Yataro Horikawa

Novel Mechanism of Antibiotic Resistance Originating in Vancomycin-Intermediate Staphylococcus aureus

ABSTRACT As an aggressive pathogen, Staphylococcus aureus poses a significant public health threat and is becoming increasingly resistant to currently available antibiotics, including vancomycin, the drug of last resort for gram-positive bacterial infections. S. aureus with intermediate levels of resistance to vancomycin (vancomycin-intermediate S. aureus [VISA]) was first identified in 1996. The resistance mechanism of VISA, however, has not yet been clarified. We have previously shown that cell wall thickening is a common feature of VISA, and we have proposed that a thickened cell wall is a phenotypic determinant for vancomycin resistance in VISA (L. Cui, X. Ma, K. Sato, et al., J. Clin. Microbiol. 41:5-14, 2003). Here we show the occurrence of an anomalous diffusion of vancomycin through the VISA cell wall, which is caused by clogging of the cell wall with vancomycin itself. A series of experiments demonstrates that the thickened cell wall of VISA could protect ongoing peptidoglycan biosynthesis in the cytoplasmic membrane from vancomycin inhibition, allowing the cells to continue producing nascent cell wall peptidoglycan and thus making the cells resistant to vancomycin. We conclude that the cooperative effect of the clogging and cell wall thickening enables VISA to prevent vancomycin from reaching its true target in the cytoplasmic membrane, exhibiting a new class of antibiotic resistance in gram-positive pathogens.

Polarization effects for higher multipoles

Abstract First order polarization effects on E2, E4, E6, M3, M5, and M7 multipoles are calculated for the 16 O and 40 Ca cores and the multipole dependence of the polarization charges are investigated. It is concluded that such large negative E6 polarization charges as required in recent analyses can not be ascribed to the core polarization effects.

Meson exchange effects on the deuteron magnetic moment

Abstract Meson exchange correction to the deuteron magnetic moment is investigated by dividing it into the long range and the short range parts. The former is related to the pion-photo-production amplitude for which the ϱ -meson exchange model is used, but its reliable estimation is difficult at present. The latter is calculated within the framework of the one-boson-exchange model which describes two-nucleon data quite well. It is found that the short range part is sufficient to explain the observed value of the deuteron magnetic moment.

Relativistic Hartree approach with exact treatment of vacuum polarization for finite nuclei

We study the relativistic Hartree approach with an exact treatment of the vacuum polarization in the Walecka

Nuclear polarization in hydrogenlike 82 208 Pb 8 1

(\ensuremath{\sigma}\text{\ensuremath{-}}\ensuremath{\omega})

Transverse nuclear polarization in muonic 208Pb

model. The contribution from the vacuum polarization of the nucleon-antinucleon field to the source term of the meson fields is evaluated by performing the energy integrals of the Dirac Green function along the imaginary axis. With the present method of calculating the vacuum polarization in finite system, the total binding energies and charge radii of

Self-consistent relativistic random-phase approximation with vacuum polarization

^{16}\mathrm{O}

Gauge invariant evaluation of nuclear polarization with the collective model

and

Energy-dependent anisotropy of beta-rays and second-class currents

^{40}\mathrm{Ca}

NUCLEAR GROUND STATES AND EXCITATIONS IN RELATIVISTIC NUCLEAR MODELS

can be reproduced. On the other hand, the level splittings in the single-particle level, in particular the spin-orbit splittings, are not described well because the inclusion of vacuum effect provides a large effective mass with small meson fields. We also show that the derivative expansion of the effective action is fairly useful for the estimation of the vacuum effect.