Intracellular pathogenic organisms such as salmonellae and shigellae are able to evade the effects of many antibiotics because the drugs are not able to penetrate the plasma membrane. In addition, these bacteria may be able to transfer genes within cells while protected from the action of drugs. The primary mode by which virulence and antibiotic resistance genes are spread is bacterial conjugation. Salmonellae have been shown to be competent for conjugation in the vacuoles of cultured mammalian cells. We now show that the conjugation machinery is also functional in the mammalian cytosol. Specially constructed Escherichia coli strains expressing Shigella flexneri plasmid and chromosomal virulence factors for escape from vacuoles and synthesizing the invasin protein from Yersinia pseudotuberculosis to enhance cellular entry were able to enter 3T3 cells and escape from the phagocytic vacuole. One bacterial strain (the donor) of each pair to be introduced sequentially into mammalian cells had a conjugative plasmid. We found that this plasmid could be transferred at high frequency. Conjugation in the cytoplasm of cells may well be a general phenomenon.

Background and Aims: Chronic Hepatitis B (CHB) and C (CHC) lead to chronic liver disease and complications if left untreated. Our study was to evaluate antiviral therapy for both CHB and CHC on clinical outcomes and liver related complications.Methods: Eighty-three CHB and twenty-one CHC patients were included. Inclusion criteria were HBVDNA>10 5 copies/ml, abnormal Liver Function Tests (LFTs), cirrhosis and positive HCVRNA. Daily Lamivudine with/without Adefovir rescue therapy and Pegylated Interferon with Ribavirin were prescribed. Exclusion criteria were hepatocellular carcinoma, renal failure, and CHB/CHC/HIV co-infection. Outcomes measured were: proportion of patients who i) normalize LFTs, ii) achieve sustained virological remission, iii) improve Child-Pugh (CP) score, iv) develop liver related complications and v) die.Results: CHB: Thirty-one patients (37%) had baseline cirrhosis. The mean therapy duration was 67.5 months. At the end of study, 100% had undetectable HBVDNA and 98% had LFTs normalization. The majority (87%) had stable C-P score, of whom 11.42% had improvement of score >2 points. Lamivudine resistance developed in 59.5% requiring add-on Adefovir therapy. Only eleven patients (13%) developed complications. CHC: There were 21 patients (genotype1=62%). Eight patients (38%) had baseline cirrhosis. LFTs improved in 18 patients (86%). The overall end-of-treatment response and SVR were 95% and 86% while SVR for genotype 1 and 2/3 were 92% and 75% respectively. No major liver related complications or mortality were noted.Conclusion: Antiviral therapy resulted in excellent clinical outcomes with disease complication free in 87% of CHB and 100% of CHC patients.