Behçetʼs disease complicated by ileocecal and esophageal perforation

　A 36-year-old Japanese man known to have incomplete Behçet’s disease (oral aphthous ulcers, genital ulcers, skin lesions, and esophageal and ileocecal ulcers) was admitted to our hospital in January 2011 for abdominal pain. We administered corticosteroids and immunosuppressants. Two months later, we performed an ileocecal resection to control gastrointestinal bleeding from the ileocecal ulcers. High fever persisted after this surgery, and upper gastrointestinal endoscopy demonstrated ulcer penetration between the lower and abdominal esophagus. Eighteen days after the initial ileocecal resection, we performed a lower esophagus resection, gastric tube reconstruction and enterostomy, during which we confirmed a 5-mm-dia. perforated site at the posterior wall of the abdominal esophagus. Postoperative anastomotic leakage and empyema occurred, but they were relieved by thoracic drainage and empyema dissection

Knockout of mlaA increases Escherichia coli virulence in a silkworm infection model

The mlaA gene encodes a lipoprotein to maintain an outer membrane lipid asymmetry in gram-negative bacteria. Although the role of mlaA in bacterial virulence has been studied in several bacterial species, there are no reports of its role in E. coli virulence. In this study, we found that knockout of mlaA in E. coli increased its virulence against silkworms. The mlaA-knockout mutant was sensitive to several antibiotics and detergents, but resistant to vancomycin and chlorhexidine. The mlaA-knockout mutant grew faster than the parent strain in the presence of silkworm hemolymph. The mlaA-knockout mutant also produced a larger amount of outer membrane vesicles than the parent strain. These findings suggest that mlaA knockout causes E. coli resistance to specific antimicrobial substances and increases outer membrane vesicle production, thereby enhancing E. coli virulence properties in the silkworm infection model

Knockout of mlaA increases Escherichia coli virulence in a silkworm infection model.

The mlaA gene encodes a lipoprotein to maintain an outer membrane lipid asymmetry in gram-negative bacteria. Although the role of mlaA in bacterial virulence has been studied in several bacterial species, there are no reports of its role in E. coli virulence. In this study, we found that knockout of mlaA in E. coli increased its virulence against silkworms. The mlaA-knockout mutant was sensitive to several antibiotics and detergents, but resistant to vancomycin and chlorhexidine. The mlaA-knockout mutant grew faster than the parent strain in the presence of silkworm hemolymph. The mlaA-knockout mutant also produced a larger amount of outer membrane vesicles than the parent strain. These findings suggest that mlaA knockout causes E. coli resistance to specific antimicrobial substances and increases outer membrane vesicle production, thereby enhancing E. coli virulence properties in the silkworm infection model

Knockout of ribosomal protein RpmJ leads to zinc resistance in Escherichia coli.

Zinc is an essential metal for cells, but excess amounts are toxic. Other than by regulating the intracellular zinc concentration by zinc uptake or efflux, the mechanisms underlying bacterial resistance to excess zinc are unknown. In the present study, we searched for zinc-resistant mutant strains from the Keio collection, a gene knockout library of Escherichia coli, a model gram-negative bacteria. We found that knockout mutant of RpmJ (L36), a 50S ribosomal protein, exhibited zinc resistance. The rpmJ mutant was sensitive to protein synthesis inhibitors and had altered translation fidelity, indicating ribosomal dysfunction. In the rpmJ mutant, the intracellular zinc concentration was decreased under excess zinc conditions. Knockout of ZntA, a zinc efflux pump, abolished the zinc-resistant phenotype of the rpmJ mutant. RNA sequence analysis revealed that the rpmJ mutant exhibited altered gene expression of diverse functional categories, including translation, energy metabolism, and stress response. These findings suggest that knocking out RpmJ alters gene expression patterns and causes zinc resistance by lowering the intracellular zinc concentration. Knockouts of other ribosomal proteins, including RplA, RpmE, RpmI, and RpsT, also led to a zinc-resistant phenotype, suggesting that deletion of ribosomal proteins is closely related to zinc resistance

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028)

This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12–15 months of age. Diphtheria, tetanus, and pertussis–inactivated poliovirus (DTaP–IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP–IPV at 1-month post-dose 3 (PD3). On days 1–14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP–IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic