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Zoltan G. Varga

Bio: Zoltan G. Varga is an academic researcher from University of Szeged. The author has contributed to research in topics: Quorum sensing & Quorum Quenching. The author has an hindex of 4, co-authored 4 publications receiving 72 citations.

Papers
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Journal Article
01 Mar 2012-in Vivo
TL;DR: Results show that TFs have QS inhibitory properties that are mediated through their inhibition of efflux pumps that extrude the noxious QS signal before it reaches its intended target.
Abstract: Background: One major microbiological problem is the widespread antibiotic resistance. There is an urgent need for new antibiotics and ways to treat multi-drug- resistant infections. Inhibition of bacterial quorum sensing (QS) systems could be an effective alternative in a smuch as they regulate a broad spectrum of cell functions, including, virulence factor production, biofilm organisation and motility. Influx and efflux bacterial systems involved in quorum sensing (QS) are known to depend on the proton motive force (PMF). Thus, a new series of 12 trifluoromethyl ketones (TFs) known to inhibit the PMF, was investigated for effects on the efflux pump of a QS responding bacterium, for its subsequent effect on the response to a QS signal and its direct inhibition of the response to a QS signal. Materials and Methods: Chromobacterium violaceum 026 (CV026) was used as the indicator strain to evaluate the QS inhibitory effect of TFs. This strain responds to the presence of short carbon chain acyl-homoserine lactones (AHLs) by the development of a purple pigment. Effect on the QS response of CV026 to externally added AHLs was evaluated. In addition, the specific activity of the TFs on the efflux pump system of the CV026 strain and a wild-type Escherichia coli strain was assessed with the aid of the automated real-time ethidium bromide method. Results: From the 12 compounds, 6 proved to be effective inhibitors of the QS response by CV026, as well as inhibit the efflux pumps of CV026 and Escherichia coli. Conclusion: Our results show that TFs have QS inhibitory properties that are mediated through their inhibition of efflux pumps that extrude the noxious QS signal before it reaches its intended target. Because the TFs also inhibit the efflux pump of a pathogenic bacterium, the method used for the evaluation of the TFs in the current study has clinical relevance and may be exploited for the prevention of QS responses of infecting bacteria. The antimicrobial and antimotility effects of 30 trifluoromethyl ketones (TFs) on various bacterial species have already been studied (1-5). Some of these TFs only inhibit the growth of

45 citations

Book ChapterDOI
14 Jan 2011
TL;DR: In this paper, the authors show that during tumor growth, there are many differences between the healthy tissues and the growing tumor, including metabolic, structural and thermodynamic differences, for heat production.
Abstract: The human organism continuously takes up nutrients to build up macromolecules and functionally active structures. On the basis of the first law of thermodynamics, the energy of nutrients is transformed, proceeding toward minimum entropy production and the release of heat and “waste products” in the open system. Part of the heat produced during exothermic processes supports the optimal efficiency of the endothermic biological reactions in the organism, and the rest is dissipated in the environment on the basis of the Second Law of Thermodynamics. In contrast with the living state, cancers live on the energy and mass of the organism as a parasite metabolizing and destroying the tissues of the organism according to the Second Law of Thermodynamics. Schroedinger put the question of whether life is based on the laws of physics. He suggested that: chemical processes lead to entropy production, which is a direct measure of molecular disorder (1). At the end of his book, he summarized his view: “We must therefore not be discouraged by the difficulty in interpreting life by the ordinary laws of physics” (1). Where processes under conditions far from equilibrium correspond to an interplay between chance and necessity, between deterministic laws and fluctuations (2, 3). During tumor growth, there are many differences between the healthy tissues and the growing tumor, including metabolic, structural and thermodynamic differences, for heat production. Both structural differences and heat formation can be used to follow the entropy differences between cancerous and nomal tissues. These entropy changes can be followed by various methods, e.g. histology and thermography. In general, the calculation of entropy production due to thermal fluxes based on temperature differences and, similarly, differences in other entropy-producing processes as driving forces are promising as potential targets for tumor demarcation (2-4).

12 citations

Journal ArticleDOI
TL;DR: The signal of QS transmission between the co-existing QS system and pathogenic bacteria isolated from various patients was found to be modified by certain bacterial cells, which can change the classical signal transmission in the microbial community and should therefore be taken into consideration in rational chemotherapy.
Abstract: Antibiotics are usually studied on pure cultures of a single bacterial strain, whereas multi-species communities that inhabit human niches and the biosphere are generally ignored. The modification of quorum sensing (QS) is investigated in a system involving a co-existing signal producer and sensor bacterial cells. A pure culture of merely one bacterial species is quite rare in any niche. The interactions of different bacterial species may therefore be of special importance in pathogenicity, antibiotic resistance and signal transmission.In the present study the authors investigated the QS in model experiments involving several Gram-positive and Gram-negative bacterial species isolated from human infections or laboratory strains. The effects of various compounds on QS were studied in mixed bacterial populations during the incubation period of 24–48 h. As the simplest example of co-existing cell populations, the N-acyl homoserine lactone producing Ezf 10–17 was applied with Chromobacterium violaceum 026 as s...

