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Transferrin-iron uptake by gram-negative bacteria

Cynthia Nau Cornelissen
2003 Frontiers in Bioscience  
Cornelissen, C N, J E Anderson and P F Sparling: Energy-dependent changes in the gonococcal transferrin receptor. Mol Microbiol 26, 25-35 (1997) 48.  ...  Cornelissen, C N and P F Sparling: Binding and surface exposure characteristics of the gonococcal transferrin receptor are dependent on both transferrinbinding proteins.  ... 
doi:10.2741/1076 pmid:12700102 fatcat:mtr2svwfvjfllaoeft4sjq64yq

TonB-Dependent Transporters Expressed by Neisseria gonorrhoeae

Cynthia Nau Cornelissen, Aimee Hollander
2011 Frontiers in Microbiology  
Cynthia Nau Cornelissen is also supported by the SE STI Center grant (U19 AI31496) from the National Institute of Allergy and Infectious Diseases. the best characterized of all the gonococcal TonB-dependent  ...  and Sparling, 1996; Cornelissen et al., 1997b) .  ... 
doi:10.3389/fmicb.2011.00117 pmid:21747812 pmcid:PMC3128382 fatcat:5bdtso573fblnpgczsaiggy6j4

The transferrin-iron import system from pathogenicNeisseriaspecies

Nicholas Noinaj, Susan K. Buchanan, Cynthia Nau Cornelissen
2012 Molecular Microbiology  
Other studies have also shown that the exposure of TbpB depends on TbpA, and whether or not TbpA can be energized by TonB (Cornelissen and Sparling, 1996; Cornelissen et al., 1997b) .  ...  Further, individual loops of TbpA were expressed alone and tested to see whether any retained ligand binding function (Masri and Cornelissen, 2002) .  ... 
doi:10.1111/mmi.12002 pmid:22957710 pmcid:PMC3468669 fatcat:zu6noclllnfctlyx2ekm7vfhpy

ThefbpABCOperon Is Required for Ton-Independent Utilization of Xenosiderophores byNeisseria gonorrhoeaeStrain FA19

Heather R. Strange, Tracey A. Zola, Cynthia Nau Cornelissen, S. M. Payne
2010 Infection and Immunity  
ABSTRACTNeisseria gonorrhoeaeproduces no known siderophores but can employ host-derived, iron-binding proteins, including transferrin and lactoferrin, as iron sources. Given the propensity of this pathogen to hijack rather than synthesize iron-sequestering molecules, we hypothesized that the ability to use siderophores produced by other bacteria, or xenosiderophores, may also play a role in the survival of the gonococcus. Among a panel of diverse siderophores, only the catecholate
more » ... olate xenosiderophores enterobactin and salmochelin promoted growth of gonococcal strain FA19. Surprisingly, the internalization pathway was independent of TonB or any of the TonB-dependent transporters. Xenosiderophore-mediated growth was similarly independent of the pilin-extruding secretin formed by PilQ and of the hydrophobic-agent efflux system composed of MtrCDE. ThefbpABCoperon encodes a periplasmic-binding-protein-dependent ABC transport system that enables the gonococcus to transport iron into the cell subsequent to outer membrane translocation. We hypothesized that the FbpABC proteins, required for ferric iron transport from transferrin and lactoferrin, might also contribute to the utilization of xenosiderophores as iron sources. We created mutants that conditionally expressed FbpABC from an IPTG-inducible promoter. We determined that expression of FbpABC was required for growth of gonococcal strain FA19 in the presence of enterobactin and salmochelin. The monomeric component of enterobactin, dihydroxybenzoylserine (DHBS), and the S2 form of salmochelin specifically promoted FbpABC-dependent growth of FA19. This study demonstrated that the gonococcal FbpABC transport system is required for utilization of some xenosiderophores as iron sources and that growth promotion by these ferric siderophores can occur in the absence of TonB or individual TonB-dependent transporters.
doi:10.1128/iai.00807-10 pmid:21041493 pmcid:PMC3019921 fatcat:wy7xflybpzcc5lia7uv2aimfoq

Kinetic analysis of ligand interaction with the gonococcal transferrin-iron acquisition system

Amanda J. DeRocco, Mary Kate Yost-Daljev, Christopher D. Kenney, Cynthia Nau Cornelissen
2008 Biometals  
and Cornelissen 2007; Noto and Cornelissen 2008) .  ...  In contrast, TbpB is a surface exposed lipoprotein (Irwin, Averil et al. 1993; Lissolo, Maitre-Wilmotte et al. 1995; Cornelissen and Sparling 1996; Renauld-Mongenie, Poncet et al. 1997; DeRocco and Cornelissen  ... 
doi:10.1007/s10534-008-9179-y pmid:19048191 pmcid:PMC2682638 fatcat:ppvnqcmydfbhxhl5nzde2h7p5u

