Toshiki Maruyama

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.

Constrained molecular dynamics approach to fermionic systems

We propose a Constraint Molecular Dynamics model for Fermionic system. In this approach the equations of motion of wave packets for the nuclear many-body problem are solved by imposing that the one-body occupation probability

Quantum molecular dynamics approach to the nuclear matter below the saturation density

\bar{f}(r,p,t)

Nuclear “pasta” structures and the charge screening effect

can assume only values less or equal to 1. This condition reflects the Fermionic nature of the studied systems and it is implemented with a fast algorithm which allows also the study of the heaviest colliding system. The parameters of the model have been chosen to reproduce the average binding energy and radii of nuclei in the mass region

Extension of quantum molecular dynamics and its application to heavy-ion collisions

A=30\sim 208

Nucleon flow and fragment flow in heavy ion reactions

. Some comparison to data is given.

Momentum distribution of fragments in heavy-ion reactions: Dependence on the stochastic collision process.

Quantum molecular dynamics is applied to study the ground state properties of nuclear matter at subsaturation densities. Clustering effects are observed as to soften the equation of state at these densities. The structure of nuclear matter at subsaturation density shows some exotic shapes with variation of the density.

Relativistic Effects in Transverse Flow in the Molecular Dynamics Framework

Nonuniform structures of the nucleon matter at subnuclear densities are numerically studied by means of the density functional theory with relativistic mean fields coupled with the electric field. A particular role of the charge screening effects is demonstrated.

Numerical study of the hadron-quark mixed phase

In order to treat low-energy heavy-ion reactions, we make an extension of quantum molecular dynamics method. A phenomenological Pauli potential is introduced into effective interactions to approximate the nature of the Fermion many-body system. We treat the widths of nucleon wave-packets as time-dependent dynamical variables. With these modifications, our model can well describe the ground-state properties in wide mass range. Improvements due to the extension are also obtained in the nucleus-nucleus collision calculations.

Nuclear Level Structure, B(E2) Gamma-transitions and Nucleon Interaction Data for 56Fe by a Unified Soft-rotator Model and Coupled-Channels Framework

The collective flow of nucleons and that of fragments in the [sup 12]C+[sup 12]C reaction below 150 MeV/nucleon are calculated with the antisymmetrized version of molecular dynamics combined with the statistical decay calculation. The density dependent Gogny force is used as the effective interaction. The calculated balance energy is about 100 MeV/nucleon, which is close to the observed value. Below the balance energy, the absolute value of the fragment flow is larger than that of nucleon flow, which is also in accordance with data. The dependence of the flow on the stochastic collision cross section and its origin are discussed. All the results are naturally understood by introducing the concept of two components of flow: the flow of dynamically emitted nucleons and the flow of the nuclear matter which contributes to both the flow of fragments and the flow of nucleons due to the statistical decay.