Marat Sadykov - Academia.edu (original) (raw)

Papers by Marat Sadykov

Machines

During the operation process of high-voltage insulators, the characteristics of assessing their t... more During the operation process of high-voltage insulators, the characteristics of assessing their technical state are evaluated by using remote contactless monitoring and by subsequent forecasting of their residual life based on the developed set of diagnostic parameters of critical defects. Special attention is paid to the challenges of the practical application for remote contactless monitoring of high-voltage insulators’ current operating state. Measurements of characteristics for partial discharges on high-voltage insulators with various types of critical defects taken by electromagnetic and acoustic sensors are described. Based on the measurements, it was found that the unusual properties of the PD begin to manifest themselves starting from the intensities q ≥ 1.5–2 nC, and their maximum intensity can reach 5–7 nC. Up to PD intensities q ≤ 3 nC, most parameters of PD characteristics measured by electromagnetic and acoustic sensors correspond with an accuracy of 70–90%. It was fou...

E3S Web of Conferences

The article substantiates the relevance of the inspection of overhead power lines by determining ... more The article substantiates the relevance of the inspection of overhead power lines by determining the mechanical loads of the conductors. The conductor sways under the action of external loads and variable internal mechanical loads. The conductor behaves in span like a pendulum. A model of the harmonic oscillations of the conductor in flight is derived to assess the mechanical loads of the conductor overhead power lines. This mathematical model is based on mathematical models of a flexible thread and a model of a physical pendulum. A conductor is a physical pendulum, where the conductor acts as the body, and in the role of the fixed axis of rotation, a straight line passing through the suspension points of the conductor. The article briefly describes an algorithm for calculating the conductor sag for the case when the conductor suspension points are at the same height. The results obtained using the developed model for calculating the sag of the conductor by its period are compared w...

Machines

The relevance of the problem is justified and the review of existing methods for determining the ... more The relevance of the problem is justified and the review of existing methods for determining the overhead line sag by the period of the conductor owned oscillations is conducted. The method of controlling the sag by the period of its own oscillations is briefly presented. The experimental installation for conducting full-scale tests is described, which includes the conductor (64 m), rigid fasteners at the points of conductor suspension, accelerometer, and temperature sensor mounted on the conductor, data from which are processed and recorded by the specialized software. The measurement method is explained with a detailed description. The conductor oscillations spectral analysis is performed. The results of experimental main harmonic frequency measurements, conductor, and changes in the sag are presented. A comparative results analysis showed the efficiency of the proposed method. The described method for determining the sag is easy to use (it is enough to install an accelerometer on...

Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invas... more Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting that S. aureus survives through the catabolism of secondary carbon sources. S. aureus encodes pathways to catabolize multiple amino acids, including those that generate pyruvate, 2-oxoglutarate, and oxaloacetate. To assess amino acid catabolism, S. aureus JE2 and mutants were grown in complete defined medium containing 18 amino acids but lacking glucose (CDM). A mutation in the gudB gene, coding for glutamate dehydrogenase, which generates 2-oxoglutarate from glutamate, significantly reduced growth in CDM, suggesting that glutamate and those amino acids generating glutamate, particularly proline, serve as the major carbon source in this medium. Nuclear magnetic resonance (NMR) studies confirmed this supposition. Furthermore, a mutation in the ackA gene, coding for acetate kin...

Lecture Notes in Mechanical Engineering

At present, the problem of timely examination of overhead transmission lines is acute. To solve i... more At present, the problem of timely examination of overhead transmission lines is acute. To solve it, devices with the ability to organize wireless data transmission without binding to transmitting stations were developed, including a set of sensors for measuring the parameters of diagnosed high voltage transmission lines. The use of modern electronic technologies and power schemes ensures the autonomy of the device, since it does not depend on external power sources, but makes power take-off directly from the line. Wireless data transmission is carried out with the help of the wireless network for process automation (WNPA) modules. Such a communication channel allows organizing not only inexpensive, but also capable of self-recovery network. The method of monitoring ice coating on overhead lines based on the mathematical model of chain line is considered. It allows identifying the current sag and elongation of the wire in a span, the force of its tension, taking into account the misa...

