Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male.

The opacity (Opa) proteins of Neisseria gonorrhoeae are a family of outer membrane proteins demonstrating phase and antigenic variation. N. gonorrhoeae strain FA0190 has 11 opa loci that encode at least 8 antigenically distinct Opa proteins. To determine if expression of one Opa protein or a subset of them is favored during gonococcal infection, we inoculated Opa-negative variants of strain FA1090 intraurethrally into male volunteers. The Opa phenotype of gonococci isolated from urine and urethral swab cultures from nine infected subjects was determined. Opa proteins were expressed in a large proportion of the reisolates from the infected subjects. Gonococci cultured from urine or urethral swab samples from six of the subjects were uniformly Opa positive, with the predominant Opa variants differing among subjects. Three different Opa proteins were represented as the predominant type in at least one subject each. In three subjects, there was more heterogeneity in Opa phenotype of the reisolates, including the presence of Opa-negative variants. An increase in the proportion of isolates expressing multiple Opa proteins occurred over time in most subjects. Passage of the inoculum in vitro did not result in similar changes in Opa expression. There was no detectable difference in infectivity of an Opa-negative variant and one expressing an Opa protein (OpaF) that was highly represented in reisolates from the original nine subjects. Reisolates from three infected volunteers inoculated with the OpaF variant showed continued expression of OpaF alone or in conjunction with other Opa proteins. These results demonstrate that there is strong selection for expression of one or more Opa proteins by strain FA1090 in vivo, but that no single protein is preferentially expressed during early infection in the male urethra.

Auditory pathways to the frontal cortex of the mustache bat, Pteronotus parnellii.

In primates, certain areas of the frontal cortex play a role in guiding movements toward visual or auditory objects in space. The projections from auditory centers to the frontal cortex of the bat Pteronotus parnellii were examined because echolocating bats utilize auditory cues to guide their movements in space. An area in the frontal cortex receives a direct projection from a division of the auditory thalamus, the suprageniculate nucleus, which in turn receives input from the anterolateral peri-olivary nucleus, an auditory center in the medulla. This pathway to the frontal cortex bypasses the main auditory centers in the midbrain and cortex and could involve as few as four neurons between the cochlea and the frontal cortex. The auditory cortex is also a major source of input to the frontal cortex. This area of the frontal cortex may link the auditory and motor systems by its projections to the superior colliculus.

Central acoustic tract in an echolocating bat: an extralemniscal auditory pathway to the thalamus.

To determine the sources and targets of auditory pathways that bypass the inferior colliculus in the mustache bat, we injected WGA-HRP in the medial geniculate body and related auditory nuclei of the thalamus as well as in the lower brainstem. We used electrophysiological methods to verify that the injection electrode was in an area responsive to sound. The only thalamic injections that produced retrograde transport to cells in auditory nuclei caudal to the inferior colliculus were those that included the suprageniculate nucleus. These injections labeled a group of large multipolar cells lying between the ventral nucleus of the lateral lemniscus and the superior olivary complex. Neurons in this cell group have also been shown to project to the deep layers of the superior colliculus in the mustache bat. The pathway revealed by these studies is almost identical to the "central acoustic tract" in which fibers course medial to the lateral lemniscus and bypass the inferior colliculus to reach the deep superior colliculus and the suprageniculate nucleus.

Human experimentation with Neisseria gonorrhoeae: rationale, methods, and implications for the biology of infection and vaccine development.

Neisseria gonorrhoeae infection is limited to the human host. Experimental urethral infection in male volunteers was used to study different aspects of the infection. Urethral installation of a variety of gonococcal variants (10(4)-10(6)) led to infection in 27 subjects, who developed pyuria and shed bacteria in urine before urethritis developed 1-6 days after gonococcal inoculation. The incubation period was affected by the inoculation procedure and size of the inoculum. Subjects were treated with intramuscular ceftriaxone (250 mg) if urethritis developed or at 6 days after inoculation. Urine cultures became negative within several hours of therapy, and symptoms resolved within 1 day of therapy. Infected patients suffered no major complications. Experimental male urethral gonococcal infection provides a unique opportunity to understand the biology and immunology of gonococcal infection and is an efficient method to test gonococcal vaccine candidates.

Characterisation of Neisseria gonorrhoeae in semen during urethral infection in men.

OBJECTIVE: To determine the number of Neisseria gonorrhoeae organisms in urine and semen in men with gonococcal urethritis, and to compare selected phenotypic characteristics of organisms harvested from the urethra and semen. DESIGN: Samples from two groups of subjects were examined. Patients with symptomatic urethritis receiving treatment at an STD clinic, as well as six subjects with experimental urethritis. Semen and urine specimens were obtained after the urethral exudate was sampled. RESULTS: Using quantitative cultures, we found an average of 6 x 10(6) gonococci in urine or semen of 17 men with symptomatic urethritis seeking treatment at an STD clinic, and 2 x 10(4) gonococci in secretions of six male subjects with early experimental infection. Gonococcal outer membrane opacity (Opa) proteins and lipo-oligosaccharide (LOS) recovered from urine and semen of these subjects were very similar. CONCLUSIONS: Men with symptomatic gonorrhoea excrete a large number of gonococci in semen which is not affected by the duration of symptoms. The similar phenotype of organisms in urine and semen suggests the bacteria come from the same compartment. These data help to explain the efficiency of gonococcal transmission from men to their partners, and identify an appropriate target for a preventative vaccine or immunotherapy designed to reduce the inoculum in infected patients.

Time required for elimination of Neisseria gonorrhoeae from the urogenital tract in men with symptomatic urethritis: comparison of oral and intramuscular single-dose therapy.

BACKGROUND AND OBJECTIVES: The spread of sexually transmitted diseases (STDs), including gonorrhea, is affected by the duration of infection. Oral antibiotic therapy for gonococcal infection has been shown to be as effective as conventional intramuscular injection with ceftriaxone. Rapid cure would be expected to limit further spread of gonorrhea. However, the speed with which Neisseria gonorrhoeae is eliminated from the urogenital tract has not been evaluated. GOAL OF THIS STUDY: To determine the time required for elimination of Neisseria gonorrhoeae for the urine, mucosa, and semen in male subjects after treatment with ceftriaxone (250 mg intramuscularly), ciprofloxacin (500 mg by mouth, single dose) or cefixime (400 mg by mouth, single dose.) RESULTS: In 14 subjects, gonococci were eliminated from the urine within 4 hours of therapy and the mucosa within 24 hours after therapy. In 9 additional subjects, gonococci were eliminated from the semen by 24 hours after therapy. CONCLUSIONS: These results support the efficacy of single-dose oral therapy for gonorrhea and suggest that earlier follow-up for proof of cure in clinical trials of new antibiotics for gonorrhea may be acceptable. Rapid elimination of gonorrhea reduces the risk for continued transmission of the organism.