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North Decatur, GA, United States

Hollander A.,Virginia Commonwealth University | Mercante A.D.,Emory University | Shafer W.M.,Emory University | Shafer W.M.,Medical Center Atlanta | Cornelissen C.N.,Virginia Commonwealth University
Infection and Immunity | Year: 2011

Neisseria gonorrhoeae is 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 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 of fetA and 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 that fetA is 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 in N. 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. © 2011, American Society for Microbiology. Source

Johnson P.J.T.,Emory University | Stringer V.A.,Emory University | Shafer W.M.,Emory University | Shafer W.M.,Medical Center Atlanta
Antimicrobial Agents and Chemotherapy | Year: 2011

DNA-binding proteins that control expression of drug efflux pump genes have been termed "local regulators" as their encoding gene is often located adjacent to the gene(s) that they regulate. However, results from recent studies indicate that they can control genes outside efflux pump-encoding loci, which we term as being "off target." For example, the MtrR repressor was initially recognized for its ability to repress transcription of the mtrCDE-encoded efflux pump operon in the strict human pathogen Neisseria gonorrhoeae, but recent results from genetic and microarray studies have shown that it can control expression of nearly 70 genes scattered throughout the chromosome. One of the off-target MtrR-repressed genes is glnA, which encodes glutamine synthetase. Herein, we confirm the capacity of MtrR to repress glnA expression and provide evidence that such repression is due to its ability to negatively influence the binding of a second DNA-binding protein (FarR), which activates glnA. FarR was previously recognized as a transcriptional repressor of the farAB-encoded efflux pump operon. Thus, two DNA-binding proteins previously characterized as repressors of genes encoding efflux pumps that contribute to gonococcal resistance to antimicrobials can act in an opposing manner to modulate expression of a gene involved in basic metabolism. Copyright © 2011, American Society for Microbiology. All Rights Reserved. Source

Ready D.J.,Medical Center Atlanta | Ready D.J.,Emory University | Gerardi R.J.,Medical Center Atlanta | Backscheider A.G.,University of Houston | And 2 more authors.
Cyberpsychology, Behavior, and Social Networking | Year: 2010

Eleven Vietnam veterans with war-related posttraumatic stress disorder (PTSD) were randomly assigned to 10 sessions of either virtual reality exposure (VRE) therapy within a computer-generated virtual Vietnam environment or present-centered therapy (PCT) that avoided traumatic content and utilized a problem-solving approach. Participants were assessed at pretreatment, posttreatment, and 6 months posttreatment by an independent assessor blind to treatment condition. Nine participants completed treatment with one dropout per condition. No significant differences emerged between treatments, likely due to insufficient power. Although comparison of mean changes in PTSD symptoms for the VRE and PCT conditions yielded a moderate effect size (d=0.56) in favor of VRE at 6 months posttreatment, changes in PTSD scores were more variable, and therefore less reliable, within the VRE condition. The utility of VRE with older veterans with PTSD is discussed. © Copyright 2010, Mary Ann Liebert, Inc. 2010. Source

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