Beyond the Crystal Structure: Insight into the Function and Vaccine Potential of TbpA Expressed by Neisseria gonorrhoeae

Devin R. Cash, Nicholas Noinaj, Susan K. Buchanan, Cynthia Nau Cornelissen, C. R. Roy
2015 Infection and Immunity  
ABSTRACTNeisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, is not preventable by vaccination and is rapidly developing resistance to antibiotics. However, the transferrin (Tf) receptor system, composed of TbpA and TbpB, is an ideal target for novel therapeutics and vaccine development. Using a three-dimensional structure of gonococcal TbpA, we investigated two hypotheses, i.e., that loop-derived antibodies can interrupt ligand-receptor interactions in
more » ... interactions in the native bacterium and that the loop 3 helix is a critical functional domain. Preliminary loop-derived antibodies, as well as optimized second-generation antibodies, demonstrated similar modest ligand-blocking effects on the gonococcal surface but different effects inEscherichia coli. Mutagenesis of loop 3 helix residues was employed, generating 11 mutants. We separately analyzed the mutants' abilities to (i) bind Tf and (ii) internalize Tf-bound iron in the absence of the coreceptor TbpB. Single residue mutations resulted in up to 60% reductions in ligand binding and up to 85% reductions in iron utilization. All strains were capable of growing on Tf as the sole iron source. Interestingly, in the presence of TbpB, only a 30% reduction in Tf-iron utilization was observed, indicating that the coreceptor can compensate for TbpA impairment. Complete deletion of the loop 3 helix of TbpA eliminated the abilities to bind Tf, internalize iron, and grow with Tf as the sole iron source. Our studies demonstrate that while the loop 3 helix is a key functional domain, its function does not exclusively rely on any single residue.
doi:10.1128/iai.00762-15 pmid:26351283 pmcid:PMC4598392 fatcat:hpys4o4vlvcptdzce5zl5ggofy

The Iron-Repressed, AraC-Like Regulator MpeR Activates Expression offetAin Neisseria gonorrhoeae

Aimee Hollander, Alexandra Dubon Mercante, William M. Shafer, Cynthia Nau Cornelissen, S. M. Payne
2011 Infection and Immunity  
ABSTRACTNeisseria gonorrhoeaeis an obligate human pathogen that causes the common sexually transmitted infection gonorrhea. Gonococcal infections cause significant morbidity, particularly among women, as the organism ascends to the upper reproductive tract, resulting in pelvic inflammatory disease, ectopic pregnancy, and infertility. In the last few years, antibiotic resistance rates have risen dramatically, leading to severe restriction of treatment options for gonococcal disease. Gonococcal
more » ... sease. Gonococcal infections do not elicit protective immunity, nor is there an effective vaccine to prevent the disease. Thus, further understanding of the expression, function, and regulation of surface antigens could lead to better treatment and prevention modalities in the future. In the current study, we determined that an iron-repressed regulator, MpeR, interacted specifically with the DNA sequence upstream offetAand activated FetA expression. Interestingly, MpeR was previously shown to regulate the expression of gonococcal antimicrobial efflux systems. We confirmed that the outer membrane transporter FetA allows gonococcal strain FA1090 to utilize the xenosiderophore ferric enterobactin as an iron source. However, we further demonstrated that FetA has an extended range of substrates that encompasses other catecholate xenosiderophores, including ferric salmochelin and the dimers and trimers of dihydroxybenzoylserine. We demonstrated thatfetAis part of an iron-repressed, MpeR-activated operon which putatively encodes other iron transport proteins. This is the first study to describe a regulatory linkage between antimicrobial efflux and iron transport inN. gonorrhoeae. The regulatory nidus that links these systems, MpeR, is expressed exclusively by pathogenic neisseriae and is therefore expected to be an important virulence factor.
doi:10.1128/iai.05806-11 pmid:21947770 pmcid:PMC3232672 fatcat:66da425yqjcbddowjk3deunafy

Structural Basis for Evasion of Nutritional Immunity by the Pathogenic Neisseriae

Ravi Yadav, Nicholas Noinaj, Nicholas Ostan, Trevor Moraes, Julie Stoudenmire, Stavros Maurakis, Cynthia Nau Cornelissen
2020 Frontiers in Microbiology  
TbpA is very well conserved (Cornelissen et al., 2000) and not subject to high-frequency phase or antigenic variation.  ...  We demonstrated that mutagenesis of the TonB-box abrogated transport function while preserving transferrin-binding capabilities (Kenney and Cornelissen, 2002) .  ... 
doi:10.3389/fmicb.2019.02981 pmid:31998268 pmcid:PMC6965322 fatcat:4lpdwqctvfaspajhruf3eko2eq

