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  1. Article ; Online: CanB is a metabolic mediator of antibiotic resistance in Neisseria gonorrhoeae.

    Rubin, Daniel H F / Ma, Kevin C / Westervelt, Kathleen A / Hullahalli, Karthik / Waldor, Matthew K / Grad, Yonatan H

    Nature microbiology

    2023  Volume 8, Issue 1, Page(s) 28–39

    Abstract: The evolution of the obligate human pathogen Neisseria gonorrhoeae has been shaped by selective pressures from diverse host niche environments and antibiotics. The varying prevalence of antibiotic resistance across N. gonorrhoeae lineages suggests that ... ...

    Abstract The evolution of the obligate human pathogen Neisseria gonorrhoeae has been shaped by selective pressures from diverse host niche environments and antibiotics. The varying prevalence of antibiotic resistance across N. gonorrhoeae lineages suggests that underlying metabolic differences may influence the likelihood of acquisition of specific resistance mutations. We hypothesized that the requirement for supplemental CO
    MeSH term(s) Humans ; Neisseria gonorrhoeae/genetics ; Gonorrhea ; Genome-Wide Association Study ; Carbon Dioxide ; Drug Resistance, Microbial/genetics ; Ciprofloxacin/pharmacology
    Chemical Substances Carbon Dioxide (142M471B3J) ; Ciprofloxacin (5E8K9I0O4U)
    Language English
    Publishing date 2023-01-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-022-01282-x
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  2. Article ; Online: CRISPR-mediated germline mutagenesis for genetic sterilization of Anopheles gambiae males.

    Smidler, Andrea L / Marrogi, Eryney / Kauffman, Jamie / Paton, Douglas G / Westervelt, Kathleen A / Church, George M / Esvelt, Kevin M / Shaw, W Robert / Catteruccia, Flaminia

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 4057

    Abstract: Rapid spread of insecticide resistance among anopheline mosquitoes threatens malaria elimination efforts, necessitating development of alternative vector control technologies. Sterile insect technique (SIT) has been successfully implemented in multiple ... ...

    Abstract Rapid spread of insecticide resistance among anopheline mosquitoes threatens malaria elimination efforts, necessitating development of alternative vector control technologies. Sterile insect technique (SIT) has been successfully implemented in multiple insect pests to suppress field populations by the release of large numbers of sterile males, yet it has proven difficult to adapt to Anopheles vectors. Here we outline adaptation of a CRISPR-based genetic sterilization system to selectively ablate male sperm cells in the malaria mosquito Anopheles gambiae. We achieve robust mosaic biallelic mutagenesis of zero population growth (zpg, a gene essential for differentiation of germ cells) in F1 individuals after intercrossing a germline-expressing Cas9 transgenic line to a line expressing zpg-targeting gRNAs. Approximately 95% of mutagenized males display complete genetic sterilization, and cause similarly high levels of infertility in their female mates. Using a fluorescence reporter that allows detection of the germline leads to a 100% accurate selection of spermless males, improving the system. These males cause a striking reduction in mosquito population size when released at field-like frequencies in competition cages against wild type males. These findings demonstrate that such a genetic system could be adopted for SIT against important malaria vectors.
    MeSH term(s) Humans ; Animals ; Male ; Female ; Anopheles/genetics ; Mosquito Control/methods ; Mosquito Vectors/genetics ; Semen ; RNA, Guide, CRISPR-Cas Systems ; Infertility, Male/genetics ; Malaria ; Mutagenesis ; Germ Cells
    Chemical Substances RNA, Guide, CRISPR-Cas Systems
    Language English
    Publishing date 2024-02-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-54498-8
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  3. Article ; Online: A Genome-Scale Antibiotic Screen in Serratia marcescens Identifies YdgH as a Conserved Modifier of Cephalosporin and Detergent Susceptibility.

    Lazarus, Jacob E / Warr, Alyson R / Westervelt, Kathleen A / Hooper, David C / Waldor, Matthew K

    Antimicrobial agents and chemotherapy

    2021  Volume 65, Issue 12, Page(s) e0078621

    Abstract: Serratia marcescens, a member of the order Enterobacterales, is adept at colonizing health care environments and is an important cause of invasive infections. Antibiotic resistance is a daunting problem in S. marcescens because, in addition to plasmid- ... ...

