Disseminated Gonococcal Infection

Holmes, King K.; Counts, George W.; Beaty, Harry N.

doi:10.7326/0003-4819-74-6-979

Cited by 363 publications

(121 citation statements)

References 75 publications

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“…4). The only other specific contact is a van der Waals interaction between the side chain of Val 5 and the thymine from the T/A sequence central to each inverted repeat (Fig. 4a).…”

Section: Resultsmentioning

confidence: 99%

“…3, a and b). The ␤1-strands from each FitA monomer combine to form a two stranded antiparallel ␤-sheet with four intersubunit hydrogen bonds between the backbone carbonyl oxygen and amide nitrogen atoms and a van der Waals contact between the side chains of Val 5 and its dyadic mate (Fig. 3a).…”

Section: Resultsmentioning

confidence: 99%

“…The immune response to bacteria in the subepithelium produces the inflammation and purulent discharge characteristic of gonorrhea (4,5). On occasion, GC establish a carrier state in which an asymptomatic individual harbors culturable and transmissible bacteria.…”

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confidence: 99%

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Structure of FitAB from Neisseria gonorrhoeae Bound to DNA Reveals a Tetramer of Toxin-Antitoxin Heterodimers Containing Pin Domains and Ribbon-Helix-Helix Motifs

Mattison

Wilbur

et al. 2006

Journal of Biological Chemistry

119

160

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Neisseria gonorrhoeae is a sexually transmitted pathogen that initiates infections in humans by adhering to the mucosal epithelium of the urogenital tract. The bacterium then enters the apical region of the cell and traffics across the cell to exit into the subepithelial matrix. Mutations in the fast intracellular trafficking (fitAB) locus cause the bacteria to transit a polarized epithelial monolayer more quickly than the wild-type parent and to replicate within cells at an accelerated rate. Here, we describe the crystal structure of the toxin-antitoxin heterodimer, FitAB, bound to a high affinity 36-bp DNA fragment from the fitAB promoter. FitA, the antitoxin, binds DNA through its ribbonhelix-helix motif and is tethered to FitB, the toxin, to form a heterodimer by the insertion of a four turn ␣-helix into an extensive FitB hydrophobic pocket. Neisseria gonorrhoeae (GC) 3 is the agent of the sexually transmitted disease, gonorrhea. The mechanisms used by GC to initiate infection have been very well characterized. Gonococci adhere via a multistep cascade and subsequently enter cells forming the epithelial barrier of the urogenital tract, traffic across these cells and exit into the subepithelial matrix (1, 2). Although studies have identified many of the molecular mechanisms used by GC to adhere to and enter cells, our knowledge of the mechanisms that operate in the later stages of infection is limited.GC are able to survive and grow within epithelial cells (3); they also traverse the epithelial monolayer to infect the stromal tissue of the subepithelium (2). The immune response to bacteria in the subepithelium produces the inflammation and purulent discharge characteristic of gonorrhea (4, 5). On occasion, GC establish a carrier state in which an asymptomatic individual harbors culturable and transmissible bacteria. These carriers are key to the spread of gonococcal disease, as humans are the only known reservoir for GC (6). The mechanisms by which GC maintains this persistent state are unknown. One hypothesis is that the organism resides within the epithelial cells instead of crossing into the subepithelium, thus evading the host immune response. The gene product(s) that affect GC intracellular growth and transcytosis are therefore important for the maintenance of gonococci in the human population.The fitAB operon was identified in a screen for GC mutants with a fast intracellular trafficking phenotype across polarized epithelial monolayers (3). A GC mutant that lacks fitAB grows normally extracellularly, but has an accelerated rate of intracellular replication with a concomitant increase in the rate at which this mutant traverses a monolayer of polarized epithelial cells. Thus, either FitA or FitB, or their complex, is hypothesized to slow intracellular replication and intracellular trafficking of GC.FitA is an 8.4-kDa protein with a predicted N-terminal ribbon-helix-helix (RHH) DNA binding motif (7,8). FitB is a 15.3-kDa protein with a predicted PIN (PilT-N terminus) domain according to the BLAST search t...

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“…4). The only other specific contact is a van der Waals interaction between the side chain of Val 5 and the thymine from the T/A sequence central to each inverted repeat (Fig. 4a).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Structure of FitAB from Neisseria gonorrhoeae Bound to DNA Reveals a Tetramer of Toxin-Antitoxin Heterodimers Containing Pin Domains and Ribbon-Helix-Helix Motifs

Mattison

Wilbur

et al. 2006

Journal of Biological Chemistry

119

160

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“…Since the advent of effective antimicrobial therapy, however, drainage by needle aspiration has also been used successfully in treating many patients with acute bacterial joint infection (7,1617). Today, there is general agreement that most cases of gonococcal arthritis respond well to antibiotic therapy without surgical drainage (18)(19)(20). Still, because of fear that closed aspiration will fail to provide adequate drainage for nongonococcal joint infections, many physicians continue to rely empirically upon surgery, either initially or at a very early stage (2122).…”

Section: Discussionmentioning

confidence: 99%

Treatment of septic arthritis

Goldenberg

Brandt

Cohen

et al. 1975

Arthritis & Rheumatism

194

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Surgery and needle aspiration have been evaluated as initial modes of drainage in 59 patients with acute septic arthritis. Full recovery was noted in 42y0 treated surgically at the outset. On the other hand, 67% of those treated by needle aspiration recovered without sequelae, despite the greater prevalence in this group of adverse host factors-eg, serious underlying From the Arthritis and Connective Tissue Disease Section,

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“…This is in sharp contrast to the experience in the Western urban medical centers where gonococcus is the most common cause of bacterial arthritis. 9,[22][23][24] Since our laboratory procedure is adequate to identify the gonococcus, this observation may be due to the religious, social and cultural teachings in this country that prohibit extramarital sex.…”

Section: Discussionmentioning

confidence: 99%

Nongonococcal Septic Arthritis at a Major Teaching Hospital in Riyadh, Saudi Arabia

Al-Ballaa

1995

Ann Saudi Med

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Twenty five (25) consecutive cases of nongonococcal septic arthritis admitted to King Khalid University Hospital were retrospectively reviewed. The patients were mostly adults (64%) and Staphylococcus aureus was the most common bacterial species isolated (69%). Predisposing factors were identified in 52% of patients, including diabetes mellitus in seven patients, pre-existing joint disease in two patients and the infection followed intraarticular steroid injections in two patients. All patients were treated with appropriate antibiotics; however, 11 (44%) patients were left with permanent joint damage.

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Disseminated Gonococcal Infection

Cited by 363 publications

References 75 publications

Structure of FitAB from Neisseria gonorrhoeae Bound to DNA Reveals a Tetramer of Toxin-Antitoxin Heterodimers Containing Pin Domains and Ribbon-Helix-Helix Motifs

Structure of FitAB from Neisseria gonorrhoeae Bound to DNA Reveals a Tetramer of Toxin-Antitoxin Heterodimers Containing Pin Domains and Ribbon-Helix-Helix Motifs

Treatment of septic arthritis

Nongonococcal Septic Arthritis at a Major Teaching Hospital in Riyadh, Saudi Arabia

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