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Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan
Publication . Gonçalves, Barbara V.; Portela, Raquel; Lobo, Ricardo; Figueiredo, Teresa A.; Grilo, Inês R.; Ludovice, Ana Madalena; de Lencastre, Herminia; Dias, Jorge S.; Sobral, Rita G.; DCV - Departamento de Ciências da Vida; UCIBIO - Applied Molecular Biosciences Unit; Instituto de Tecnologia Química e Biológica António Xavier (ITQB); Molecular, Structural and Cellular Microbiology (MOSTMICRO); DQ - Departamento de Química; American Society for Microbiology
Glutamate amidation, a secondary modification of the peptidoglycan, was first identified in Staphylococcus aureus. It is catalyzed by the protein products of the murT and gatD genes, which are conserved and colocalized in the genomes of most sequenced Gram-positive bacterial species. The MurT-GatD complex is required for cell viability, full resistance to β-lactam antibiotics, and resistance to human lysozyme and is recognized as an attractive target for new antimicrobials. Great effort has been invested in the study of this step, culminating recently in three independent reports addressing the structural elucidation of the MurT-GatD complex. In this work, we demonstrate through the use of nonstructural approaches the critical and multiple roles of the C-terminal domain of MurT, annotated as DUF1727, in the MurT-GatD enzymatic complex. This domain provides the physical link between the two enzymatic activities and is essential for the amidation reaction. Copurification of recombinant MurT and GatD proteins and bacterial two-hybrid assays support the observation that the MurT-GatD interaction occurs through this domain. Most importantly, we provide in vivo evidence of the effect of substitutions at specific residues in DUF1727 on cell wall peptidoglycan amidation and on the phenotypes of oxacillin resistance and bacterial growth.
Unfolding the physiological roles of the binding of Atl to eDNA in Staphylococcus aureus
Publication . Grilo, Maria Inês Ramos; Lencastre, Hermínia; Ludovice, Ana Madalena; Sobral, Rita
Staphylococcus aureus is usually a commensal organism of the human’s
microbiota, although it can become invasive when the host’s defenses are
breached, becoming an important nosocomial opportunistic pathogen, with
high morbidity and mortality rates across the globe. It is responsible for a wide
array of infections that range from minor skin and soft tissue infections to
more severe ones, such as endocarditis, osteomyelitis and sepsis. This
microorganism harbors a plethora of virulence factors that alongside its
capacity to acquire resistance to virtually all antibiotics have enabled it to
become one of the most prominent pathogens of this era. In fact, S. aureus is
one of the major causes for infections associated with indwelling devices,
which are usually related with biofilm development. Biofilms are multicellular
sessile microbial communities in which cells are attached to a surface and/or
to other cells and encased within a self-produced protective extracellular
matrix. The biofilm forming capacity of S. aureus is part of the myriad of
virulence mechanisms that enables this bacterium to resist both antibiotic
treatment and the action of the host immune system.
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Fundação para a Ciência e a Tecnologia
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SFRH
Número da atribuição
SFRH/BD/70162/2010