Pharmacodynamic activity of the lantibiotic MU1140.

This study evaluated the pharmacodynamics of the lantibiotic MU1140 and the ability of selected organisms to develop resistance to this antibiotic. MU1140 demonstrated activity against all Gram-positive organisms tested, including oxacillin- and vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis (VREF). No activity was observed against Gram-negative bacteria or yeast. Time-kill studies revealed that MU1140 was rapidly bactericidal against Streptococcus pneumoniae and multidrug-resistant S. aureus, whilst it was bacteriostatic against VREF. In vitro resistance development to MU1140, tested by sequential subculturing in subinhibitory concentrations of MU1140, revealed a stable threefold increase in the minimum inhibitory concentration (MIC) for S. aureus and S. pneumoniae. Subsequent subculturing of the strains with elevated MICs in antibiotic-free media for 7 days did not result in a reduction of their MIC values for MU1140. Collectively, our findings illustrate the therapeutic potential of MU1140 for management of Gram-positive infections.

Identification of in vivo-induced bacterial protein antigens during human infection with Salmonella enterica serovar Typhi.

We applied an immunoscreening technique, in vivo-induced antigen technology (IVIAT), to identify immunogenic bacterial proteins expressed during human infection with Salmonella enterica serovar Typhi, the cause of typhoid fever. We were able to assign a functional classification to 25 of 35 proteins identified by IVIAT. Of these 25, the majority represent proteins with known or potential roles in the pathogenesis of S. enterica. These include proteins implicated in fimbrial structure and biogenesis, antimicrobial resistance, heavy metal transport, bacterial adhesion, and extracytoplasmic substrate trafficking as well as secreted hydrolases. The 10 remaining antigens represent proteins with unknown functions. Of the 35 identified antigens, four had no immunoreactivity when probed with control sera from individuals never exposed to serovar Typhi organisms; these four included PagC, TcfB, and two antigens of unknown function encoded by STY0860 and STY3683. PagC is a virulence factor known to be upregulated in vivo in S. enterica serovar Typhimurium infection of mice. TcfB is the major structural subunit of a fimbrial operon found in serovar Typhi with no homolog in serovar Typhimurium organisms. By examining differential immunoreactivities in acute- versus convalescent-phase human serum samples, we found specific anti-PagC and anti-TcfB immunoglobulin G responses in patients with serovar Typhi bacteremia. Serovar Typhi antigens identified by IVIAT warrant further evaluation for their contributions to pathogenesis, and they may have diagnostic, therapeutic, or preventive uses.