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  • 1
    In: mBio, American Society for Microbiology, Vol. 10, No. 3 ( 2019-06-25)
    Kurzfassung: Host-to-host transmission is a necessary but poorly understood aspect of microbial pathogenesis. Herein, we screened a genomic library of mutants of the leading respiratory pathogen Streptococcus pneumoniae generated by mariner transposon mutagenesis (Tn-Seq) to identify genes contributing to its exit or shedding from the upper respiratory tract (URT), the limiting step in the organism’s transmission in an infant mouse model. Our analysis focused on genes affecting the bacterial surface that directly impact interactions with the host. Among the multiple factors identified was the dlt locus, which adds d -alanine onto lipoteichoic acids (LTA) and thereby increases Toll-like receptor 2-mediated inflammation and resistance to antimicrobial peptides. The more robust proinflammatory response in the presence of d -alanylation promotes secretions that facilitate pneumococcal shedding and allows for transmission. Expression of the dlt locus is controlled by the CiaRH system, which senses cell wall stress in response to antimicrobial activity, including in response to lysozyme, the most abundant antimicrobial along the URT mucosa. Accordingly, in a lysM −/− host, there was no longer an effect of the dlt locus on pneumococcal shedding. Thus, our findings demonstrate how a pathogen senses the URT milieu and then modifies its surface characteristics to take advantage of the host response for transit to another host. IMPORTANCE Streptococcus pneumoniae (the pneumococcus) is a common cause of respiratory tract and invasive infection. The overall effectiveness of immunization with the organism’s capsular polysaccharide depends on its ability to block colonization of the upper respiratory tract and thereby prevent host-to-host transmission. Because of the limited coverage of current pneumococcal vaccines, we carried out an unbiased in vivo transposon mutagenesis screen to identify pneumococcal factors other than its capsular polysaccharide that affect transmission. One such candidate was expressed by the dlt locus, previously shown to add d -alanine onto the pneumococcal lipoteichoic acid present on the bacterial cell surface. This modification protects against host antimicrobials and augments host inflammatory responses. The latter increases secretions and bacterial shedding from the upper respiratory tract to allow for transmission. Thus, this study provides insight into a mechanism employed by the pneumococcus to successfully transit from one host to another.
    Materialart: Online-Ressource
    ISSN: 2161-2129 , 2150-7511
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2019
    ZDB Id: 2557172-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    American Society for Microbiology ; 2019
    In:  mBio Vol. 10, No. 3 ( 2019-06-25)
    In: mBio, American Society for Microbiology, Vol. 10, No. 3 ( 2019-06-25)
    Kurzfassung: Temperate phages encode an immunity system to control lytic gene expression during lysogeny. This gene regulatory circuit consists of multiple interacting genetic elements, and although it is essential for controlling phage growth, it is subject to conflicting evolutionary pressures. During superinfection of a lysogen, the prophage’s circuit interacts with the superinfecting phage’s circuit and prevents lytic growth if the two circuits are closely related. The circuitry is advantageous since it provides the prophage with a defense mechanism, but the circuitry is also disadvantageous since it limits the phage’s host range during superinfection. Evolutionarily related phages have divergent, orthogonal immunity systems that no longer interact and are heteroimmune, but we do not understand how immunity systems evolve new specificities. Here, we use a group of Cluster A mycobacteriophages that exhibit a spectrum of genetic diversity to examine how immunity system evolution impacts superinfection immunity. We show that phages with mesotypic (i.e., genetically related but distinct) immunity systems exhibit asymmetric and incomplete superinfection phenotypes. They form complex immunity networks instead of well-defined immunity groups, and mutations conferring escape (i.e., virulence) from homotypic or mesotypic immunity have various escape specificities. Thus, virulence and the evolution of new immune specificities are shaped by interactions with homotypic and mesotypic immunity systems. IMPORTANCE Many aspects regarding superinfection, immunity, virulence, and the evolution of immune specificities are poorly understood due to the lack of large collections of isolated and sequenced phages with a spectrum of genetic diversity. Using a genetically diverse collection of Cluster A phages, we show that the classical and relatively straightforward patterns of homoimmunity, heteroimmunity, and virulence result from interactions between homotypic and heterotypic phages at the extreme edges of an evolutionary continuum of immune specificities. Genetic interactions between mesotypic phages result in more complex mesoimmunity phenotypes and virulence profiles. These results highlight that the evolution of immune specificities can be shaped by homotypic and mesotypic interactions and may be more dynamic than previously considered.
