Małgorzata Korycka-Machała - Academia.edu (original) (raw)

Papers by Małgorzata Korycka-Machała

Bioorganic Chemistry, Dec 31, 2023

Antimicrobial Agents and Chemotherapy, Aug 1, 2007

Mycobacteria contain genes for several DNA ligases, including ligA, which encodes a NAD ؉-depende... more Mycobacteria contain genes for several DNA ligases, including ligA, which encodes a NAD ؉-dependent enzyme that has been postulated to be a target for novel antibacterial compounds. Using a homologous recombination system, direct evidence is presented that wild-type ligA cannot be deleted from the chromosome of Mycobacterium smegmatis. Deletions of native ligA in M. smegmatis could be obtained only after the integration of an extra copy of M. smegmatis or Mycobacterium tuberculosis ligA into the attB site of the chromosome, with expression controlled by chemically inducible promoters. The four ATP-dependent DNA ligases encoded by the M. smegmatis chromosome were unable to replace the function of LigA. Interestingly, the LigA protein from M. smegmatis could be substituted with the NAD ؉-dependent DNA ligase of Escherichia coli or the ATP-dependent ligase of bacteriophage T4. The conditional mutant strains allowed the analysis of the effect of LigA depletion on the growth of M. smegmatis. The protein level of the conditional mutants was estimated by Western blot analysis using antibodies raised against LigA of M. tuberculosis. This revealed that a strong overproduction or depletion of LigA did not affect the growth or survival of mycobacteria under standard laboratory conditions. In conclusion, although NAD ؉-dependent DNA ligase is essential for mycobacterial viability, only low levels of protein are required for growth. These findings suggest that very efficient inhibition of enzyme activity would be required if NAD ؉-dependent DNA ligase is to be useful as an antibiotic target in mycobacteria. The strains developed here will provide useful tools for the evaluation of the efficacy of any appropriate compounds in mycobacteria.

PLoS ONE, 2012

Repetitive DNA sequences with the potential to form alternative DNA conformations, such as slippe... more Repetitive DNA sequences with the potential to form alternative DNA conformations, such as slipped structures and cruciforms, can induce genetic instability by promoting replication errors and by serving as a substrate for DNA repair proteins, which may lead to DNA double-strand breaks (DSBs). However, the contribution of each of the DSB repair pathways, homologous recombination (HR), non-homologous end-joining (NHEJ) and single-strand annealing (SSA), to this sort of genetic instability is not fully understood. Herein, we assessed the genome-wide distribution of repetitive DNA sequences in the Mycobacterium smegmatis, Mycobacterium tuberculosis and Escherichia coli genomes, and determined the types and frequencies of genetic instability induced by direct and inverted repeats, both in the presence and in the absence of HR, NHEJ, and SSA. All three genomes are strongly enriched in direct repeats and modestly enriched in inverted repeats. When using chromosomally integrated constructs in M. smegmatis, direct repeats induced the perfect deletion of their intervening sequences ,1,000-fold above background. Absence of HR further enhanced these perfect deletions, whereas absence of NHEJ or SSA had no influence, suggesting compromised replication fidelity. In contrast, inverted repeats induced perfect deletions only in the absence of SSA. Both direct and inverted repeats stimulated excision of the constructs from the attB integration sites independently of HR, NHEJ, or SSA. With episomal constructs, direct and inverted repeats triggered DNA instability by activating nucleolytic activity, and absence of the DSB repair pathways (in the order NHEJ.HR.SSA) exacerbated this instability. Thus, direct and inverted repeats may elicit genetic instability in mycobacteria by 1) directly interfering with replication fidelity, 2) stimulating the three main DSB repair pathways, and 3) enticing L5 site-specific recombination.

