Abstract
Neisseria gonorrhoeae, the causative agent of gonorrhea, is an exclusive human pathogen whose growing antibiotic resistance is causing worldwide concern. The increasing rise of antibiotic resistance expressed by gonococci highlights the need to find alternative approaches to current gonorrhea treatment such as vaccine development or novel therapeutics. The gonococcal OmpA protein was previously identified as a potential vaccine candidate due to its conservation and stable expression amongst strains of Neisseria gonorrhoeae. However, factors that might modulate levels of OmpA and therefore potential vaccine efficacy are unknown. Earlier work indicated that ompA is part of the MisR/MisS regulon and suggested that it was a MisR-activated gene. Herein, we confirmed MisR/MisS regulation of ompA and report that the MisR response regulator can bind upstream of the ompA translational start codon. Further, we describe the contribution of a DNA sequence upstream of the ompA promoter that is critical for MisR activation of ompA transcription. Our results provide a framework for understanding the transcription of gonococcal ompA through a regulatory system known to be important for survival of gonococci during experimental infection.
Highlights
The strict human pathogen Neisseria gonorrhoeae (Ng) is the etiologic agent of gonorrhea, which is the second most common sexually transmitted infection in the United States and causes an estimated 87 million infections globally per year[1,2]
Several surface-exposed, conserved and stably produced Ng antigens have been proposed as vaccine candidates; included in this list is a 23 kDa outer membrane protein termed OmpA that is similar to OmpA in other Gram-negative bacteria[9,10]
Evidence for transcriptional regulation of Ng ompA is suggested by results from two independent transcriptional profiling studies that included ompA as a gene that can be activated by the MisR/MisS sensory two-component regulatory system (TCS)[23,24]
Summary
The strict human pathogen Neisseria gonorrhoeae (Ng) is the etiologic agent of gonorrhea, which is the second most common sexually transmitted infection in the United States and causes an estimated 87 million infections globally per year[1,2]. We examined ompA transcript and protein levels in wild-type (WT) strain FA19, its isogenic misR-null mutant (JK100) and complemented strain (JK101) by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Results from qRT-PCR analysis showed that compared to their respective parental strain, the ompA transcript level was reduced in the MisR-negative mutant (Fig. 1b).
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