    Materialart: Online-Ressource
    ISSN: 2161-2129 , 2150-7511
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2019
    ZDB Id: 2557172-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Online-Ressource
    Online-Ressource
    Springer Science and Business Media LLC ; 2008
    In:  Genome Biology Vol. 9, No. 6 ( 2008), p. 225-
    In: Genome Biology, Springer Science and Business Media LLC, Vol. 9, No. 6 ( 2008), p. 225-
    Materialart: Online-Ressource
    ISSN: 1465-6906
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2008
    ZDB Id: 2040529-7
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Genome Biology, Springer Science and Business Media LLC, Vol. 11, No. 10 ( 2010-10)
    Materialart: Online-Ressource
    ISSN: 1474-760X
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2010
    ZDB Id: 2040529-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Current Opinion in Otolaryngology & Head & Neck Surgery Vol. 15, No. 5 ( 2007-10), p. 347-351
    In: Current Opinion in Otolaryngology & Head & Neck Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 15, No. 5 ( 2007-10), p. 347-351
    Materialart: Online-Ressource
    ISSN: 1068-9508
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2007
    ZDB Id: 2026964-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2018
    In:  Frontiers in Microbiology Vol. 9 ( 2018-10-30)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 9 ( 2018-10-30)
    Materialart: Online-Ressource
    ISSN: 1664-302X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2018
    ZDB Id: 2587354-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    American Society for Microbiology ; 2021
    In:  mBio Vol. 12, No. 3 ( 2021-06-29)
    In: mBio, American Society for Microbiology, Vol. 12, No. 3 ( 2021-06-29)
    Kurzfassung: Regulation of flagellum biosynthesis is a hierarchical process that is tightly controlled to allow for efficient tuning of flagellar expression. Flagellum-mediated motility directs Salmonella enterica serovar Typhimurium toward the epithelial surface to enhance gut colonization, but flagella are potent activators of innate immune signaling, so fine-tuning flagellar expression is necessary for immune avoidance. In this work, we evaluate the role of the LysR transcriptional regulator YeiE in regulating flagellum-mediated motility. We show that yeiE is necessary and sufficient for swimming motility. A ΔyeiE mutant is defective for gut colonization in both the calf ligated ileal loop model and the murine colitis model due to its lack of motility. Expression of flagellar class 2 and 3 but not class 1 genes is reduced in the Δ yeiE mutant. We linked the motility dysregulation of the Δ yeiE mutant to repression of the anti-FlhD 4 C 2 factor STM1697. Together, our results indicate that YeiE promotes virulence by enhancing cell motility, thereby providing a new regulatory control point for flagellar expression in Salmonella Typhimurium. IMPORTANCE The ability to finely tune virulence factor gene expression is required for bacterial pathogens to successfully colonize a host. Flagellum-mediated motility is critical for many gut pathogens to establish productive infections. However, flagella activate the immune system, leading to bacterial clearance; therefore, tight control of flagellar gene expression enhances bacterial fitness in the host. Here, we demonstrate that the transcriptional regulator YeiE acts as a control point for flagellar gene expression and is required for Salmonella Typhimurium to establish a productive infection in mammals. The expression of an inhibitor of flagellar biogenesis is repressed in the absence of yeiE . Our work adds a new layer to the tightly controlled cascade regulating control of flagellar gene expression to facilitate the fitness of an enteric pathogen.
    Materialart: Online-Ressource
    ISSN: 2150-7511
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2021
    ZDB Id: 2557172-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: mBio, American Society for Microbiology, Vol. 10, No. 2 ( 2019-04-30)
    Kurzfassung: Temperate phages play important roles in the physiology of their bacterial hosts and establish a lysogenic relationship with the host through which prophage-expressed genes confer new phenotypes. A key phenotype is prophage-mediated defense against heterotypic viral attack, in which temperate phages collude with their bacterial host to prevent other phages from attacking, sometimes with exquisite specificity. Such defense systems have been described in Pseudomonas and Mycobacterium phages but are likely widespread throughout the microbial community. Here, we describe a novel prophage-mediated defense system encoded by Gordonia phage CarolAnn, which defends against infection by unrelated phages grouped in cluster CZ. CarolAnn genes 43 and 44 are coexpressed with the repressor and are necessary and sufficient to confer defense against phage Kita and its close relatives. Kita and these relatives are targeted through Kita gene 53 , a gene that is of unknown function but which is the location of defense escape mutations that overcome CarolAnn defense. Expression of Kita gene 53 is toxic to Gordonia terrae in the presence of CarolAnn genes 43 and 44 , suggesting that defense may be mediated by an abortive infection type of mechanism. CarolAnn genes 43 and 44 are distant relatives of mycobacteriophage Sbash genes 31 and 30 , respectively, which also confer viral defense but use a different targeting system. IMPORTANCE Prophage-mediated viral defense systems play a key role in microbial dynamics, as lysogeny is established relatively efficiently, and prophage-expressed genes can strongly inhibit lytic infection of other, unrelated phages. Demonstrating such defense systems in Gordonia terrae suggests that these systems are widespread and that there are a multitude of different systems with different specificities for the attacking phages.