Frontiers in Pharmacology, Nov 10, 2022

It was recently reported that 4-substituted picolinohydrazonamides carrying hydrophilic cyclic am... more It was recently reported that 4-substituted picolinohydrazonamides carrying hydrophilic cyclic amines, such as morpholine and pyrrolidine, at the end of their thiosemicarbazide chain have potent antimycobacterial activity in vitro at concentrations below 1 μg/ml. Here, two selected compounds, 2,4disubstituted pyridine derivatives 11 and 15, revealed significant bactericidal activity against Mycobacterium tuberculosis localized intracellularly within human macrophages, as well as against biofilm-forming tubercle bacilli. Mutants were selected that were resistant to the investigated compounds at an efficiency similar to that identified in the presence of the first line antituberculosis drug rifampicin. The resistant mutants were viable in the presence of the tested compounds exclusively on solid media. Genomewide sequencing of the mutants selected in the presence of compound 11 revealed the accumulation of nonsynonymous mutations in the mmpR5 gene encoding a transcriptional repressor of the MmpS5-MmpL5 efflux pump, whose upregulation has been associated with bedaquiline resistance. The depletion of MmpR5 in wild-type M. tuberculosis using CRISPR-Cas9 technology increased the resistance of this strain to compound 11. Mass spectrometry-based proteomics (LC-MS/MS) of wild-type tubercle bacilli growing in subinhibitory concentrations of compounds 11 or 15 revealed 15 overproduced proteins not detectable in the control cells, including virulence-related proteins.

World Journal of Microbiology & Biotechnology, 2000

The rate of transformation of ß-sitosterol to 4-androsten-3,17-dione (AD) by Mycobacterium vaccae... more The rate of transformation of ß-sitosterol to 4-androsten-3,17-dione (AD) by Mycobacterium vaccae increased considerably in the presence of D,L-norleucine and m-fluorophenylalanine. These compounds inhibit the biosynthesis of the complex lipids in the cell wall outermost layer. Non-covalently linked (free) lipids were extracted from control and inhibitor-treated cells, and the fatty acid patterns were determined in the neutral lipid, glycolipid and

Polycations increase the permeability of Mycobacterium vaccae cell envelopes to hydrophobic compo... more Polycations increase the permeability of Mycobacterium vaccae cell envelopes to hydrophobic compounds

Journal of Computational Chemistry, 2012

The use of the MM2QM tool in a combined docking + molecular dynamics (MD) + molecular mechanics (... more The use of the MM2QM tool in a combined docking + molecular dynamics (MD) + molecular mechanics (MM) + quantum mechanical (QM) binding affinity prediction study is presented, and the tool itself is discussed. The system of interest is Mycobacterium tuberculosis (MTB) pantothenate synthetase in complexes with three highly similar sulfonamide inhibitors, for which crystal structures are available. Starting from the structure of MTB pantothenate synthetase in the "open" conformation and following the combined docking + MD + MM + QM procedure, we were able to capture the closing of the enzyme binding pocket and to reproduce the position of the ligands with an average root mean square deviation of 1.6 Å. Protein-ligand interaction energies were reproduced with an average error lower than 10%. The discussion on the MD part and a protein flexibility importance is carried out. The presented approach may be useful especially for finding analog inhibitors or improving drug candidates.

Antimicrobial Agents and Chemotherapy, 2013

ABSTRACTMycobacteria contain genes for several DNA-dependent RNA primases, includingdnaG, which e... more ABSTRACTMycobacteria contain genes for several DNA-dependent RNA primases, includingdnaG, which encodes an essential replication enzyme that has been proposed as a target for antituberculosis compounds. Anin silicoanalysis revealed that mycobacteria also possess archaeo-eukaryotic superfamily primases (AEPs) of unknown function. Using a homologous recombination system, we obtained direct evidence that wild-typednaGcannot be deleted from the chromosome ofMycobacterium smegmatiswithout disrupting viability, even in backgrounds in which mycobacterial AEPs are overexpressed. In contrast, single-deletion AEP mutants or mutants defective for all four identifiedM. smegmatisAEP genes did not exhibit growth defects under standard laboratory conditions. Deletion of nativednaGinM. smegmatiswas tolerated only after the integration of an extra intact copy of theM. smegmatisorMycobacterium tuberculosisdnaGgene, under the control of chemically inducible promoters, into theattBsite of the chromosom...

