Bacterial vaginosis-associated bacteria in men: association of Leptotrichia/Sneathia spp. with nongonococcal urethritis.

BACKGROUND: Approximately 45% of nongonococcal urethritis cases have no identified etiology. Novel bacteria recently associated with bacterial vaginosis (BV) in women may be involved. We evaluated the association of idiopathic nongonococcal urethritis and 5 newly described BV-associated bacteria (BVAB). METHODS: Heterosexual men 16 years or older attending a sexually transmitted disease clinic in Seattle, Washington, from May 2007 to July 2011 and negative for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, and Ureaplasma urealyticum-biovar2 were eligible. Cases had urethral discharge or 5 or more polymorphonuclear leukocytes per high-power field in urethral exudates. Controls had no urethral discharge and less than 5 polymorphonuclear leukocytes per high-power field. Urine was tested for Atopobium spp., BVAB-2, BVAB-3, Megasphaera spp., and Leptotrichia/Sneathia spp. using quantitative taxon-directed polymerase chain reaction. RESULTS: Cases (n = 157) and controls (n = 102) were of similar age, education, and income, and most were white. Leptotrichia/Sneathia spp. was significantly associated with urethritis (24/157 [15.3%] vs. 6/102 [5.9%], P = 0.03). BVAB-2 was more common in cases than in controls (7/157 [4.5%] vs. 1/102 [1.0%], P = 0.15), and BVAB-3 (n = 2) and Megasphaera spp. (n = 1) were only detected in men with urethritis, but these bacteria were found only in men who also had Leptotrichia/Sneathia spp. Atopobium spp. was not associated with urethritis. The quantity of bacteria did not differ between cases and controls. Among treated cases, doxycycline was more effective than azithromycin for clinical cure of men with Leptotrichia/Sneathia spp. (9/10 vs. 7/12, P = 0.16) and BVAB-2 (3/3 vs. 0/3, P = 0.10). CONCLUSIONS: Leptotrichia/Sneathia spp. may be urethral pathogens or contribute to a pathogenic microbiota that can also include BVAB-2, BVAB-3, and Megasphaera spp. Doxycycline may be more effective than azithromycin against these newly identified bacteria.

Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm.

BACKGROUND: We investigated the roles of p120 catenin, Cdc42, Rac1, and RhoA GTPases in regulating migration of presomitic mesoderm cells in zebrafish embryos. p120 catenin has dual roles: It binds the intracellular and juxtamembrane region of cadherins to stabilize cadherin-mediated adhesion with the aid of RhoA GTPase, and it activates Cdc42 GTPase and Rac1 GTPase in the cytosol to initiate cell motility. RESULTS: During gastrulation of zebrafish embryos, knockdown of the synthesis of zygotic p120 catenin δ1 mRNAs with a splice-site morpholino caused lateral widening and anterior-posterior shortening of the presomitic mesoderm and somites and a shortened anterior-posterior axis. These phenotypes indicate a cell-migration effect. Co-injection of low amounts of wild-type Cdc42 or wild-type Rac1 or dominant-negative RhoA mRNAs, but not constitutively-active Cdc42 mRNA, rescued these p120 catenin δ1-depleted embryos. CONCLUSIONS: These downstream small GTPases require appropriate spatiotemporal stimulation or cycling of GTP to guide mesodermal cell migration. A delicate balance of Rho GTPases and p120 catenin underlies normal development.