Rothia aeria and Rothia dentocariosa as biofilm builders in infective endocarditis.

BACKGROUND: Rothia sp. are Gram-positive bacteria in the class of Actinobacteria that are part of the physiological oral flora. In rare cases, Rothia aeria and Rothia dentocariosa can cause infective endocarditis (IE). The biofilm potential of Rothia in endocarditis is unknown. METHODS: Specimen from two cases of Rothia endocarditis were obtained during cardiac surgery. One of the patients suffered mitral valve IE from Rothia aeria. In the other case, IE of a prosthetic pulmonary valve was caused by Rothia dentocariosa. Fluorescence in situ hybridization (FISH) was used for visualization of microorganisms within heart valve tissues in combination with PCR and sequencing (FISHseq). RESULTS: The two heart valve specimens featured mature biofilms of bacteria that were identified by FISHseq as Rothia aeria and Rothia dentocariosa, respectively. FISH showed in situ biofilms of both microorganisms that feature distinct phenotypes for the first time ex vivo. Both of our reported cases were treated successfully by heart valve surgery and antibiotic therapy using beta-lactam antibiotics. CONCLUSION: The biofilm potential of Rothia sp. must be taken into account. The awareness of Rothia aeria and Rothia dentocariosa as rare but relevant pathogens for infective endocarditis must be raised. Use of biofilm-effective antibiotics in Rothia IE should be discussed.

Minocycline inhibits West Nile virus replication and apoptosis in human neuronal cells.

OBJECTIVES: West Nile virus (WNV) infection causes severe meningitis and encephalitis in a subset of patients. WNV-induced apoptosis has been suggested to contribute to WNV pathogenesis. Tetracyclines exert antiviral effects against HIV and inhibit apoptosis in different models of neuronal disease. Here, the effects of the tetracyclines minocycline, demeclocycline and chlortetracycline were observed on WNV replication and WNV-induced apoptosis in different human CNS-derived cell types (primary human brain neurons, primary human retinal pigment epithelial cells and T98G human glioma cell line). METHODS: WNV replication was studied by cytopathic effects and virus yield reduction assay. Cell viability was examined by MTT assay. Apoptosis was investigated by immunostaining for activated caspase 3 and cleaved poly(ADP-ribose) polymerase. Expression and phosphorylation of cellular proteins were examined by western blot. RESULTS: Minocycline exerted the strongest anti-WNV activity. Non-toxic minocycline concentrations that can be achieved in human tissues significantly reduced WNV titres in all cell types tested. Minocycline inhibited WNV-induced apoptosis and suppressed virus-induced activation of c-Jun N-terminal kinase (JNK) and its target c-jun. The JNK inhibitor L-JNKi exerted similar effects to minocycline. CONCLUSIONS: These data suggest that minocycline-induced inhibition of JNK activation contributes to minocycline-induced inhibition of WNV replication and WNV-induced apoptosis. Minocycline is a clinically available, inexpensive and generally very well-tolerated drug. It could be readily evaluated for the treatment of humans with serious WNV infection.