Vestnik MEI, 2020

Specialists of design and installation companies regularly face the need to select lighting devic... more Specialists of design and installation companies regularly face the need to select lighting devices, which often turns to be quite difficult task in connection with the modern state of the market of lighting production. Indeed, among the items presented in the market by the lighting equipment manufacturers, there is a noticeable share of lighting devices of degraded quality that have relatively poor lighting characteristics. Accordingly, since there is lack of confidence in the quality of some lighting products from individual manufacturers, there is a need of checking the technical parameters of LED products by the consumer himself, or by specialists of design and installation organizations. The aim of this study is to measure various lighting parameters of lighting devices equipped with semiconductor light sources for checking if the lighting parameters specified in the technical documentation are correct enough, and how reliably the LED-based lighting devices operate under differ...

E3S Web of Conferences, 2020

Complex remote monitoring and the developed non-contact diagnostic device (NDD) allow monitoring ... more Complex remote monitoring and the developed non-contact diagnostic device (NDD) allow monitoring the technical condition and revealing the residual life of high-voltage dielectric elements. It is based on non-contact remote periodic measurement of a set of diagnostic parameters (characteristics of electrical discharges emitted by insulators during operation) necessary for a reliable assessment of the operating state of high-voltage dielectric equipment at the moment of operation and determination of its residual life. NDDs are installed on each phase conductor and used to measure diagnostic parameters, followed by computer processing of the accumulated information signals. An analysis of the set of necessary diagnostic parameters makes it possible to form a conclusion on the degree of performance of dielectric elements. The paper considers a method for detecting defective high-voltage insulators using the developed non-contact diagnostic devices by the radio frequency method and ass...

Frontiers in Chemistry, 2020

Fast and reliable identification of infectious disease agents is among the most important challen... more Fast and reliable identification of infectious disease agents is among the most important challenges for the healthcare system. The discrimination of individual components of mixed infections represents a particularly difficult task. In the current study we further expand the functionality of a ratiometric sensor array technology based on small-molecule environmentally-sensitive organic dyes, which can be successfully applied for the analysis of mixed bacterial samples. Using pattern recognition methods and data from pure bacterial species, we demonstrate that this approach can be used to quantify the composition of mixtures, as well as to predict their components with the accuracy of ∼80% without the need to acquire additional reference data. The described approach significantly expands the functionality of sensor arrays and provides important insights into data processing for the analysis of other complex samples.

Mining Equipment and Electromechanics, 2019

mBio, 2017

Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invas... more Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting that S. aureus survives through the catabolism of secondary carbon sources. S. aureus encodes pathways to catabolize multiple amino acids, including those that generate pyruvate, 2-oxoglutarate, and oxaloacetate. To assess amino acid catabolism, S. aureus JE2 and mutants were grown in complete defined medium containing 18 amino acids but lacking glucose (CDM). A mutation in the gudB gene, coding for glutamate dehydrogenase, which generates 2-oxoglutarate from glutamate, significantly reduced growth in CDM, suggesting that glutamate and those amino acids generating glutamate, particularly proline, serve as the major carbon source in this medium. Nuclear magnetic resonance (NMR) studies confirmed this supposition. Furthermore, a mutation in the ackA gene, coding for acetate kin...

PLoS pathogens, 2014

Similar to developmental programs in eukaryotes, the death of a subpopulation of cells is thought... more Similar to developmental programs in eukaryotes, the death of a subpopulation of cells is thought to benefit bacterial biofilm development. However mechanisms that mediate a tight control over cell death are not clearly understood at the population level. Here we reveal that CidR dependent pyruvate oxidase (CidC) and α-acetolactate synthase/decarboxylase (AlsSD) overflow metabolic pathways, which are active during staphylococcal biofilm development, modulate cell death to achieve optimal biofilm biomass. Whereas acetate derived from CidC activity potentiates cell death in cells by a mechanism dependent on intracellular acidification and respiratory inhibition, AlsSD activity effectively counters CidC action by diverting carbon flux towards neutral rather than acidic byproducts and consuming intracellular protons in the process. Furthermore, the physiological features that accompany metabolic activation of cell death bears remarkable similarities to hallmarks of eukaryotic programmed...