    Abstract Serratia marcescens, a member of the order Enterobacterales, is adept at colonizing health care environments and is an important cause of invasive infections. Antibiotic resistance is a daunting problem in S. marcescens because, in addition to plasmid-mediated mechanisms, most isolates have considerable intrinsic resistance to multiple antibiotic classes. To discover endogenous modifiers of antibiotic susceptibility in S. marcescens, a high-density transposon insertion library was subjected to sub-MICs of two cephalosporins, cefoxitin, and cefepime, as well as the fluoroquinolone ciprofloxacin. Comparisons of transposon insertion abundance before and after antibiotic exposure identified hundreds of potential modifiers of susceptibility to these agents. Using single-gene deletions, we validated several candidate modifiers of cefoxitin susceptibility and chose
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Cephalosporins/pharmacology ; Detergents/pharmacology ; Drug Resistance, Bacterial ; Serratia marcescens/drug effects ; Serratia marcescens/genetics
    Chemical Substances Anti-Bacterial Agents ; Cephalosporins ; Detergents
    Language English
    Publishing date 2021-09-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.00786-21
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 809: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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    Einzelsignatur: Show issues

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  4. Article ; Online: The

    Wood, Thomas E / Westervelt, Kathleen A / Yoon, Jessica M / Eshleman, Heather D / Levy, Roie / Burnes, Henry / Slade, Daniel J / Lesser, Cammie F / Goldberg, Marcia B

    mBio

    2022  Volume 13, Issue 3, Page(s) e0127022

    Abstract: The type III secretion system is required for virulence of many pathogenic bacteria. Bacterial effector proteins delivered into target host cells by this system modulate host signaling pathways and processes in a manner that promotes infection. Here, we ... ...

    Abstract The type III secretion system is required for virulence of many pathogenic bacteria. Bacterial effector proteins delivered into target host cells by this system modulate host signaling pathways and processes in a manner that promotes infection. Here, we define the activity of the effector protein OspB of the human pathogen
    MeSH term(s) Animals ; Arginine/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Cysteine/metabolism ; Cysteine Proteases/genetics ; Cysteine Proteases/metabolism ; Dysentery, Bacillary ; Histidine/metabolism ; Mammals/metabolism ; Mechanistic Target of Rapamycin Complex 1 ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Shigella/physiology ; Shigella flexneri/metabolism ; Type III Secretion Systems/genetics ; Type III Secretion Systems/metabolism
    Chemical Substances Bacterial Proteins ; Type III Secretion Systems ; Histidine (4QD397987E) ; Arginine (94ZLA3W45F) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Cysteine Proteases (EC 3.4.-) ; Cysteine (K848JZ4886)
    Language English
    Publishing date 2022-05-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.01270-22
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  5. Article ; Online: The wavy Mutation Maps to the Inositol 1,4,5-Trisphosphate 3-Kinase 2 (IP3K2) Gene of Drosophila and Interacts with IP3R to Affect Wing Development.

    Dean, Derek M / Maroja, Luana S / Cottrill, Sarah / Bomkamp, Brent E / Westervelt, Kathleen A / Deitcher, David L

    G3 (Bethesda, Md.)

    2015  Volume 6, Issue 2, Page(s) 299–310

    Abstract: Inositol 1,4,5-trisphosphate (IP3) regulates a host of biological processes from egg activation to cell death. When IP3-specific receptors (IP3Rs) bind to IP3, they release calcium from the ER into the cytoplasm, triggering a variety of cell type- and ... ...

    Abstract Inositol 1,4,5-trisphosphate (IP3) regulates a host of biological processes from egg activation to cell death. When IP3-specific receptors (IP3Rs) bind to IP3, they release calcium from the ER into the cytoplasm, triggering a variety of cell type- and developmental stage-specific responses. Alternatively, inositol polyphosphate kinases can phosphorylate IP3; this limits IP3R activation by reducing IP3 levels, and also generates new signaling molecules altogether. These divergent pathways draw from the same IP3 pool yet cause very different cellular responses. Therefore, controlling the relative rates of IP3R activation vs. phosphorylation of IP3 is essential for proper cell functioning. Establishing a model system that sensitively reports the net output of IP3 signaling is crucial for identifying the controlling genes. Here we report that mutant alleles of wavy (wy), a classic locus of the fruit fly Drosophila melanogaster, map to IP3 3-kinase 2 (IP3K2), a member of the inositol polyphosphate kinase gene family. Mutations in wy disrupt wing structure in a highly specific pattern. RNAi experiments using GAL4 and GAL80(ts) indicated that IP3K2 function is required in the wing discs of early pupae for normal wing development. Gradations in the severity of the wy phenotype provide high-resolution readouts of IP3K2 function and of overall IP3 signaling, giving this system strong potential as a model for further study of the IP3 signaling network. In proof of concept, a dominant modifier screen revealed that mutations in IP3R strongly suppress the wy phenotype, suggesting that the wy phenotype results from reduced IP4 levels, and/or excessive IP3R signaling.
    MeSH term(s) Alleles ; Animals ; Base Sequence ; Chromosome Mapping ; Drosophila/genetics ; Drosophila/growth & development ; Drosophila/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Epistasis, Genetic ; Gene Order ; Inositol 1,4,5-Trisphosphate Receptors/genetics ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Models, Biological ; Molecular Sequence Data ; Mutation ; Phenotype ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Protein Binding ; Quantitative Trait Loci ; RNA Interference ; Signal Transduction ; Wings, Animal/growth & development ; Wings, Animal/metabolism
    Chemical Substances Drosophila Proteins ; Inositol 1,4,5-Trisphosphate Receptors ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; inositol 1,4,5-trisphosphate kinase 2, Drosophila (EC 2.7.1.127)
    Language English
    Publishing date 2015-11-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1534/g3.115.024307
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  6. Article ; Online: Steroid Hormone Function Controls Non-competitive Plasmodium Development in Anopheles.