Microbiology, 2005

The catabolic potential for sterol degradation of fast-growing mycobacteria is well known. Howeve... more The catabolic potential for sterol degradation of fast-growing mycobacteria is well known. However, no genes or enzymes responsible for the steroid degradation process have been identified as yet in these species. One of the key enzymes required for degradation of the steroid ring structure is 3-ketosteroid Δ1-dehydrogenase (KsdD). The recent annotation of the Mycobacterium smegmatis genome (TIGR database) revealed six KsdD homologues. Targeted disruption of the MSMEG5898 (ksdD-1) gene, but not the MSMEG4855 (ksdD-2) gene, resulted in partial inactivation of the cholesterol degradation pathway and accumulation of the intermediate 4-androstene-3,17-dione. This effect was reversible by the introduction of the wild-type ksdD-1 gene into M. smegmatis ΔksdD-1 or overexpression of ksdD-2. The data indicate that KsdD1 is the main KsdD in M. smegmatis, but that KsdD2 is able to perform the cholesterol degradation process when overproduced.

International Journal of Antimicrobial Agents, 2007

The sequence of the human mitochondrial genome was established almost 25 years ago and has been u... more The sequence of the human mitochondrial genome was established almost 25 years ago and has been used in analysis of human population migrations, forensic medicine, longevity studies and in investigation of the causes of mitochondrial diseases.It is a small compact genome of 16.5 kb containing information about 13 protens, 2 rRNAs and 22 tRNAs.There are many variants (haplogroups) of the human mitochondrial genomeand some of them have been associated — for some populations — with longevity orcertain mitochondrial disease. Many of these associations were only detected for certain populations. I will discuss the mitochondrial DNA haplogroups in the Polishpopulation and the association of certain mitohcondrial haplogroups with a mitochondrial blindness, Leber Hereditaty Optic Neuropahy.

Cells, 2020

We have recently found that selected thio-disaccharides possess bactericidal effects against Myco... more We have recently found that selected thio-disaccharides possess bactericidal effects against Mycobacterium tuberculosis but not against Escherichia coli or Staphylococcus aureus. Here, we selected spontaneous mutants displaying resistance against the investigated thio-glycoside. According to next-generation sequencing, four of six analyzed mutants which were resistant to high concentrations of the tested chemical carried nonsynonymous mutations in the gene encoding the PPE51 protein. The complementation of these mutants with an intact ppe51 gene returned their sensitivity to the wild-type level. The uptake of tritiated thio-glycoside was significantly more abundant in wild-type Mycobacterium tuberculosis compared to the strain carrying the mutated ppe51 gene. The ppe51 mutations or CRISPR-Cas9-mediated downregulation of PPE51 expression affected the growth of mutant strains on minimal media supplemented with disaccharides (maltose or lactose) but not with glycerol or glucose as the ...

Genes, 2020

ATP-binding cassette sub-family G member 2 (ABCG2), also known as breast cancer resistance protei... more ATP-binding cassette sub-family G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is one of the key efflux ATP-binding cassette (ABC) transporters of xenobiotics, their metabolites and endogenous compounds such as urate. Some of its genetic variants have been found to influence protein functioning, resulting in serious clinical implications concerning chemotherapy response, as well as gout or blood group phenotype Jr(a-). Previous reports have suggested that the frequencies of certain crucial polymorphisms, such as c.34G>A (p.Val12Met) and c.421C>A (p.Gln141Lys) differ significantly between the Polish population and other Caucasian populations. Thus, to clarify this issue, the present study performs a complete analysis of the genetic variation of ABCG2 coding sequence in the Polish population. The genetic variation in 14 out of 15 coding exons of the ABCG2 gene, as well as their flanking intron sequences, were examined among 190 healthy representatives...

