and A9844 and their phages for detailed characterization. As expected, coincubation of the phages with their hosts in vitro resulted in the emergence of phage-resistant Bacterial mutants. Genome sequence analysis revealed that phage-resistant mutants harbored loss-of-function mutations in genes from the K locus, responsible for the biosynthesis of the Bacterial Capsule. Using molecular biology techniques, phage adsorption assays, and quantitative evaluation of Capsule production, we established that the Bacterial Capsule serves as the primary receptor for these phages. As a collateral phenotype of impaired Capsule production, the phage-resistant strains could not form biofilms, became fully sensitized to the human complement system, showed increased susceptibility to beta-lactam antibiotics, and became vulnerable to additional phages. Finally, in a murine model of bacteremia, the phage-resistant A. baumannii demonstrated a diminished capacity to colonize blood and solid tissues. This study demonstrates that phages can be used not only for their lytic activity but, if combined with a posteriori knowledge of their receptors and the mechanism of Bacterial resistance, for their potential synergy with other antimicrobial agents, thus providing even broader clinical options for phage therapy.

Cody Oliveira - One of the best experts on this subject based on the ideXlab platform.

  • Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials.
    Nature microbiology, 2021
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    We characterized two bacteriophages, ΦFG02 and ΦCO01, against clinical isolates of Acinetobacter baumannii and established that the Bacterial Capsule is the receptor for these phages. Phage-resistant mutants harboured loss-of-function mutations in genes responsible for Capsule biosynthesis, resulting in Capsule loss and disruption of phage adsorption. The phage-resistant strains were resensitized to human complement, beta-lactam antibiotics and alternative phages and exhibited diminished fitness in vivo. Using a mouse model of A. baumannii infection, we showed that phage therapy was effective.

  • Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials
    Nature Microbiology, 2021
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    We characterized two bacteriophages, ΦFG02 and ΦCO01, against clinical isolates of Acinetobacter baumannii and established that the Bacterial Capsule is the receptor for these phages. Phage-resistant mutants harboured loss-of-function mutations in genes responsible for Capsule biosynthesis, resulting in Capsule loss and disruption of phage adsorption. The phage-resistant strains were resensitized to human complement, beta-lactam antibiotics and alternative phages and exhibited diminished fitness in vivo. Using a mouse model of A. baumannii infection, we showed that phage therapy was effective. The authors characterize two phages against Acinetobacter baumannii , both in vitro and in vivo. A. baumannii strains develop resistance against both phages, but are in turn resensitized to different antimicrobial compounds.

  • Bacteriophages targeting Acinetobacter baumannii Capsule induce antimicrobial resensitization
    2020
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    Carbapenem-resistant Acinetobacter baumannii is responsible for frequent, hard-to-treat and often fatal healthcare-associated infections. Phage therapy, the use of viruses that infect and kill bacteria, is an approach gaining significant clinical interest to combat antibiotic-resistant infections. However, a major limitation is that bacteria can develop resistance against phages. Here, we isolated phages with activity against a panel of A. baumannii strains and focused on clinical isolates AB900 and A9844 and their phages for detailed characterization. As expected, coincubation of the phages with their hosts in vitro resulted in the emergence of phage-resistant Bacterial mutants. Genome sequence analysis revealed that phage-resistant mutants harbored loss-of-function mutations in genes from the K locus, responsible for the biosynthesis of the Bacterial Capsule. Using molecular biology techniques, phage adsorption assays, and quantitative evaluation of Capsule production, we established that the Bacterial Capsule serves as the primary receptor for these phages. As a collateral phenotype of impaired Capsule production, the phage-resistant strains could not form biofilms, became fully sensitized to the human complement system, showed increased susceptibility to beta-lactam antibiotics, and became vulnerable to additional phages. Finally, in a murine model of bacteremia, the phage-resistant A. baumannii demonstrated a diminished capacity to colonize blood and solid tissues. This study demonstrates that phages can be used not only for their lytic activity but, if combined with a posteriori knowledge of their receptors and the mechanism of Bacterial resistance, for their potential synergy with other antimicrobial agents, thus providing even broader clinical options for phage therapy.

Faye C. Morris - One of the best experts on this subject based on the ideXlab platform.

  • Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials.
    Nature microbiology, 2021
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    We characterized two bacteriophages, ΦFG02 and ΦCO01, against clinical isolates of Acinetobacter baumannii and established that the Bacterial Capsule is the receptor for these phages. Phage-resistant mutants harboured loss-of-function mutations in genes responsible for Capsule biosynthesis, resulting in Capsule loss and disruption of phage adsorption. The phage-resistant strains were resensitized to human complement, beta-lactam antibiotics and alternative phages and exhibited diminished fitness in vivo. Using a mouse model of A. baumannii infection, we showed that phage therapy was effective.

  • Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials
    Nature Microbiology, 2021
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    We characterized two bacteriophages, ΦFG02 and ΦCO01, against clinical isolates of Acinetobacter baumannii and established that the Bacterial Capsule is the receptor for these phages. Phage-resistant mutants harboured loss-of-function mutations in genes responsible for Capsule biosynthesis, resulting in Capsule loss and disruption of phage adsorption. The phage-resistant strains were resensitized to human complement, beta-lactam antibiotics and alternative phages and exhibited diminished fitness in vivo. Using a mouse model of A. baumannii infection, we showed that phage therapy was effective. The authors characterize two phages against Acinetobacter baumannii , both in vitro and in vivo. A. baumannii strains develop resistance against both phages, but are in turn resensitized to different antimicrobial compounds.

  • Bacteriophages targeting Acinetobacter baumannii Capsule induce antimicrobial resensitization
    2020
    Co-Authors: Fernando Gordillo Altamirano, John H. Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K. Archer, Faye C. Morris, Cody Oliveira, Luisa Kielty
    Abstract:

    Carbapenem-resistant Acinetobacter baumannii is responsible for frequent, hard-to-treat and often fatal healthcare-associated infections. Phage therapy, the use of viruses that infect and kill bacteria, is an approach gaining significant clinical interest to combat antibiotic-resistant infections. However, a major limitation is that bacteria can develop resistance against phages. Here, we isolated phages with activity against a panel of A. baumannii strains and focused on clinical isolates AB900 and A9844 and their phages for detailed characterization. As expected, coincubation of the phages with their hosts in vitro resulted in the emergence of phage-resistant Bacterial mutants. Genome sequence analysis revealed that phage-resistant mutants harbored loss-of-function mutations in genes from the K locus, responsible for the biosynthesis of the Bacterial Capsule. Using molecular biology techniques, phage adsorption assays, and quantitative evaluation of Capsule production, we established that the Bacterial Capsule serves as the primary receptor for these phages. As a collateral phenotype of impaired Capsule production, the phage-resistant strains could not form biofilms, became fully sensitized to the human complement system, showed increased susceptibility to beta-lactam antibiotics, and became vulnerable to additional phages. Finally, in a murine model of bacteremia, the phage-resistant A. baumannii demonstrated a diminished capacity to colonize blood and solid tissues. This study demonstrates that phages can be used not only for their lytic activity but, if combined with a posteriori knowledge of their receptors and the mechanism of Bacterial resistance, for their potential synergy with other antimicrobial agents, thus providing even broader clinical options for phage therapy.