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  1. Article ; Online: Bacterial conversion of a host weapon into a nutritional signal.

    Valvano, Miguel A

    The Journal of biological chemistry

    2022  Volume 298, Issue 11, Page(s) 102600

    Abstract: Bacteria engulfed by phagocytic cells must resist oxidation damage and adapt to cellular hypoxia, but the mechanisms involved in this process are not completely elucidated. Recent work by Kim et al. in the Journal of Biological Chemistry investigated how ...

    Abstract Bacteria engulfed by phagocytic cells must resist oxidation damage and adapt to cellular hypoxia, but the mechanisms involved in this process are not completely elucidated. Recent work by Kim et al. in the Journal of Biological Chemistry investigated how the intracellular pathogen Salmonella enterica activates gene expression required to counteract oxidative damage. The authors show that this bacterium utilizes host oxidative molecules to activate regulatory proteins that enhance the production of effector molecules, counteracting the host weapon NADPH oxidase and inducing a protective response.
    MeSH term(s) NADPH Oxidases/metabolism ; Salmonella enterica/genetics ; Oxidative Stress ; Oxidation-Reduction ; Phagocytes/metabolism ; Bacterial Proteins/metabolism
    Chemical Substances NADPH Oxidases (EC 1.6.3.-) ; Bacterial Proteins
    Language English
    Publishing date 2022-10-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2022.102600
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  2. Article ; Online: Remodelling of the Gram-negative bacterial Kdo

    Valvano, Miguel A

    Microbiology (Reading, England)

    2022  Volume 168, Issue 4

    Abstract: The lipopolysaccharide (LPS) is a characteristic molecule of the outer leaflet of the Gram-negative bacterial outer membrane, which consists of lipid A, core oligosaccharide, and O antigen. The lipid A is embedded in outer membrane and provides an ... ...

    Abstract The lipopolysaccharide (LPS) is a characteristic molecule of the outer leaflet of the Gram-negative bacterial outer membrane, which consists of lipid A, core oligosaccharide, and O antigen. The lipid A is embedded in outer membrane and provides an efficient permeability barrier, which is particularly important to reduce the permeability of antibiotics, toxic cationic metals, and antimicrobial peptides. LPS, an important modulator of innate immune responses ranging from localized inflammation to disseminated sepsis, displays a high level of structural and functional heterogeneity, which arise due to regulated differences in the acylation of the lipid A and the incorporation of non-stoichiometric modifications in lipid A and the core oligosaccharide. This review focuses on the current mechanistic understanding of the synthesis and assembly of the lipid A molecule and its most salient non-stoichiometric modifications.
    MeSH term(s) Bacterial Outer Membrane ; Bacterial Outer Membrane Proteins/metabolism ; Gram-Negative Bacteria/genetics ; Gram-Negative Bacteria/metabolism ; Lipid A/chemistry ; Lipid A/metabolism ; Lipopolysaccharides/chemistry
    Chemical Substances Bacterial Outer Membrane Proteins ; Lipid A ; Lipopolysaccharides
    Language English
    Publishing date 2022-04-08
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180712-x
    ISSN 1465-2080 ; 1350-0872
    ISSN (online) 1465-2080
    ISSN 1350-0872
    DOI 10.1099/mic.0.001159
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  3. Article ; Online: BCG to Protect against Covid-19 in Health Care Workers.

    Lopez-Campos, Guillermo H / Valvano, Miguel A

    The New England journal of medicine

    2023  Volume 389, Issue 2, Page(s) 191

    MeSH term(s) Humans ; BCG Vaccine ; COVID-19/prevention & control ; Health Personnel
    Chemical Substances BCG Vaccine
    Language English
    Publishing date 2023-07-12
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc2306483
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  4. Article ; Online: Exploring the Topology of Cytoplasmic Membrane Proteins Involved in Lipopolysaccharide Biosynthesis by in Silico and Biochemical Analyses.

    Monjarás Feria, Julia / Valvano, Miguel A

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2548, Page(s) 71–82

    Abstract: In the absence of a tri-dimensional structure, revealing the topology of a membrane protein provides relevant information to identify the number and orientation of transmembrane helices and the localization of critical amino acid residues, contributing ... ...