Current Topics in Medicinal Chemistry, 2017

Background: Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is... more Background: Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is a leading infectious disease organism, causing millions of deaths each year. This serious pathogen has been greatly spread worldwide and recent years have observed an increase in the number of multi-drug resistant and totally drug resistant M. tuberculosis strains (WHO report, 2014). The danger of tuberculosis becoming an incurable disease has emphasized the need for the discovery of a new generation of antimicrobial agents. The development of novel alternative medical strategies, new drugs and the search for optimal drug targets are top priority areas of tuberculosis research. Factors: Key characteristics of mycobacteria include: slow growth, the ability to transform into a metabolically silent - latent state, intrinsic drug resistance and the relatively rapid development of acquired drug resistance. These factors make finding an ideal antituberculosis drug enormously challenging, even...

FEMS Microbiology Letters, 2006

Mycobacterium smegmatis was used to study the relationship between DNA repair processes involving... more Mycobacterium smegmatis was used to study the relationship between DNA repair processes involving RecA and nonhomologous end joining (NHEJ). The effect of gene deletions in recA and/or in two genes involved in NHEJ (ku and ligD) was tested on the ability of bacteria to join breaks in plasmids transformed into them and in their response to chemicals that damage DNA. The results provide in vivo evidence that only NHEJ is required for the repair of noncompatible DNA ends. By contrast, the response of mycobacteria to mitomycin C preferentially involved a RecA-dependent pathway.

Acta microbiologica Polonica, 2001

Mycobacterium vaccae exposed to compounds which are known to disorganise the cell wall compositio... more Mycobacterium vaccae exposed to compounds which are known to disorganise the cell wall composition and architecture (protamine, glycine) showed increased specific activity in beta-sitosterol biotransformation to androstene derivatives, intennediates in the production of most medical steroids. GC/MS analysis of free lipid fatty acids revealed higher content of unsaturated compounds, mainly C16:1 and C18:1 in protamine- and glycine-treated cells than that in control cells, which seems to change the permeability features of the cell wall barrier, facilitating hydrophobic beta-sitosterol diffusion.

Bioorganic Chemistry, Dec 31, 2023

Antimicrobial Agents and Chemotherapy, Aug 1, 2007

Mycobacteria contain genes for several DNA ligases, including ligA, which encodes a NAD ؉-depende... more Mycobacteria contain genes for several DNA ligases, including ligA, which encodes a NAD ؉-dependent enzyme that has been postulated to be a target for novel antibacterial compounds. Using a homologous recombination system, direct evidence is presented that wild-type ligA cannot be deleted from the chromosome of Mycobacterium smegmatis. Deletions of native ligA in M. smegmatis could be obtained only after the integration of an extra copy of M. smegmatis or Mycobacterium tuberculosis ligA into the attB site of the chromosome, with expression controlled by chemically inducible promoters. The four ATP-dependent DNA ligases encoded by the M. smegmatis chromosome were unable to replace the function of LigA. Interestingly, the LigA protein from M. smegmatis could be substituted with the NAD ؉-dependent DNA ligase of Escherichia coli or the ATP-dependent ligase of bacteriophage T4. The conditional mutant strains allowed the analysis of the effect of LigA depletion on the growth of M. smegmatis. The protein level of the conditional mutants was estimated by Western blot analysis using antibodies raised against LigA of M. tuberculosis. This revealed that a strong overproduction or depletion of LigA did not affect the growth or survival of mycobacteria under standard laboratory conditions. In conclusion, although NAD ؉-dependent DNA ligase is essential for mycobacterial viability, only low levels of protein are required for growth. These findings suggest that very efficient inhibition of enzyme activity would be required if NAD ؉-dependent DNA ligase is to be useful as an antibiotic target in mycobacteria. The strains developed here will provide useful tools for the evaluation of the efficacy of any appropriate compounds in mycobacteria.