Microbiology, 2011

Staphylococcus epidermidis is an opportunistic bacterium whose infections often involve the forma... more Staphylococcus epidermidis is an opportunistic bacterium whose infections often involve the formation of a biofilm on implanted biomaterials. In S. epidermidis, the exopolysaccharide facilitating bacterial adherence in a biofilm is polysaccharide intercellular adhesin (PIA), whose synthesis requires the enzymes encoded within the intercellular adhesin operon (icaADBC). In vitro, the formation of S. epidermidis biofilms is enhanced by conditions that repress tricarboxylic acid (TCA) cycle activity, such as growth in a medium containing glucose. In many Gram-positive bacteria, repression of TCA cycle genes in response to glucose is accomplished by catabolite control protein A (CcpA). CcpA is a member of the GalR–LacI repressor family that mediates carbon catabolite repression, leading us to hypothesize that catabolite control of S. epidermidis biofilm formation is indirectly regulated by CcpA-dependent repression of the TCA cycle. To test this hypothesis, ccpA deletion mutants were co...

mBio, 2013

A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to... more A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these antibiotics. The increased protection from β-lactam antibiotics could result from pleiotropic effects of a dysfunctional TCA cycle, including increased resistance to oxidative stress, reduced susceptibility to autolysis, and a more positively charged cell surface. IMPORTANCE Staphylococcus epidermidis , a normal...

Journal of Biological Chemistry, 2010

Journal of Bacteriology, 2010

More than 200 direct CodY target genes in Staphylococcus aureus were identified by genome-wide an... more More than 200 direct CodY target genes in Staphylococcus aureus were identified by genome-wide analysis of in vitro DNA binding. This analysis, which was confirmed for some genes by DNase I footprinting assays, revealed that CodY is a direct regulator of numerous transcription units associated with amino acid biosynthesis, transport of macromolecules, and virulence. The virulence genes regulated by CodY fell into three groups. One group was dependent on the Agr system for its expression; these genes were indirectly regulated by CodY through its repression of the agr locus. A second group was regulated directly by CodY. The third group, which includes genes for alpha-toxin and capsule synthesis, was regulated by CodY in two ways, i.e., by direct repression and by repression of the agr locus. Since S. aureus CodY was activated in vitro by the branched chain amino acids and GTP, CodY appears to link changes in intracellular metabolite pools with the induction of numerous adaptive respo...

Journal of Bacteriology, 2013

During growth under conditions of glucose and oxygen excess, Staphylococcus aureus predominantly ... more During growth under conditions of glucose and oxygen excess, Staphylococcus aureus predominantly accumulates acetate in the culture medium, suggesting that the phosphotransacetylase-acetate kinase (Pta-AckA) pathway plays a crucial role in bacterial fitness. Previous studies demonstrated that these conditions also induce the S. aureus CidR regulon involved in the control of cell death. Interestingly, the CidR regulon is comprised of only two operons, both encoding pyruvate catabolic enzymes, suggesting an intimate relationship between pyruvate metabolism and cell death. To examine this relationship, we introduced ackA and pta mutations in S. aureus and tested their effects on bacterial growth, carbon and energy metabolism, cid expression, and cell death. Inactivation of the Pta-AckA pathway showed a drastic inhibitory effect on growth and caused accumulation of dead cells in both pta and ackA mutants. Surprisingly, inactivation of the Pta-AckA pathway did not lead to a decrease in t...

Journal of Bacteriology, 2010

Staphylococcus aureus capsule synthesis requires the precursor N -acetyl-glucosamine; however, ca... more Staphylococcus aureus capsule synthesis requires the precursor N -acetyl-glucosamine; however, capsule is synthesized during post-exponential growth when the availability of N -acetyl-glucosamine is limited. Capsule biosynthesis also requires aerobic respiration, leading us to hypothesize that capsule synthesis requires tricarboxylic acid cycle intermediates. Consistent with this hypothesis, S. aureus tricarboxylic acid cycle mutants fail to make capsule.