    Materialart: Online-Ressource
    ISSN: 2161-2129 , 2150-7511
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2019
    ZDB Id: 2557172-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: mBio, American Society for Microbiology, Vol. 13, No. 2 ( 2022-04-26)
    Kurzfassung: Carbapenem-resistant Acinetobacter baumannii (CR Ab ) is a major cause of health care-associated infections. CR Ab is typically multidrug resistant, and infection is difficult to treat. Despite the urgent threat that CR Ab poses, few systematic studies of CR Ab clinical and molecular epidemiology have been conducted. The Study Network of Acinetobacter as a Carbapenem-Resistant Pathogen (SNAP) is designed to investigate the clinical characteristics and contemporary population structure of CR Ab circulating in U.S. hospital systems using whole-genome sequencing (WGS). Analysis of the initial 120 SNAP patients from four U.S. centers revealed that CR Ab remains a significant threat to hospitalized patients, affecting the most vulnerable patients and resulting in 24% all-cause 30-day mortality. The majority of currently circulating isolates belonged to ST2 Pas , a part of clonal complex 2 (CC2), which is the dominant drug-resistant lineage in the United States and Europe. We identified three distinct sublineages within CC2, which differed in their antibiotic resistance phenotypes and geographic distribution. Most concerning, colistin resistance (38%) and cefiderocol resistance (10%) were common within CC2 sublineage C (CC2C), where the majority of isolates belonged to ST2 Pas /ST281 Ox . Additionally, we identified ST499 Pas as the most common non-CC2 lineage in our study. Our findings suggest a shift within the CR Ab population in the United States during the past 10 years and emphasize the importance of real-time surveillance and molecular epidemiology in studying CR Ab dissemination and clinical impact. IMPORTANCE Carbapenem-resistant Acinetobacter baumannii (CR Ab ) constitutes a major threat to public health. To elucidate the molecular and clinical epidemiology of CR Ab in the United States, clinical CR Ab isolates were collected along with data on patient characteristics and outcomes, and bacterial isolates underwent whole-genome sequencing and antibiotic susceptibility phenotyping. Key findings included emergence of new sublineages within the globally predominant clonal complex 2 (CC2), increased colistin and cefiderocol resistance within one of the CC2 sublineages, and emergence of ST499 Pas as the dominant non-CC2 CR Ab lineage in U.S. hospitals.
    Materialart: Online-Ressource
    ISSN: 2150-7511
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2022
    ZDB Id: 2557172-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    American Association for the Advancement of Science (AAAS) ; 2004
    In:  Science Vol. 306, No. 5703 ( 2004-12-10), p. 1934-1937
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 306, No. 5703 ( 2004-12-10), p. 1934-1937
    Kurzfassung: Malaria parasites secrete proteins across the vacuolar membrane into the erythrocyte, inducing modifications linked to disease and parasite survival. We identified an 11–amino acid signal required for the secretion of proteins from the Plasmodium falciparum vacuole to the human erythrocyte. Bioinformatics predicted a secretome of 〉 320 proteins and conservation of the signal across parasite species. Functional studies indicated the predictive value of the signal and its role in targeting virulence proteins to the erythrocyte and implicated its recognition by a receptor/transporter. Erythrocyte modification by the parasite may involve plasmodial heat shock proteins and be vastly more complex than hitherto realized.
    Materialart: Online-Ressource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2004
    ZDB Id: 128410-1
    ZDB Id: 2066996-3
    ZDB Id: 2060783-0
    SSG: 11
    Standort Signatur Einschränkungen Verfügbarkeit
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