The rapidly increasing emergence of antibiotic resistance amongst pathogenic bacteria is a major clinical and public health problem. The increase in resistant pathogens, accompanied with the small number of new antibiotics introduced in recent years, has limited the number of effective antimicrobials. The classical paradigm suggests that antibiotic resistance emerges by selection for pre-existing mutants in the bacterial population exposed to antibiotics. In contrast, recent data suggested that mutations evolve after cells encounter antibiotic therapy. This kind of mutation is known as adaptive mutation, which is activated by the SOS DNA repair and mutagenesis pathways. Accumulation of single-stranded DNA (ss-DNA) is the signal that induces the SOS response by promoting the formation of the RecA filament, which in turn activates the auto-cleavage activity of LexA and allows expression of SOS genes, including the SOS error-prone polymerases. In this project, phthalocyanine tetrasulfonic acid (PcTs)-based RecA inhibitors were characterized. PcTs molecules were found to potentiate the activity of bactericidal antibiotics and reduce the ability of bacteria to acquire antibiotic resistance mutations. This study highlights the ability of RecA inhibitors to potentiate the activity of antibiotics and provides a strategy for prolonging the life span of existing and newly developed antibiotics. We predicate that RecA inhibitors will be part of an antibiotic “cocktail” that enhances the activity of antibiotics and blocks resistance, which will ultimately prolong antibiotic lifespan.

Digital filters having sharp transition band play a vital role in modern digital signal processing (DSP) applications. Emerging technologies require digital filters to be both computationally efficient in software/hardware realizations. This thesis is concerned with the design and structural-level optimization of sharp transition band digital filters employing the well known frequency response masking (FRM) approach. Unlike the conventional finite impulse response (FIR) based FRM approach, the FRM technique used in this thesis incorporates infinite impulse response (IIR) digital interpolation subfilters, thereby reducing the overall filter order that results in a reduction of hardware complexity. Two realization methods are discussed in this thesis, namely, the bilinear-lossless-discrete-integrators (bilinear-LDI) digital filter design technique, and the lattice wave digital filter (lattice WDF) digital filter design technique. Diversity controlled (DC) genetic algorithm (GA) is employed to optimize both types of IIR based FRM digital filters over the efficient canonical signed digit (CSD) multiplier coefficient space. DCGAs represent FRM digital filters by a binary chromosome and proceed from a population pool of candidate chromosomes to future generations in order to arrive at the desired FRM digital filter satisfying the design specifications. A novel cost-function is used that allows the DCGA to simultaneously optimize both the amplitude-frequency and group-delay frequency response. A fast convergence speed has been observed. / Communications

No description available.

Staphylococcus aureus is a opportunistic pathogen that can cause severe and chronic infections. The reason of the infections relapse is often the persistence. It is about adapting to stressful conditions by inducing a dormant state, which would allow bacteria to survive exposure to antibiotics and grow again after their elimination. Bacteria that persist in the patient acquire various adaptive mutations, which are transmited creating subpopulations that have a better ability to persist. The aim of this diploma thesis was to compare individual methods of persistent study that could be used in clinical practice in the future, and at the same time to try a closer molecular characterization of the persistent state with using methods for calculating gene expression. I had chronological isolates of Staphylococcus aureus at my disposal, the initial one being the primoisolate, an isolate taken at the diagnostics of cystic fibrosis before the start of antibiotic treatment. Another was taken at a distance of three-quarters of a year and the last with a half-year interval from the previous one. Following whole genome sequencing, genes in which adaptive mutations occurred were identified. The first method determines the degree of persistence by calculating CFU (Colony Forming Units) after antibiotic treatment....

In clinical practice, infections caused by persistent bacteria have become a worldwide problem. We are talking about a subpopulation of cells that are able to withstand lethal doses of antibiotics and after their elimination are capable of resuscitation and re-induction of the disease. The opportunistic pathogen Staphylococcus aureus is one of this bacteria and causes various serious chronic infections. During the long-term persistence in patients, persistent bacteria acquire adaptive mutations. The aim of this diploma thesis was to monitor the degree of persistence in selected clinical isolates, and at the same time to demonstrate the effect of adaptive mutations on the degree of persistence as well as to molecularly characterize the persistent state by gene expression. I had chronological isolates of S. aureus at my disposal, the initial one being the primoisolate, an isolate taken at the diagnostics of cystic fibrosis before the start of antibiotic treatment. Another was taken at a distance of one year and the last with a half-year interval from the previous one. Following whole genome sequencing, genes in which adaptive mutations occurred were identified. The first method determines the degree of persistence by calculating CFU (Colony Forming Units) after antibiotic treatment. I found that this...