6 citations


Cited by
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Journal ArticleDOI
TL;DR: This review considers how bacterial virulence and fitness are affected by antibiotic resistance and also how the relationship between virulent and resistance is affected by different genetic mechanisms and by the most prevalent global responses.
Abstract: Hosts and bacteria have coevolved over millions of years, during which pathogenic bacteria have modified their virulence mechanisms to adapt to host defense systems. Although the spread of pathogens has been hindered by the discovery and widespread use of antimicrobial agents, antimicrobial resistance has increased globally. The emergence of resistant bacteria has accelerated in recent years, mainly as a result of increased selective pressure. However, although antimicrobial resistance and bacterial virulence have developed on different timescales, they share some common characteristics. This review considers how bacterial virulence and fitness are affected by antibiotic resistance and also how the relationship between virulence and resistance is affected by different genetic mechanisms (e.g., coselection and compensatory mutations) and by the most prevalent global responses. The interplay between these factors and the associated biological costs depend on four main factors: the bacterial species involved, virulence and resistance mechanisms, the ecological niche, and the host. The development of new strategies involving new antimicrobials or nonantimicrobial compounds and of novel diagnostic methods that focus on high-risk clones and rapid tests to detect virulence markers may help to resolve the increasing problem of the association between virulence and resistance, which is becoming more beneficial for pathogenic bacteria.

739 citations

01 Jan 1995
TL;DR: This study has demonstrated that the synthesis of Staphylococcus aureus virulence factors is controlled by a density-sensing system that utilizes an octapeptide produced by the organism itself.
Abstract: Some bacterial pathogens elaborate and secrete virulence factors in response to environmental signals, others in response to a specific host product, and still others in response to no discernible cue. In this study, we have demonstrated that the synthesis of Staphylococcus aureus virulence factors is controlled by a density-sensing system that utilizes an octapeptide produced by the organism itself. The octapeptide activates expression of the agr locus, a global regulator of the virulence response. This response involves the reciprocal regulation of genes encoding surface proteins and those encoding secreted virulence factors. As cells enter the postexponential phase, surface protein genes are repressed by agr and secretory protein genes are subsequently activated. The intracellular agr effector is a regulatory RNA, RNAIII, whose transcription is activated by an agr-encoded signal transduction system for which the octapeptide is the ligand.

601 citations

Journal ArticleDOI
TL;DR: The definition of an efflux pump inhibitor (EPI) includes the ability to render the bacterium increasingly more sensitive to a given antibiotic or even reverse the multidrug resistant phenotype.
Abstract: Multidrug resistance (MDR) has appeared in response to selective pressures resulting from the incorrect use of antibiotics and other antimicrobials. This inappropriate application and mismanagement of antibiotics have led to serious problems in the therapy of infectious diseases. Bacteria can develop resistance by various mechanisms and one of the most important factors resulting in MDR is efflux pump-mediated resistance. Because of the importance of the efflux-related multidrug resistance the development of new therapeutic approaches aiming to inhibit bacterial efflux pumps is a promising way to combat bacteria having over-expressed MDR efflux systems. The definition of an efflux pump inhibitor (EPI) includes the ability to render the bacterium increasingly more sensitive to a given antibiotic or even reverse the multidrug resistant phenotype. In the recent years numerous EPIs have been developed, although so far their clinical application has not yet been achieved due to their in vivo toxicity and side effects. In this review, we aim to give a short overview of efflux mediated resistance in bacteria, EPI compounds of plant and synthetic origin, and the possible methods to investigate and screen EPI compounds in bacterial systems.

136 citations

Journal ArticleDOI
TL;DR: A potential role of the AdeFGH efflux pump in the synthesis and transport of autoinducer molecules during biofilm formation is demonstrated, suggesting a link between low-dose antimicrobial therapy and a high risk of biofilm infections caused by A. baumannii.
Abstract: Chronic wound infections are associated with biofilm formation, which in turn has been correlated with drug resistance. However, the mechanism by which bacteria form biofilms in clinical environments is not clearly understood. This study was designed to investigate the biofilm formation potency of Acinetobacter baumannii and the potential association of biofilm formation with genes encoding efflux pumps, quorum-sensing regulators, and outer membrane proteins. A total of 48 clinically isolated A. baumannii strains, identified by enterobacterial repetitive intergenic consensus (ERIC)-PCR as types A-II, A-III, and A-IV, were analyzed. Three representative strains, which were designated A. baumannii ABR2, ABR11, and ABS17, were used to evaluate antimicrobial susceptibility, biofilm inducibility, and gene transcription (abaI, adeB, adeG, adeJ, carO, and ompA). A significant increase in the MICs of different classes of antibiotics was observed in the biofilm cells. The formation of a biofilm was significantly induced in all the representative strains exposed to levofloxacin. The levels of gene transcription varied between bacterial genotypes, antibiotics, and antibiotic concentrations. The upregulation of adeG correlated with biofilm induction. The consistent upregulation of adeG and abaI was detected in A-III-type A. baumannii in response to levofloxacin and meropenem (1/8 to 1/2× the MIC), conditions which resulted in the greatest extent of biofilm induction. This study demonstrates a potential role of the AdeFGH efflux pump in the synthesis and transport of autoinducer molecules during biofilm formation, suggesting a link between low-dose antimicrobial therapy and a high risk of biofilm infections caused by A. baumannii. This study provides useful information for the development of antibiofilm strategies.

133 citations

Journal ArticleDOI
TL;DR: The relationship of the efflux pump (EP) system of Gram-negative bacteria to other antibiotic resistance mechanisms of the bacterium such as quorum sensing, biofilms, two component regulons, etc is discussed.
Abstract: This review discusses the relationship of the efflux pump (EP) system of Gram-negative bacteria to other antibiotic resistance mechanisms of the bacterium such as quorum sensing, biofilms, two component regulons, etc. The genetic responses of a Gram-negative to an antibiotic that render it immune to an antibiotic are also discussed. Lastly, the methods that have been developed for the identification of bacteria that over-express their EP system are presented in detail. Phenothiazines are well-known antipsychotic drugs with reported activity against bacterial EPs and other ancillary antibiotic mechanisms of the organism. Therefore these compounds will also be discussed.

120 citations