Gonococcal transferrin binding protein chimeras induce bactericidal and growth inhibitory antibodies in mice

Gregory A. Price, Heather P. Masri, Aimee M. Hollander, Michael W. Russell, Cynthia Nau Cornelissen
2007 Vaccine  
We have previously demonstrated the full-length gonococcal transferrin binding proteins (TbpA and TbpB) to be promising antigens in the development of a protective vaccine against Neisseria gonorrhoeae. In the current study we employed a genetic chimera approach fusing domains from TbpA and TbpB to the A2 domain of cholera toxin, which naturally binds in a non-covalent fashion to the B subunit of cholera toxin during assembly. For one construct, the N-terminal half of TbpB (NB) was fused to the
more » ... B) was fused to the A2 subunit of cholera toxin. In a second construct, the loop 2 region (L2) of TbpA was genetically fused between the NB domain and the A2 domain, generating a double chimera. Both chimeras were immunogenic and induced serum bactericidal and vaginal growthinhibiting antibodies. This study highlights the potential of using protective epitopes instead of fulllength proteins in the development of an efficacious gonococcal vaccine.
doi:10.1016/j.vaccine.2007.07.038 pmid:17720283 pmcid:PMC2225598 fatcat:464jy6xvkzbhbcgoj7wo5ym4ym

Conserved Regions of Gonococcal TbpB Are Critical for Surface Exposure and Transferrin Iron Utilization

Karen L. Ostberg, Amanda J. DeRocco, Shreni D. Mistry, Mary Kathryne Dickinson, Cynthia Nau Cornelissen, S. M. Payne
2013 Infection and Immunity  
ABSTRACTThe transferrin-binding proteins TbpA and TbpB enableNeisseria gonorrhoeaeto obtain iron from human transferrin. The lipoprotein TbpB facilitates, but is not strictly required for, TbpA-mediated iron acquisition. The goal of the current study was to determine the contribution of two conserved regions within TbpB to the function of this protein. Using site-directed mutagenesis, the first mutation we constructed replaced the lipobox (LSAC) of TbpB with a signal I peptidase cleavage site
more » ... ase cleavage site (LAAA), while the second mutation deleted a conserved stretch of glycine residues immediately downstream of the lipobox. We then evaluated the resulting mutants for effects on TbpB expression, surface exposure, and transferrin iron utilization. Western blot analysis and palmitate labeling indicated that the lipobox, but not the glycine-rich motif, is required for lipidation of TbpB and tethering to the outer membrane. TbpB was released into the supernatant by the mutant that produces TbpB LSAC. Neither mutation disrupted the transport of TbpB across the bacterial cell envelope. When these mutant TbpB proteins were produced in a strain expressing a form of TbpA that requires TbpB for iron acquisition, growth on transferrin was either abrogated or dramatically diminished. We conclude that surface tethering of TbpB is required for optimal performance of the transferrin iron acquisition system, while the presence of the polyglycine stretch near the amino terminus of TbpB contributes significantly to transferrin iron transport function. Overall, these results provide important insights into the functional roles of two conserved motifs of TbpB, enhancing our understanding of this critical iron uptake system.
doi:10.1128/iai.00280-13 pmid:23836816 pmcid:PMC3754215 fatcat:nvhbpxnsyzaerlcq2x4qj5thw4

The Novel Interaction Between Neisseria gonorrhoeae TdfJ and Human S100A7 Allows Gonococci to Subvert Host Zinc Restriction

Stavros Maurakis, Kayla Keller, C. Noel Maxwell, Kevin Pereira, Walter J. Chazin, Alison K. Criss, Cynthia Nau Cornelissen, Christoph Tang
2019 PLoS Pathogens  
Criss, Cynthia Nau Cornelissen.  ...  Criss, Cynthia Nau Cornelissen. Formal analysis: Stavros Maurakis, Cynthia Nau Cornelissen. Fig 1 . 1 Fig 1.  ... 
doi:10.1371/journal.ppat.1007937 pmid:31369630 pmcid:PMC6692053 fatcat:ncyklyxwxrhwdntf656qy6u74y

Molecular Insight into TdfH-Mediated Zinc Piracy from Human Calprotectin by Neisseria gonorrhoeae

Michael T. Kammerman, Aloke Bera, Runrun Wu, Simone A. Harrison, C. Noel Maxwell, Karl Lundquist, Nicholas Noinaj, Walter J. Chazin, Cynthia Nau Cornelissen, Nancy E. Freitag
2020 mBio  
We thank members of the Cornelissen laboratory, particularly Julie Stoudenmire, for critical reading of the manuscript.  ... 
doi:10.1128/mbio.00949-20 pmid:32457249 fatcat:evmiuxykufhnrduuykyc3itxbe