    Werling, Kristine / Shaw, W Robert / Itoe, Maurice A / Westervelt, Kathleen A / Marcenac, Perrine / Paton, Douglas G / Peng, Duo / Singh, Naresh / Smidler, Andrea L / South, Adam / Deik, Amy A / Mancio-Silva, Liliana / Demas, Allison R / March, Sandra / Calvo, Eric / Bhatia, Sangeeta N / Clish, Clary B / Catteruccia, Flaminia

    Cell

    2019  Volume 177, Issue 2, Page(s) 315–325.e14

    Abstract: Transmission of malaria parasites occurs when a female Anopheles mosquito feeds on an infected host to acquire nutrients for egg development. How parasites are affected by oogenetic processes, principally orchestrated by the steroid hormone 20- ... ...

    Abstract Transmission of malaria parasites occurs when a female Anopheles mosquito feeds on an infected host to acquire nutrients for egg development. How parasites are affected by oogenetic processes, principally orchestrated by the steroid hormone 20-hydroxyecdysone (20E), remains largely unknown. Here we show that Plasmodium falciparum development is intimately but not competitively linked to processes shaping Anopheles gambiae reproduction. We unveil a 20E-mediated positive correlation between egg and oocyst numbers; impairing oogenesis by multiple 20E manipulations decreases parasite intensities. These manipulations, however, accelerate Plasmodium growth rates, allowing sporozoites to become infectious sooner. Parasites exploit mosquito lipids for faster growth, but they do so without further affecting egg development. These results suggest that P. falciparum has adopted a non-competitive evolutionary strategy of resource exploitation to optimize transmission while minimizing fitness costs to its mosquito vector. Our findings have profound implications for currently proposed control strategies aimed at suppressing mosquito populations.
    MeSH term(s) Animals ; Anopheles/parasitology ; Culicidae ; Ecdysterone/metabolism ; Ecdysterone/physiology ; Female ; HEK293 Cells ; Host-Parasite Interactions/physiology ; Humans ; Insect Vectors ; Malaria/parasitology ; Malaria, Falciparum/parasitology ; Mice ; Mosquito Vectors ; NIH 3T3 Cells ; Oogenesis/physiology ; Plasmodium/metabolism ; Plasmodium falciparum ; Sporozoites ; Steroids/metabolism
    Chemical Substances Steroids ; Ecdysterone (5289-74-7)
    Language English
    Publishing date 2019-03-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2019.02.036
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    Zs.A 1167: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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  7. Article: Steroid Hormone Function Controls Non-competitive Plasmodium Development in Anopheles

    Werling, Kristine / Shaw, W. Robert / Itoe, Maurice A / Westervelt, Kathleen A / Marcenac, Perrine / Paton, Douglas G / Peng, Duo / Singh, Naresh / Smidler, Andrea L / South, Adam / Deik, Amy A / Mancio-Silva, Liliana / Demas, Allison R / March, Sandra / Calvo, Eric / Bhatia, Sangeeta N / Clish, Clary B / Catteruccia, Flaminia

    Elsevier Inc. Cell. 2019 Apr. 04, v. 177, no. 2

    2019  

    Abstract: Transmission of malaria parasites occurs when a female Anopheles mosquito feeds on an infected host to acquire nutrients for egg development. How parasites are affected by oogenetic processes, principally orchestrated by the steroid hormone 20- ... ...

    Abstract Transmission of malaria parasites occurs when a female Anopheles mosquito feeds on an infected host to acquire nutrients for egg development. How parasites are affected by oogenetic processes, principally orchestrated by the steroid hormone 20-hydroxyecdysone (20E), remains largely unknown. Here we show that Plasmodium falciparum development is intimately but not competitively linked to processes shaping Anopheles gambiae reproduction. We unveil a 20E-mediated positive correlation between egg and oocyst numbers; impairing oogenesis by multiple 20E manipulations decreases parasite intensities. These manipulations, however, accelerate Plasmodium growth rates, allowing sporozoites to become infectious sooner. Parasites exploit mosquito lipids for faster growth, but they do so without further affecting egg development. These results suggest that P. falciparum has adopted a non-competitive evolutionary strategy of resource exploitation to optimize transmission while minimizing fitness costs to its mosquito vector. Our findings have profound implications for currently proposed control strategies aimed at suppressing mosquito populations.
    Keywords Anopheles gambiae ; Plasmodium falciparum ; ecdysterone ; eggs ; females ; insect vectors ; malaria ; nutrients ; oocysts ; oogenesis ; parasites ; sporozoites ; steroid hormones
    Language English
    Dates of publication 2019-0404
    Size p. 315-325.e14.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2019.02.036
    Database NAL-Catalogue (AGRICOLA)

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