Journal of Bacteriology, 2008

Staphylococcus epidermidis is a major nosocomial pathogen primarily infecting immunocompromised i... more Staphylococcus epidermidis is a major nosocomial pathogen primarily infecting immunocompromised individuals or those with implanted biomaterials (e.g., catheters). Biomaterial-associated infections often involve the formation of a biofilm on the surface of the medical device. In S. epidermidis , polysaccharide intercellular adhesin (PIA) is an important mediator of biofilm formation and pathogenesis. Synthesis of PIA is regulated by at least three DNA binding proteins (IcaR, SarA, and σ B ) and several environmental and nutritional conditions. Previously, we observed the environmental conditions that increased PIA synthesis decreased tricarboxylic acid (TCA) cycle activity. In this study, S. epidermidis TCA cycle mutants were constructed, and the function of central metabolism in PIA biosynthesis was examined. TCA cycle inactivation altered the metabolic status of S. epidermidis , resulting in a massive derepression of PIA biosynthetic genes and a redirection of carbon from growth i...

Infection and Immunity, 2009

Staphylococci are the leading causes of endovascular infections worldwide. Commonly, these infect... more Staphylococci are the leading causes of endovascular infections worldwide. Commonly, these infections involve the formation of biofilms on the surface of biomaterials. Biofilms are a complex aggregation of bacteria commonly encapsulated by an adhesive exopolysaccharide matrix. In staphylococci, this exopolysaccharide matrix is composed of polysaccharide intercellular adhesin (PIA). PIA is synthesized when the tricarboxylic acid (TCA) cycle is repressed. The inverse correlation between PIA synthesis and TCA cycle activity led us to hypothesize that increasing TCA cycle activity would decrease PIA synthesis and biofilm formation and reduce virulence in a rabbit catheter-induced model of biofilm infection. TCA cycle activity can be induced by preventing staphylococci from exogenously acquiring a TCA cycle-derived amino acid necessary for growth. To determine if TCA cycle induction would decrease PIA synthesis in Staphylococcus aureus , the glutamine permease gene ( glnP ) was inactivat...

Machines

During the operation process of high-voltage insulators, the characteristics of assessing their t... more During the operation process of high-voltage insulators, the characteristics of assessing their technical state are evaluated by using remote contactless monitoring and by subsequent forecasting of their residual life based on the developed set of diagnostic parameters of critical defects. Special attention is paid to the challenges of the practical application for remote contactless monitoring of high-voltage insulators’ current operating state. Measurements of characteristics for partial discharges on high-voltage insulators with various types of critical defects taken by electromagnetic and acoustic sensors are described. Based on the measurements, it was found that the unusual properties of the PD begin to manifest themselves starting from the intensities q ≥ 1.5–2 nC, and their maximum intensity can reach 5–7 nC. Up to PD intensities q ≤ 3 nC, most parameters of PD characteristics measured by electromagnetic and acoustic sensors correspond with an accuracy of 70–90%. It was fou...

E3S Web of Conferences

The article substantiates the relevance of the inspection of overhead power lines by determining ... more The article substantiates the relevance of the inspection of overhead power lines by determining the mechanical loads of the conductors. The conductor sways under the action of external loads and variable internal mechanical loads. The conductor behaves in span like a pendulum. A model of the harmonic oscillations of the conductor in flight is derived to assess the mechanical loads of the conductor overhead power lines. This mathematical model is based on mathematical models of a flexible thread and a model of a physical pendulum. A conductor is a physical pendulum, where the conductor acts as the body, and in the role of the fixed axis of rotation, a straight line passing through the suspension points of the conductor. The article briefly describes an algorithm for calculating the conductor sag for the case when the conductor suspension points are at the same height. The results obtained using the developed model for calculating the sag of the conductor by its period are compared w...

