Alternative evolutionary paths to bacterial antibiotic resistance cause distinct collateral effects.

Published onlineJournal ArticleThis is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record.When bacteria evolve resistance against a particular antibiotic, they may simultaneously gain increased sensitivity against a second one. Such collateral sensitivity may be exploited to develop novel, sustainable antibiotic treatment strategies aimed at containing the current, dramatic spread of drug resistance. To date, the presence and molecular basis of collateral sensitivity has only been studied in few bacterial species and is unknown for opportunistic human pathogens such as Pseudomonas aeruginosa. In the present study, we assessed patterns of collateral effects by experimentally evolving 160 independent populations of P. aeruginosa to high levels of resistance against eight commonly used antibiotics. The bacteria evolved resistance rapidly and expressed both collateral sensitivity and cross-resistance. The pattern of such collateral effects differed to those previously reported for other bacterial species, suggesting inter-specific differences in the underlying evolutionary trade-offs. Intriguingly, we also identified contrasting patterns of collateral sensitivity and cross-resistance among the replicate populations adapted to the same drug. Whole-genome sequencing of 81 independently evolved populations revealed distinct evolutionary paths of resistance to the selective drug, which determined whether bacteria became cross-resistant or collaterally sensitive towards others. Based on genomic and functional genetic analysis, we demonstrate that collateral sensitivity can result from resistance mutations in regulatory genes such as nalC or mexZ, which mediate aminoglycoside sensitivity in β-lactam-adapted populations, or the two-component regulatory system gene pmrB, which enhances penicillin sensitivity in gentamicin-resistant populations. Our findings highlight substantial variation in the evolved collateral effects among replicates, which in turn determine their potential in antibiotic therapy.We thank Anette Friedrichs, Lutz Becks, and the Schulenburg group for valuable advice and Melanie Vollstedt for technical support during genome sequencing. We are grateful for financial support from the German Science Foundation (DFG grant SCHU 1415/12-1) and the International Max-Planck Research School for Evolutionary Biology at the University of Kiel. We acknowledge infrastructural support by the DFG excellence cluster Inflammation at Interfaces

Relativistic Aharonov-Casher Phase in Spin One

The Aharonov-Casher (AC) phase is calculated in relativistic wave equations of spin one. The AC phase has previously been calculated from the Dirac-Pauli equation using a gauge-like technique \cite{MK1,MK2}. In the spin-one case, we use Kemmer theory (a Dirac-like particle theory) to calculate the phase in a similar manner. However the vector formalism, the Proca theory, is more widely known and used. In the presence of an electromagnetic field, the two theories are `equivalent' and may be transformed into one another. We adapt these transformations to show that the Kemmer theory results apply to the Proca theory. Then we calculate the Aharonov-Casher phase for spin-one particles directly in the Proca formalism.Comment: 12 page

Comment on ``the Klein-Gordon Oscillator''

The different ways of description of the $S=0$ particle with oscillator-like interaction are considered. The results are in conformity with the previous paper of S. Bruce and P. Minning.Comment: LaTeX file, 5p

Status of a DEPFET pixel system for the ILC vertex detector

We have developed a prototype system for the ILC vertex detector based on DEPFET pixels. The system operates a 128x64 matrix (with ~35x25 square micron large pixels) and uses two dedicated microchips, the SWITCHER II chip for matrix steering and the CURO II chip for readout. The system development has been driven by the final ILC requirements which above all demand a detector thinned to 50 micron and a row wise read out with line rates of 20MHz and more. The targeted noise performance for the DEPFET technology is in the range of ENC=100 e-. The functionality of the system has been demonstrated using different radioactive sources in an energy range from 6 to 40keV. In recent test beam experiments using 6GeV electrons, a signal-to-noise ratio of S/N~120 has been achieved with present sensors being 450 micron thick. For improved DEPFET systems using 50 micron thin sensors in future, a signal-to-noise of 40 is expected.Comment: Invited poster at the International Symposium on the Development of Detectors for Particle, AstroParticle and Synchrotron Radiation Experiments, Stanford CA (SNIC06) 6 pages, 12 eps figure

Exact Solution of Photon Equation in Stationary G\"{o}del-type and G\"{o}del Space-Times

In this work the photon equation (massless Duffin-Kemmer-Petiau equation) is written expilicitly for general type of stationary G\"{o}del space-times and is solved exactly for G\"{o}del-type and G\"{o}del space-times. Harmonic oscillator behaviour of the solutions is discussed and energy spectrum of photon is obtained.Comment: 9 pages,RevTeX, no figure, revised for publicatio

On Equivalence of Duffin-Kemmer-Petiau and Klein-Gordon Equations

A strict proof of equivalence between Duffin-Kemmer-Petiau (DKP) and Klein-Gordon (KG) theories is presented for physical S-matrix elements in the case of charged scalar particles interacting in minimal way with an external or quantized electromagnetic field. First, Hamiltonian canonical approach to DKP theory is developed in both component and matrix form. The theory is then quantized through the construction of the generating functional for Green functions (GF) and the physical matrix elements of S-matrix are proved to be relativistic invariants. The equivalence between both theories is then proved using the connection between GF and the elements of S-matrix, including the case of only many photons states, and for more general conditions - so called reduction formulas of Lehmann, Symanzik, Zimmermann.Comment: 23 pages, no figures, requires macro tcilate

Boson-fermion unification, superstrings, and Bohmian mechanics

Bosonic and fermionic particle currents can be introduced in a more unified way, with the cost of introducing a preferred spacetime foliation. Such a unified treatment of bosons and fermions naturally emerges from an analogous superstring current, showing that the preferred spacetime foliation appears only at the level of effective field theory, not at the fundamental superstring level. The existence of the preferred spacetime foliation allows an objective definition of particles associated with quantum field theory in curved spacetime. Such an objective definition of particles makes the Bohmian interpretation of particle quantum mechanics more appealing. The superstring current allows a consistent Bohmian interpretation of superstrings themselves, including a Bohmian description of string creation and destruction in terms of string splitting. The Bohmian equations of motion and the corresponding probabilistic predictions are fully relativistic covariant and do not depend on the preferred foliation.Comment: 30 pages, 1 figure, revised, to appear in Found. Phy