PLoS ONE, 2012

Repetitive DNA sequences with the potential to form alternative DNA conformations, such as slippe... more Repetitive DNA sequences with the potential to form alternative DNA conformations, such as slipped structures and cruciforms, can induce genetic instability by promoting replication errors and by serving as a substrate for DNA repair proteins, which may lead to DNA double-strand breaks (DSBs). However, the contribution of each of the DSB repair pathways, homologous recombination (HR), non-homologous end-joining (NHEJ) and single-strand annealing (SSA), to this sort of genetic instability is not fully understood. Herein, we assessed the genome-wide distribution of repetitive DNA sequences in the Mycobacterium smegmatis, Mycobacterium tuberculosis and Escherichia coli genomes, and determined the types and frequencies of genetic instability induced by direct and inverted repeats, both in the presence and in the absence of HR, NHEJ, and SSA. All three genomes are strongly enriched in direct repeats and modestly enriched in inverted repeats. When using chromosomally integrated constructs in M. smegmatis, direct repeats induced the perfect deletion of their intervening sequences ,1,000-fold above background. Absence of HR further enhanced these perfect deletions, whereas absence of NHEJ or SSA had no influence, suggesting compromised replication fidelity. In contrast, inverted repeats induced perfect deletions only in the absence of SSA. Both direct and inverted repeats stimulated excision of the constructs from the attB integration sites independently of HR, NHEJ, or SSA. With episomal constructs, direct and inverted repeats triggered DNA instability by activating nucleolytic activity, and absence of the DSB repair pathways (in the order NHEJ.HR.SSA) exacerbated this instability. Thus, direct and inverted repeats may elicit genetic instability in mycobacteria by 1) directly interfering with replication fidelity, 2) stimulating the three main DSB repair pathways, and 3) enticing L5 site-specific recombination.

Frontiers in Pharmacology, Nov 10, 2022

It was recently reported that 4-substituted picolinohydrazonamides carrying hydrophilic cyclic am... more It was recently reported that 4-substituted picolinohydrazonamides carrying hydrophilic cyclic amines, such as morpholine and pyrrolidine, at the end of their thiosemicarbazide chain have potent antimycobacterial activity in vitro at concentrations below 1 μg/ml. Here, two selected compounds, 2,4disubstituted pyridine derivatives 11 and 15, revealed significant bactericidal activity against Mycobacterium tuberculosis localized intracellularly within human macrophages, as well as against biofilm-forming tubercle bacilli. Mutants were selected that were resistant to the investigated compounds at an efficiency similar to that identified in the presence of the first line antituberculosis drug rifampicin. The resistant mutants were viable in the presence of the tested compounds exclusively on solid media. Genomewide sequencing of the mutants selected in the presence of compound 11 revealed the accumulation of nonsynonymous mutations in the mmpR5 gene encoding a transcriptional repressor of the MmpS5-MmpL5 efflux pump, whose upregulation has been associated with bedaquiline resistance. The depletion of MmpR5 in wild-type M. tuberculosis using CRISPR-Cas9 technology increased the resistance of this strain to compound 11. Mass spectrometry-based proteomics (LC-MS/MS) of wild-type tubercle bacilli growing in subinhibitory concentrations of compounds 11 or 15 revealed 15 overproduced proteins not detectable in the control cells, including virulence-related proteins.

World Journal of Microbiology & Biotechnology, 2000

The rate of transformation of ß-sitosterol to 4-androsten-3,17-dione (AD) by Mycobacterium vaccae... more The rate of transformation of ß-sitosterol to 4-androsten-3,17-dione (AD) by Mycobacterium vaccae increased considerably in the presence of D,L-norleucine and m-fluorophenylalanine. These compounds inhibit the biosynthesis of the complex lipids in the cell wall outermost layer. Non-covalently linked (free) lipids were extracted from control and inhibitor-treated cells, and the fatty acid patterns were determined in the neutral lipid, glycolipid and

Polycations increase the permeability of Mycobacterium vaccae cell envelopes to hydrophobic compo... more Polycations increase the permeability of Mycobacterium vaccae cell envelopes to hydrophobic compounds