Machines

The relevance of the problem is justified and the review of existing methods for determining the ... more The relevance of the problem is justified and the review of existing methods for determining the overhead line sag by the period of the conductor owned oscillations is conducted. The method of controlling the sag by the period of its own oscillations is briefly presented. The experimental installation for conducting full-scale tests is described, which includes the conductor (64 m), rigid fasteners at the points of conductor suspension, accelerometer, and temperature sensor mounted on the conductor, data from which are processed and recorded by the specialized software. The measurement method is explained with a detailed description. The conductor oscillations spectral analysis is performed. The results of experimental main harmonic frequency measurements, conductor, and changes in the sag are presented. A comparative results analysis showed the efficiency of the proposed method. The described method for determining the sag is easy to use (it is enough to install an accelerometer on...

Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invas... more Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting that S. aureus survives through the catabolism of secondary carbon sources. S. aureus encodes pathways to catabolize multiple amino acids, including those that generate pyruvate, 2-oxoglutarate, and oxaloacetate. To assess amino acid catabolism, S. aureus JE2 and mutants were grown in complete defined medium containing 18 amino acids but lacking glucose (CDM). A mutation in the gudB gene, coding for glutamate dehydrogenase, which generates 2-oxoglutarate from glutamate, significantly reduced growth in CDM, suggesting that glutamate and those amino acids generating glutamate, particularly proline, serve as the major carbon source in this medium. Nuclear magnetic resonance (NMR) studies confirmed this supposition. Furthermore, a mutation in the ackA gene, coding for acetate kin...

Lecture Notes in Mechanical Engineering

At present, the problem of timely examination of overhead transmission lines is acute. To solve i... more At present, the problem of timely examination of overhead transmission lines is acute. To solve it, devices with the ability to organize wireless data transmission without binding to transmitting stations were developed, including a set of sensors for measuring the parameters of diagnosed high voltage transmission lines. The use of modern electronic technologies and power schemes ensures the autonomy of the device, since it does not depend on external power sources, but makes power take-off directly from the line. Wireless data transmission is carried out with the help of the wireless network for process automation (WNPA) modules. Such a communication channel allows organizing not only inexpensive, but also capable of self-recovery network. The method of monitoring ice coating on overhead lines based on the mathematical model of chain line is considered. It allows identifying the current sag and elongation of the wire in a span, the force of its tension, taking into account the misa...

Vestnik MEI, 2020

Specialists of design and installation companies regularly face the need to select lighting devic... more Specialists of design and installation companies regularly face the need to select lighting devices, which often turns to be quite difficult task in connection with the modern state of the market of lighting production. Indeed, among the items presented in the market by the lighting equipment manufacturers, there is a noticeable share of lighting devices of degraded quality that have relatively poor lighting characteristics. Accordingly, since there is lack of confidence in the quality of some lighting products from individual manufacturers, there is a need of checking the technical parameters of LED products by the consumer himself, or by specialists of design and installation organizations. The aim of this study is to measure various lighting parameters of lighting devices equipped with semiconductor light sources for checking if the lighting parameters specified in the technical documentation are correct enough, and how reliably the LED-based lighting devices operate under differ...

E3S Web of Conferences, 2020

Complex remote monitoring and the developed non-contact diagnostic device (NDD) allow monitoring ... more Complex remote monitoring and the developed non-contact diagnostic device (NDD) allow monitoring the technical condition and revealing the residual life of high-voltage dielectric elements. It is based on non-contact remote periodic measurement of a set of diagnostic parameters (characteristics of electrical discharges emitted by insulators during operation) necessary for a reliable assessment of the operating state of high-voltage dielectric equipment at the moment of operation and determination of its residual life. NDDs are installed on each phase conductor and used to measure diagnostic parameters, followed by computer processing of the accumulated information signals. An analysis of the set of necessary diagnostic parameters makes it possible to form a conclusion on the degree of performance of dielectric elements. The paper considers a method for detecting defective high-voltage insulators using the developed non-contact diagnostic devices by the radio frequency method and ass...

Frontiers in Chemistry, 2020

Fast and reliable identification of infectious disease agents is among the most important challen... more Fast and reliable identification of infectious disease agents is among the most important challenges for the healthcare system. The discrimination of individual components of mixed infections represents a particularly difficult task. In the current study we further expand the functionality of a ratiometric sensor array technology based on small-molecule environmentally-sensitive organic dyes, which can be successfully applied for the analysis of mixed bacterial samples. Using pattern recognition methods and data from pure bacterial species, we demonstrate that this approach can be used to quantify the composition of mixtures, as well as to predict their components with the accuracy of ∼80% without the need to acquire additional reference data. The described approach significantly expands the functionality of sensor arrays and provides important insights into data processing for the analysis of other complex samples.