    Abstract In the absence of a tri-dimensional structure, revealing the topology of a membrane protein provides relevant information to identify the number and orientation of transmembrane helices and the localization of critical amino acid residues, contributing to a better understanding of function and intermolecular associations. Topology can be predicted in silico by bioinformatic analysis or solved by biochemical methods. In this chapter, we describe a pipeline employing bioinformatic approaches for the prediction of membrane protein topology, followed by experimental validation through the substituted-cysteine accessibility method and the analysis of the protein's oligomerization state.
    MeSH term(s) Amino Acids/metabolism ; Cell Membrane/metabolism ; Cysteine/chemistry ; Lipopolysaccharides/metabolism ; Membrane Proteins/metabolism
    Chemical Substances Amino Acids ; Lipopolysaccharides ; Membrane Proteins ; Cysteine (K848JZ4886)
    Language English
    Publishing date 2022-09-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2581-1_5
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  5. Article ; Online: Distribution and diversity of type VI secretion system clusters in

    Anderson, Amy J G / Morrell, Becca / Lopez Campos, Guillermo / Valvano, Miguel A

    Microbial genomics

    2023  Volume 9, Issue 12

    Abstract: Gram-negative bacteria use type VI secretion systems (T6SSs) to antagonize neighbouring cells. Although primarily involved in bacterial competition, the T6SS is also implicated in pathogenesis, biofilm formation and ion scavenging. ...

    Abstract Gram-negative bacteria use type VI secretion systems (T6SSs) to antagonize neighbouring cells. Although primarily involved in bacterial competition, the T6SS is also implicated in pathogenesis, biofilm formation and ion scavenging.
    MeSH term(s) Enterobacter cloacae/genetics ; Type VI Secretion Systems/genetics ; Peptide Hydrolases
    Chemical Substances Type VI Secretion Systems ; Peptide Hydrolases (EC 3.4.-)
    Language English
    Publishing date 2023-12-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835258-0
    ISSN 2057-5858 ; 2057-5858
    ISSN (online) 2057-5858
    ISSN 2057-5858
    DOI 10.1099/mgen.0.001148
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  6. Article ; Online: Phage treatment of Pseudomonas aeruginosa yields a phage-resistant population with different susceptibility to innate immune responses and mild effects on metabolic profiles.

    Olszak, Tomasz / Augustyniak, Daria / García-Romero, Inmaculada / Markwitz, Pawel / Gula, Grzegorz / Molinaro, Antonio / Valvano, Miguel A / Drulis-Kawa, Zuzanna

    Microbiological research

    2024  Volume 282, Page(s) 127609

    Abstract: In this study, we have investigated innate immune activation capacity and metabolic features of a population of P. aeruginosa PAO1 phage-resistant mutants with diverse genetic modification (large genomic deletions and point mutations) arising after ... ...

    Abstract In this study, we have investigated innate immune activation capacity and metabolic features of a population of P. aeruginosa PAO1 phage-resistant mutants with diverse genetic modification (large genomic deletions and point mutations) arising after exposure to phages targetting lipopolysaccharide (LPS) or Type-4 pili (T4P). Deletions led to the loss of genes involved in LPS synthesis, cell envelope permeability, efflux systems, biofilm production, oxidative stress tolerance, and DNA repair. Loss of LPS O antigen resulted in bacterial sensitivity to serum complement and stimulation of inflammatory cascades but did not cause increased phagocytosis, while T4P phage-resistant mutants were more effectively phagocytized than LPS-defective mutants. Changes in the utilization of different carbon, nitrogen, sulphur, and phosphorus sources were identified, especially in mutants where the two phage DNA persisted in the bacterial population (pseudolysogeny). However, the metabolic changes did not directly correlate with single-gene mutations or the large gene deletions, suggesting they reflect adaptive changes to the gene modifications that arise during the selection of resistant mutants. In contrast, phage-resistant mutants were susceptible to humoral innate immune responses, suggesting that phage resistance may be a beneficial outcome of phage therapy.
    MeSH term(s) Bacteriophages ; Pseudomonas aeruginosa/metabolism ; Lipopolysaccharides ; Bacteria/metabolism ; Immunity, Innate ; Metabolome
    Chemical Substances Lipopolysaccharides
    Language English
    Publishing date 2024-01-12
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1189614-0
    ISSN 1618-0623 ; 0944-5013
    ISSN (online) 1618-0623
    ISSN 0944-5013
    DOI 10.1016/j.micres.2024.127609
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  7. Article ; Online: Drug efflux and lipid A modification by 4-L-aminoarabinose are key mechanisms of polymyxin B resistance in the sepsis pathogen Enterobacter bugandensis.

    García-Romero, Inmaculada / Srivastava, Mugdha / Monjarás-Feria, Julia / Korankye, Samuel O / MacDonald, Lewis / Scott, Nichollas E / Valvano, Miguel A

    Journal of global antimicrobial resistance

    2024  Volume 37, Page(s) 108–121

    Abstract: Objectives: A concern with the ESKAPE pathogen, Enterobacter bugandensis, and other species of the Enterobacter cloacae complex, is the frequent appearance of multidrug resistance against last-resort antibiotics, such as polymyxins.: Methods: Here, ... ...

