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A series of 12 Staphylococcus aureus strains of various genetic backgrounds, methicillin resistance levels, and autolytic activities were subjected to selection for the glycopeptide-intermediate S. aureus (GISA) susceptibility phenotype on increasing concentrations of vancomycin. Six strains acquired the phenotype rapidly, two did so slowly, and four failed to do so. The vancomycin MICs for the GISA strains ranged from 4 to 16 g/ml, were stable to 20 nonselective passages, and expressed resistance homogeneously. Neither ease of acquisition of the GISA phenotype nor the MIC attained correlated with methicillin resistance hetero-versus homogeneity or autolytic deficiency or sufficiency. Oxacillin MICs were generally unchanged between parent and GISA strains, although the mec members of both isogenic methicillin-susceptible and methicillin-resistant pairs acquired the GISA phenotype more rapidly and to higher MICs than did their susceptible counterparts. Transmission electron microscopy revealed that the GISA strains appeared normal in the absence of vancomycin but had thickened and diffuse cell walls when grown with vancomycin at one-half the MIC. Common features among GISAs were reduced doubling times, decreased lysostaphin susceptibilities, and reduced whole-cell and zymographic autolytic activities in the absence of vancomycin. This, with surface hydrophobicity differences, indicated that even in the absence of vancomycin the GISA cell walls differed from those of the parents. Autolytic activities were further reduced by the inclusion of vancomycin in whole-cell and zymographic studies. The six least vancomycin-susceptible GISA strains exhibited an increased capacity to remove vancomycin from the medium versus their parent lines. This study suggests that while some elements of the GISA phenotype are strain specific, many are common to the phenotype although their expression is influenced by genetic background. GISA strains with similar glycopeptide MICs may express individual components of the phenotype to different extents.

Exhumation of the southern Tibetan plateau margin reflects interplay between surface and lithospheric dynamics within the Himalaya-Tibet orogen. We report thermochronometric data from a 1.2-km elevation transect within granitoids of the eastern Lhasa terrane, southern Tibet, which indicate rapid exhumation exceeding 1 km/Ma from 17-16 to 12-11 Ma followed by very slow exhumation to the present. We hypothesize that these changes in exhumation occurred in response to changes in the loci and rate of rock uplift and the resulting southward shift of the main topographic and drainage divides from within the Lhasa terrane to their current positions within the Himalaya. At ∼17 Ma, steep erosive drainage networks would have flowed across the Himalaya and greater amounts of moisture would have advected into the Lhasa terrane to drive large-scale erosional exhumation. As convergence thickened and widened the Himalaya, the orographic barrier to precipitation in southern Tibet terrane would have strengthened. Previously documented midcrustal duplexing around 10 Ma generated a zone of high rock uplift within the Himalaya. We use numerical simulations as a conceptual tool to highlight how a zone of high rock uplift could have defeated transverse drainage networks, resulting in substantial drainage reorganization. When combined with a strengthening orographic barrier to precipitation, this drainage reorganization would have driven the sharp reduction in exhumation rate we observe in southern Tibet.Tibet-Himalaya | thermochronometry | landscape evolution T he Himalaya-Tibet orogenic system, formed by collision between India and Asia beginning ca. 50 Ma, is the most salient topographic feature on Earth and is considered the archetype for understanding continental collision. Geophysical and geologic research has illuminated the modern structure and dynamics of the orogen (1). Nonetheless, how the relatively low relief and high elevation Tibetan plateau grew spatially and temporally and what underlying mechanism(s) drove the patterns of plateau growth remain outstanding questions.In the internally drained central Tibetan plateau, evidence from carbonate stable isotopes suggest that high elevations persisted since at least 25-35 Ma (2, 3). Sustained high elevations since shortly after collision commenced have also been used to explain low long-term erosion rates in the internally drained plateau interior (4-6). In contrast to the central plateau, the externally drained Tibetan plateau margins serve as the headwaters for many major river systems in Asia. Because externally drained rivers provide an erosive mechanism to destroy uplifted terrane, understanding why these rivers have not incised further and more deeply into the Tibetan plateau is essential to decipher how the plateau grew. Recent research in the eastern (7, 8) and northern (9) Tibetan plateau indicates that erosion rates have increased significantly since ∼10 Ma. These increases suggest that rock uplift rates have also increased and that the plateau has expanded to the e...

The microdilution plating method, using colony-forming units (CFU)/ml determinations from 10-microl droplets, was compared with the standard plate count in population analyses of methicillin-resistant and glycopeptide-intermediate Staphylococcus aureus (MRSA and GISA) strains. Efficiency of plating plots yielded similar population resistance profiles for both methods with MRSA class 1-4 strains, laboratory-selected GISA strains of varying susceptibilities, two clinical GISA strains, as well as susceptible strains. A single heterogeneous MRSA, plated by both methods in 41 trials with and without 50 microg/ml oxacillin present, demonstrated no significant difference between the results of the two methods of colony counting (p > 0.05, and r = 0.67). Standard plating and microdilution plating produced mean resistant subpopulation determinations of one cell in 1.19 x 10(4) and 1.36 x 10(4), respectively. Population analyses carried out by microdilution plating require one-fourth or fewer of the plates used for standard plating, and both plating and colony counting required less time to perform.

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