Mining Equipment and Electromechanics, 2019

mBio, 2017

Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invas... more Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting that S. aureus survives through the catabolism of secondary carbon sources. S. aureus encodes pathways to catabolize multiple amino acids, including those that generate pyruvate, 2-oxoglutarate, and oxaloacetate. To assess amino acid catabolism, S. aureus JE2 and mutants were grown in complete defined medium containing 18 amino acids but lacking glucose (CDM). A mutation in the gudB gene, coding for glutamate dehydrogenase, which generates 2-oxoglutarate from glutamate, significantly reduced growth in CDM, suggesting that glutamate and those amino acids generating glutamate, particularly proline, serve as the major carbon source in this medium. Nuclear magnetic resonance (NMR) studies confirmed this supposition. Furthermore, a mutation in the ackA gene, coding for acetate kin...

PLoS pathogens, 2014

Similar to developmental programs in eukaryotes, the death of a subpopulation of cells is thought... more Similar to developmental programs in eukaryotes, the death of a subpopulation of cells is thought to benefit bacterial biofilm development. However mechanisms that mediate a tight control over cell death are not clearly understood at the population level. Here we reveal that CidR dependent pyruvate oxidase (CidC) and α-acetolactate synthase/decarboxylase (AlsSD) overflow metabolic pathways, which are active during staphylococcal biofilm development, modulate cell death to achieve optimal biofilm biomass. Whereas acetate derived from CidC activity potentiates cell death in cells by a mechanism dependent on intracellular acidification and respiratory inhibition, AlsSD activity effectively counters CidC action by diverting carbon flux towards neutral rather than acidic byproducts and consuming intracellular protons in the process. Furthermore, the physiological features that accompany metabolic activation of cell death bears remarkable similarities to hallmarks of eukaryotic programmed...

Microbiology, 2011

Staphylococcus epidermidis is an opportunistic bacterium whose infections often involve the forma... more Staphylococcus epidermidis is an opportunistic bacterium whose infections often involve the formation of a biofilm on implanted biomaterials. In S. epidermidis, the exopolysaccharide facilitating bacterial adherence in a biofilm is polysaccharide intercellular adhesin (PIA), whose synthesis requires the enzymes encoded within the intercellular adhesin operon (icaADBC). In vitro, the formation of S. epidermidis biofilms is enhanced by conditions that repress tricarboxylic acid (TCA) cycle activity, such as growth in a medium containing glucose. In many Gram-positive bacteria, repression of TCA cycle genes in response to glucose is accomplished by catabolite control protein A (CcpA). CcpA is a member of the GalR–LacI repressor family that mediates carbon catabolite repression, leading us to hypothesize that catabolite control of S. epidermidis biofilm formation is indirectly regulated by CcpA-dependent repression of the TCA cycle. To test this hypothesis, ccpA deletion mutants were co...

mBio, 2013

A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to... more A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these antibiotics. The increased protection from β-lactam antibiotics could result from pleiotropic effects of a dysfunctional TCA cycle, including increased resistance to oxidative stress, reduced susceptibility to autolysis, and a more positively charged cell surface. IMPORTANCE Staphylococcus epidermidis , a normal...

Journal of Biological Chemistry, 2010

Journal of Bacteriology, 2010

More than 200 direct CodY target genes in Staphylococcus aureus were identified by genome-wide an... more More than 200 direct CodY target genes in Staphylococcus aureus were identified by genome-wide analysis of in vitro DNA binding. This analysis, which was confirmed for some genes by DNase I footprinting assays, revealed that CodY is a direct regulator of numerous transcription units associated with amino acid biosynthesis, transport of macromolecules, and virulence. The virulence genes regulated by CodY fell into three groups. One group was dependent on the Agr system for its expression; these genes were indirectly regulated by CodY through its repression of the agr locus. A second group was regulated directly by CodY. The third group, which includes genes for alpha-toxin and capsule synthesis, was regulated by CodY in two ways, i.e., by direct repression and by repression of the agr locus. Since S. aureus CodY was activated in vitro by the branched chain amino acids and GTP, CodY appears to link changes in intracellular metabolite pools with the induction of numerous adaptive respo...