    Abstract Objectives: A concern with the ESKAPE pathogen, Enterobacter bugandensis, and other species of the Enterobacter cloacae complex, is the frequent appearance of multidrug resistance against last-resort antibiotics, such as polymyxins.
    Methods: Here, we investigated the responses to polymyxin B (PMB) in two PMB-resistant E. bugandensis clinical isolates by global transcriptomics and deletion mutagenesis.
    Results: In both isolates, the genes of the CrrAB-regulated operon, including crrC and kexD, displayed the highest levels of upregulation in response to PMB. ∆crrC and ∆kexD mutants became highly susceptible to PMB and lost the heteroresistant phenotype. Conversely, heterologous expression of CrrC and KexD proteins increased PMB resistance in a sensitive Enterobacter ludwigii clinical isolate and in the Escherichia coli K12 strain, W3110. The efflux pump, AcrABTolC, and the two component regulators, PhoPQ and CrrAB, also contributed to PMB resistance and heteroresistance. Additionally, the lipid A modification with 4-L-aminoarabinose (L-Ara4N), mediated by the arnBCADTEF operon, was critical to determine PMB resistance. Biochemical experiments, supported by mass spectrometry and structural modelling, indicated that CrrC is an inner membrane protein that interacts with the membrane domain of the KexD pump. Similar interactions were modeled for AcrB and AcrD efflux pumps.
    Conclusion: Our results support a model where drug efflux potentiated by CrrC interaction with membrane domains of major efflux pumps combined with resistance to PMB entry by the L-Ara4N lipid A modification, under the control of PhoPQ and CrrAB, confers the bacterium high-level resistance and heteroresistance to PMB.
    Language English
    Publishing date 2024-03-27
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2710046-7
    ISSN 2213-7173 ; 2213-7173
    ISSN (online) 2213-7173
    ISSN 2213-7173
    DOI 10.1016/j.jgar.2024.03.012
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  8. Article: Comparative analysis of

    Adade, Nana Eghele / Aniweh, Yaw / Mosi, Lydia / Valvano, Miguel A / Duodu, Samuel / Ahator, Stephen Dela

    Frontiers in microbiology

    2022  Volume 13, Page(s) 998182

    Abstract: Recurrent epidemics of cholera denote robust adaptive mechanisms ... ...

    Abstract Recurrent epidemics of cholera denote robust adaptive mechanisms of
    Language English
    Publishing date 2022-10-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2022.998182
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  9. Article ; Online: Intracellular survival of Burkholderia cepacia complex in phagocytic cells.

    Valvano, Miguel A

    Canadian journal of microbiology

    2015  Volume 61, Issue 9, Page(s) 607–615

    Abstract: Burkholderia cepacia complex (Bcc) species are a group of Gram-negative opportunistic pathogens that infect the airways of cystic fibrosis patients, and occasionally they infect other immunocompromised patients. Bcc bacteria display high-level multidrug ... ...

    Abstract Burkholderia cepacia complex (Bcc) species are a group of Gram-negative opportunistic pathogens that infect the airways of cystic fibrosis patients, and occasionally they infect other immunocompromised patients. Bcc bacteria display high-level multidrug resistance and chronically persist in the infected host while eliciting robust inflammatory responses. Studies using macrophages, neutrophils, and dendritic cells, combined with advances in the genetic manipulation of these bacteria, have increased our understanding of the molecular mechanisms of virulence in these pathogens and the molecular details of cell-host responses triggering inflammation. This article discusses our current view of the intracellular survival of Burkholderia cenocepacia within macrophages.
    MeSH term(s) Burkholderia Infections/immunology ; Burkholderia Infections/microbiology ; Burkholderia cepacia complex/genetics ; Burkholderia cepacia complex/growth & development ; Burkholderia cepacia complex/metabolism ; Cytokines/immunology ; Humans ; Macrophages/immunology ; Macrophages/microbiology ; Microbial Viability ; Neutrophils/immunology ; Neutrophils/microbiology ; Virulence
    Chemical Substances Cytokines
    Language English
    Publishing date 2015-09
    Publishing country Canada
    Document type Journal Article
    ZDB-ID 280534-0
    ISSN 1480-3275 ; 0008-4166
    ISSN (online) 1480-3275
    ISSN 0008-4166
    DOI 10.1139/cjm-2015-0316
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  10. Article ; Online: Complete Genome Sequence of Burkholderia cenocepacia K56-2, an Opportunistic Pathogen.

    García-Romero, Inmaculada / Valvano, Miguel A

    Microbiology resource announcements

    2020  Volume 9, Issue 43

    Abstract: Burkholderia ... ...

    Abstract Burkholderia cenocepacia
    Language English
    Publishing date 2020-10-22
    Publishing country United States
    Document type Journal Article
    ISSN 2576-098X
    ISSN (online) 2576-098X
    DOI 10.1128/MRA.01015-20
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