J. Hiroshi Morisaki

A homogeneous high-DAR antibody–drug conjugate platform combining THIOMAB antibodies and XTEN polypeptides

Neelie T. Zacharias, Vladimir N. Podust, Kimberly K. Kajihara, Douglas D. Leipold et autres

Efficiency of targeted cell delivery of small molecules was enhanced in cells and animals via a novel well-defined bioconjugation platform combining site-specific antibody conjugation and XTEN polypeptides to enable high payload loading.

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A homogeneous high-DAR antibody-drug conjugate platform combining THIOMABTM antibodies and XTEN polypeptides

Neelie T. Zacharias, Vladimir N. Podust, Kimberly K. Kajihara, Douglas D. Leipold et autres

Abstract Antibody-drug conjugates (ADCs) enable cell-specific delivery of small molecules and are validated anti-cancer therapeutics. One factor limiting ADC advancement and broader application is the drug-to-antibody ratio (DAR), which dictates the number of payloads that can be delivered per antibody. With few …

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A Putative Bacterial ABC Transporter Circumvents the Essentiality of Signal Peptidase

J. Hiroshi Morisaki, Peter A. Smith, Shailesh V. Date, Kimberly K. Kajihara et autres

UNLABELLED: The type I signal peptidase of Staphylococcus aureus, SpsB, is an attractive antibacterial target because it is essential for viability and extracellularly accessible. We synthesized compound 103, a novel arylomycin-derived inhibitor of SpsB with significant potency against various clinical S. aureus …

Novel antibody–antibiotic conjugate eliminates intracellular S. aureus

Sophie M. Lehar, Thomas H. Pillow, Min Xu, Leanna R. Staben et autres

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Global Gene Expression of Methicillin-resistant Staphylococcus aureus USA300 During Human and Mouse Infection

Shailesh V. Date, Zora Modrušan, Michael Lawrence, J. Hiroshi Morisaki et autres

Little is known about the expression of methicillin-resistant Staphylococcus aureus (MRSA) genes during infection conditions. Here, we described the transcriptome of the clinical MRSA strain USA300 derived from human cutaneous abscesses, and compared it with USA300 bacteria derived from infected kidneys in …

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Novel Staphylococcal Glycosyltransferases SdgA and SdgB Mediate Immunogenicity and Protection of Virulence-Associated Cell Wall Proteins

Wouter L. W. Hazenbos, Kimberly K. Kajihara, Richard Vandlen, J. Hiroshi Morisaki et autres

Infection of host tissues by Staphylococcus aureus and S. epidermidis requires an unusual family of staphylococcal adhesive proteins that contain long stretches of serine-aspartate dipeptide-repeats (SDR). The prototype member of this family is clumping factor A (ClfA), a key virulence factor that …

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Conserved Mechanisms of Mycobacterium marinum Pathogenesis within the Environmental Amoeba Acanthamoeba castellanii

George M. Kennedy, J. Hiroshi Morisaki, Patricia A. Champion

Mycobacterium marinum is a waterborne mycobacterial pathogen. Due to their common niche, protozoa likely represent natural hosts for M. marinum. We demonstrate that the ESX-1 secretion system is required for M. marinum pathogenesis and that M. marinum utilizes actin-based motility in amoebae. …

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ESX-1-dependent cytolysis in lysosome secretion and inflammasome activation during mycobacterial infection

Ingrid Chou Koo, Chen Wang, Sridharan Raghavan, J. Hiroshi Morisaki et autres

Exocytosis of lysosomes from macrophages has been described as a response to microbial cytotoxins and haemolysins, as well as for releasing pro-inflammatory cytokines interleukin (IL)-1beta and IL-18 during inflammasome activation. The mycobacterial ESX-1 secretion system, encoded in part by the Region of …

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Role for lysosomal enzyme β-hexosaminidase in the control of mycobacteria infection

Ingrid Chou Koo, Yamini M. Ohol, Ping Wu, J. Hiroshi Morisaki et autres

The pathogenic mycobacteria that cause tuberculosis (TB) and TB-like diseases in humans and animals elude sterilizing immunity by residing within an intracellular niche in host macrophages, where they are protected from microbicidal attack. Recent studies have emphasized microbial mechanisms for evasion of …

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Role of the WASP family proteins for Mycobacterium marinum actin tail formation

Luisa M. Stamm, Melissa A. Pak, J. Hiroshi Morisaki, Scott B. Snapper et autres

Mycobacterium marinum, a natural pathogen of fish and frogs and an occasional pathogen of humans, is capable of inducing actin tail formation within the cytoplasm of macrophages, leading to actin-based motility and intercellular spread. Actin tail formation by M. marinum is markedly …

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Mycobacterium marinum Escapes from Phagosomes and Is Propelled by Actin-based Motility

Luisa M. Stamm, J. Hiroshi Morisaki, Lian‐Yong Gao, Robert L. Jeng et autres

Mycobacteria are responsible for a number of human and animal diseases and are classical intracellular pathogens, living inside macrophages rather than as free-living organisms during infection. Numerous intracellular pathogens, including Listeria monocytogenes, Shigella flexneri, and Rickettsia rickettsii, exploit the host cytoskeleton by …

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Mycobacterium marinum escapes from phagosomes and is propelled by actin-based motility - eScholarship

Luisa M. Stamm, J. Hiroshi Morisaki, Lian‐Yong Gao, Robert L. Jeng et autres

Mycobacteria are responsible for a number of human and animal diseases and are classical intracellular pathogens, living inside macrophages rather than as free-living organisms during infection. Numerous intracellular pathogens, including Listeria monocytegenes, Shigella flexneri, and Rickettsia rickettsii, exploit the host cytoskeleton by …