Journal of Bacteriology, 2013

During growth under conditions of glucose and oxygen excess, Staphylococcus aureus predominantly ... more During growth under conditions of glucose and oxygen excess, Staphylococcus aureus predominantly accumulates acetate in the culture medium, suggesting that the phosphotransacetylase-acetate kinase (Pta-AckA) pathway plays a crucial role in bacterial fitness. Previous studies demonstrated that these conditions also induce the S. aureus CidR regulon involved in the control of cell death. Interestingly, the CidR regulon is comprised of only two operons, both encoding pyruvate catabolic enzymes, suggesting an intimate relationship between pyruvate metabolism and cell death. To examine this relationship, we introduced ackA and pta mutations in S. aureus and tested their effects on bacterial growth, carbon and energy metabolism, cid expression, and cell death. Inactivation of the Pta-AckA pathway showed a drastic inhibitory effect on growth and caused accumulation of dead cells in both pta and ackA mutants. Surprisingly, inactivation of the Pta-AckA pathway did not lead to a decrease in t...

Journal of Bacteriology, 2010

Staphylococcus aureus capsule synthesis requires the precursor N -acetyl-glucosamine; however, ca... more Staphylococcus aureus capsule synthesis requires the precursor N -acetyl-glucosamine; however, capsule is synthesized during post-exponential growth when the availability of N -acetyl-glucosamine is limited. Capsule biosynthesis also requires aerobic respiration, leading us to hypothesize that capsule synthesis requires tricarboxylic acid cycle intermediates. Consistent with this hypothesis, S. aureus tricarboxylic acid cycle mutants fail to make capsule.

Journal of Bacteriology, 2008

Staphylococcus epidermidis is a major nosocomial pathogen primarily infecting immunocompromised i... more Staphylococcus epidermidis is a major nosocomial pathogen primarily infecting immunocompromised individuals or those with implanted biomaterials (e.g., catheters). Biomaterial-associated infections often involve the formation of a biofilm on the surface of the medical device. In S. epidermidis , polysaccharide intercellular adhesin (PIA) is an important mediator of biofilm formation and pathogenesis. Synthesis of PIA is regulated by at least three DNA binding proteins (IcaR, SarA, and σ B ) and several environmental and nutritional conditions. Previously, we observed the environmental conditions that increased PIA synthesis decreased tricarboxylic acid (TCA) cycle activity. In this study, S. epidermidis TCA cycle mutants were constructed, and the function of central metabolism in PIA biosynthesis was examined. TCA cycle inactivation altered the metabolic status of S. epidermidis , resulting in a massive derepression of PIA biosynthetic genes and a redirection of carbon from growth i...

Infection and Immunity, 2009

Staphylococci are the leading causes of endovascular infections worldwide. Commonly, these infect... more Staphylococci are the leading causes of endovascular infections worldwide. Commonly, these infections involve the formation of biofilms on the surface of biomaterials. Biofilms are a complex aggregation of bacteria commonly encapsulated by an adhesive exopolysaccharide matrix. In staphylococci, this exopolysaccharide matrix is composed of polysaccharide intercellular adhesin (PIA). PIA is synthesized when the tricarboxylic acid (TCA) cycle is repressed. The inverse correlation between PIA synthesis and TCA cycle activity led us to hypothesize that increasing TCA cycle activity would decrease PIA synthesis and biofilm formation and reduce virulence in a rabbit catheter-induced model of biofilm infection. TCA cycle activity can be induced by preventing staphylococci from exogenously acquiring a TCA cycle-derived amino acid necessary for growth. To determine if TCA cycle induction would decrease PIA synthesis in Staphylococcus aureus , the glutamine permease gene ( glnP ) was inactivat...