Journal of Computational Chemistry, 2012

The use of the MM2QM tool in a combined docking + molecular dynamics (MD) + molecular mechanics (... more The use of the MM2QM tool in a combined docking + molecular dynamics (MD) + molecular mechanics (MM) + quantum mechanical (QM) binding affinity prediction study is presented, and the tool itself is discussed. The system of interest is Mycobacterium tuberculosis (MTB) pantothenate synthetase in complexes with three highly similar sulfonamide inhibitors, for which crystal structures are available. Starting from the structure of MTB pantothenate synthetase in the "open" conformation and following the combined docking + MD + MM + QM procedure, we were able to capture the closing of the enzyme binding pocket and to reproduce the position of the ligands with an average root mean square deviation of 1.6 Å. Protein-ligand interaction energies were reproduced with an average error lower than 10%. The discussion on the MD part and a protein flexibility importance is carried out. The presented approach may be useful especially for finding analog inhibitors or improving drug candidates.

Antimicrobial Agents and Chemotherapy, 2013

ABSTRACTMycobacteria contain genes for several DNA-dependent RNA primases, includingdnaG, which e... more ABSTRACTMycobacteria contain genes for several DNA-dependent RNA primases, includingdnaG, which encodes an essential replication enzyme that has been proposed as a target for antituberculosis compounds. Anin silicoanalysis revealed that mycobacteria also possess archaeo-eukaryotic superfamily primases (AEPs) of unknown function. Using a homologous recombination system, we obtained direct evidence that wild-typednaGcannot be deleted from the chromosome ofMycobacterium smegmatiswithout disrupting viability, even in backgrounds in which mycobacterial AEPs are overexpressed. In contrast, single-deletion AEP mutants or mutants defective for all four identifiedM. smegmatisAEP genes did not exhibit growth defects under standard laboratory conditions. Deletion of nativednaGinM. smegmatiswas tolerated only after the integration of an extra intact copy of theM. smegmatisorMycobacterium tuberculosisdnaGgene, under the control of chemically inducible promoters, into theattBsite of the chromosom...

Microbiology, 2005

The catabolic potential for sterol degradation of fast-growing mycobacteria is well known. Howeve... more The catabolic potential for sterol degradation of fast-growing mycobacteria is well known. However, no genes or enzymes responsible for the steroid degradation process have been identified as yet in these species. One of the key enzymes required for degradation of the steroid ring structure is 3-ketosteroid Δ1-dehydrogenase (KsdD). The recent annotation of the Mycobacterium smegmatis genome (TIGR database) revealed six KsdD homologues. Targeted disruption of the MSMEG5898 (ksdD-1) gene, but not the MSMEG4855 (ksdD-2) gene, resulted in partial inactivation of the cholesterol degradation pathway and accumulation of the intermediate 4-androstene-3,17-dione. This effect was reversible by the introduction of the wild-type ksdD-1 gene into M. smegmatis ΔksdD-1 or overexpression of ksdD-2. The data indicate that KsdD1 is the main KsdD in M. smegmatis, but that KsdD2 is able to perform the cholesterol degradation process when overproduced.

International Journal of Antimicrobial Agents, 2007

The sequence of the human mitochondrial genome was established almost 25 years ago and has been u... more The sequence of the human mitochondrial genome was established almost 25 years ago and has been used in analysis of human population migrations, forensic medicine, longevity studies and in investigation of the causes of mitochondrial diseases.It is a small compact genome of 16.5 kb containing information about 13 protens, 2 rRNAs and 22 tRNAs.There are many variants (haplogroups) of the human mitochondrial genomeand some of them have been associated — for some populations — with longevity orcertain mitochondrial disease. Many of these associations were only detected for certain populations. I will discuss the mitochondrial DNA haplogroups in the Polishpopulation and the association of certain mitohcondrial haplogroups with a mitochondrial blindness, Leber Hereditaty Optic Neuropahy.

