The Gonococcal Fur-Regulated tbpA and tbpB Genes Are Expressed during Natural Mucosal Gonococcal Infection

Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, 650 Albany Street, Room 637, Boston, Massachusetts 02118, USA.
Infection and Immunity (Impact Factor: 3.73). 08/2005; 73(7):4281-7. DOI: 10.1128/IAI.73.7.4281-4287.2005
Source: PubMed


Iron is limiting in the human host, and bacterial pathogens respond to this environment by regulating gene expression through
the ferric uptake regulator protein (Fur). In vitro studies have demonstrated that Neisseria gonorrhoeae controls the expression of several critical genes through an iron- and Fur-mediated mechanism. While most in vitro experiments
are designed to determine the response of N. gonorrhoeae to an exogenous iron concentration of zero, these organisms are unlikely to be exposed to such severe limitations of iron
in vivo. To determine if N. gonorrhoeae expresses iron- and Fur-regulated genes in vivo during uncomplicated gonococcal infection, we examined gene expression profiles
of specimens obtained from male subjects with urethral infections. RNA was isolated from urethral swab specimens and used
as a template to amplify, by reverse transcriptase PCR (RT-PCR), gonococcal genes known to be regulated by iron and Fur (tbpA, tbpB, and fur). The constitutively expressed gonococcal rmp gene was used as a positive control. RT-PCR analysis indicated that gonorrhea-positive specimens where rmp expression was seen were also 93% (51/55) fbpA positive, 87% (48/55) tbpA positive, and 86% (14 of 16 tested) tbpB positive. In addition, we detected a fur transcript in 79% (37 of 47 tested) of positive specimens. We also measured increases in levels of immunoglobulin G antibody
against TbpA (91%) and TbpB (73%) antigens in sera from infected male subjects compared to those in uninfected controls. A
positive trend between tbpA gene expression and TbpA antibody levels in sera indicated a relationship between levels of gene expression and immune response
in male subjects infected with gonorrhea for the first time. These results indicate that gonococcal iron- and Fur-regulated
tbpA and tbpB genes are expressed in gonococcal infection and that male subjects with mucosal gonococcal infections exhibit antibodies
to these proteins.

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Available from: Lee M Wetzler, Oct 09, 2015
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    • "These antibody levels were well below those associated with a protective response, as was detected against tetanus toxoid. While the Tbps are clearly expressed in vivo (Agarwal et al., 2005), the mere presence of these proteins within the context of a natural infection is insufficient to initiate a high-titer, protective immune response (Price et al., 2004), consistent with the lack of immunity following natural infections. "
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