Cells, 2020

We have recently found that selected thio-disaccharides possess bactericidal effects against Myco... more We have recently found that selected thio-disaccharides possess bactericidal effects against Mycobacterium tuberculosis but not against Escherichia coli or Staphylococcus aureus. Here, we selected spontaneous mutants displaying resistance against the investigated thio-glycoside. According to next-generation sequencing, four of six analyzed mutants which were resistant to high concentrations of the tested chemical carried nonsynonymous mutations in the gene encoding the PPE51 protein. The complementation of these mutants with an intact ppe51 gene returned their sensitivity to the wild-type level. The uptake of tritiated thio-glycoside was significantly more abundant in wild-type Mycobacterium tuberculosis compared to the strain carrying the mutated ppe51 gene. The ppe51 mutations or CRISPR-Cas9-mediated downregulation of PPE51 expression affected the growth of mutant strains on minimal media supplemented with disaccharides (maltose or lactose) but not with glycerol or glucose as the ...

Genes, 2020

ATP-binding cassette sub-family G member 2 (ABCG2), also known as breast cancer resistance protei... more ATP-binding cassette sub-family G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is one of the key efflux ATP-binding cassette (ABC) transporters of xenobiotics, their metabolites and endogenous compounds such as urate. Some of its genetic variants have been found to influence protein functioning, resulting in serious clinical implications concerning chemotherapy response, as well as gout or blood group phenotype Jr(a-). Previous reports have suggested that the frequencies of certain crucial polymorphisms, such as c.34G>A (p.Val12Met) and c.421C>A (p.Gln141Lys) differ significantly between the Polish population and other Caucasian populations. Thus, to clarify this issue, the present study performs a complete analysis of the genetic variation of ABCG2 coding sequence in the Polish population. The genetic variation in 14 out of 15 coding exons of the ABCG2 gene, as well as their flanking intron sequences, were examined among 190 healthy representatives...

Current Topics in Medicinal Chemistry, 2017

Background: Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is... more Background: Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is a leading infectious disease organism, causing millions of deaths each year. This serious pathogen has been greatly spread worldwide and recent years have observed an increase in the number of multi-drug resistant and totally drug resistant M. tuberculosis strains (WHO report, 2014). The danger of tuberculosis becoming an incurable disease has emphasized the need for the discovery of a new generation of antimicrobial agents. The development of novel alternative medical strategies, new drugs and the search for optimal drug targets are top priority areas of tuberculosis research. Factors: Key characteristics of mycobacteria include: slow growth, the ability to transform into a metabolically silent - latent state, intrinsic drug resistance and the relatively rapid development of acquired drug resistance. These factors make finding an ideal antituberculosis drug enormously challenging, even...

FEMS Microbiology Letters, 2006

Mycobacterium smegmatis was used to study the relationship between DNA repair processes involving... more Mycobacterium smegmatis was used to study the relationship between DNA repair processes involving RecA and nonhomologous end joining (NHEJ). The effect of gene deletions in recA and/or in two genes involved in NHEJ (ku and ligD) was tested on the ability of bacteria to join breaks in plasmids transformed into them and in their response to chemicals that damage DNA. The results provide in vivo evidence that only NHEJ is required for the repair of noncompatible DNA ends. By contrast, the response of mycobacteria to mitomycin C preferentially involved a RecA-dependent pathway.

Acta microbiologica Polonica, 2001

Mycobacterium vaccae exposed to compounds which are known to disorganise the cell wall compositio... more Mycobacterium vaccae exposed to compounds which are known to disorganise the cell wall composition and architecture (protamine, glycine) showed increased specific activity in beta-sitosterol biotransformation to androstene derivatives, intennediates in the production of most medical steroids. GC/MS analysis of free lipid fatty acids revealed higher content of unsaturated compounds, mainly C16:1 and C18:1 in protamine- and glycine-treated cells than that in control cells, which seems to change the permeability features of the cell wall barrier, facilitating hydrophobic beta-sitosterol diffusion.