Tuberculosis (Edinb)
September 2024
As one of the factors affecting the treatment outcomes, drug tolerance in mycobacteriosis has not been paid due attention. Genome-wide association studies on 607 Mycobacterium tuberculosis clinical isolates with phenotypic drug susceptibility test data revealed that a K114N mutation on the rv2820c gene was highly enriched in capreomycin-resistant isolates (32/213, 15.02%).
View Article and Find Full Text PDFEmerg Microbes Infect
December 2024
Although -aminosalicylic acid (PAS) has been used to treat tuberculosis for decades, mechanisms of resistance to this drug in () clinical isolates have not been thoroughly investigated. Previously, we found that decreased methylenetetrahydrofolate reductase (MTHFR) activity of Rv2172c led to increased sensitivity to antifolates in . In this study, we collected the genome-sequencing data of 173 PAS-resistant and 803 PAS-sensitive clinical isolates and analyzed mutations in those 976 isolates.
View Article and Find Full Text PDFAntibiotics (Basel)
December 2023
Tuberculosis remains a serious challenge to human health worldwide. -Aminosalicylic acid (PAS) is an important anti-tuberculosis drug, which requires sequential activation by () dihydropteroate synthase and dihydrofolate synthase (DHFS, FolC). Previous studies showed that loss of function mutations of a thymidylate synthase coding gene caused PAS resistance in , but the mechanism is unclear.
View Article and Find Full Text PDFEscherichia coli serine hydroxymethyltransferase (GlyA) converts serine to glycine, and mutants are auxotrophic for glycine. CycA is a transporter that mediates glycine uptake. Deleting in E.
View Article and Find Full Text PDFTuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the most fatal diseases in the world. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the production of 5-methyltetrahydrofolate (5-CH-THF), which is required for the biosynthesis of methionine in bacteria. Here, we identified Rv2172c as an MTHFR in M.
View Article and Find Full Text PDFAfter several decades of use, trimethoprim (TMP) remains one of the key access antimicrobial drugs listed by the World Health Organization. To circumvent the problem of trimethoprim resistance worldwide, a better understanding of drug-resistance mechanisms is required. In this study, we screened the single-gene knockout library of , and identified and other several genes involved in trimethoprim resistance.
View Article and Find Full Text PDFOwing to the spread of multidrug resistance (MDR) and extensive drug resistance (XDR), there is a pressing need to identify potential targets for the development of more-effective anti-M. tuberculosis (Mtb) drugs. PafA, as the sole Prokaryotic Ubiquitin-like Protein ligase in the Pup-proteasome System (PPS) of Mtb, is an attractive drug target.
View Article and Find Full Text PDFMol Cell Proteomics
December 2017
(Mtb) has evolved multiple strategies to counter the human immune system. The effectors of Mtb play important roles in the interactions with the host. However, because of the lack of highly efficient strategies, there are only a handful of known Mtb effectors, thus hampering our understanding of Mtb pathogenesis.
View Article and Find Full Text PDFMarR family proteins are transcriptional regulators that control expression of bacterial proteins involved in metabolism, virulence, stress responses and multi-drug resistance, mainly via ligand-mediated attenuation of DNA binding. Greater understanding of their underlying regulatory mechanism may open up new avenues for the effective treatment of bacterial infections. To gain molecular insight into the mechanism of Rv2887, a MarR family protein in M.
View Article and Find Full Text PDFAntimicrob Agents Chemother
October 2017
Although the folate biosynthesis pathway has been well studied in bacteria, little is known about its regulation. In the present study, the gene in was deleted. Subsequent drug susceptibility tests revealed that the Δ strain was more sensitive to -aminosalicylic acid (PAS) and sulfamethoxazole.
View Article and Find Full Text PDF(Mtb) is the causative agent of tuberculosis, the leading cause of death among all infectious diseases. There are 11 eukaryotic-like serine/threonine protein kinases (STPKs) in Mtb, which are thought to play pivotal roles in cell growth, signal transduction and pathogenesis. However, their underlying mechanisms of action remain largely uncharacterized.
View Article and Find Full Text PDFAntimicrob Agents Chemother
May 2017
Co-trimoxazole, a fixed-dose combination of sulfamethoxazole (SMX) and trimethoprim (TMP), has been used for the treatment of bacterial infections since the 1960s. Since it has long been assumed that the synergistic effects between SMX and TMP are the consequence of targeting 2 different enzymes of bacterial folate biosynthesis, 2 genes ( and ) involved in the folate biosynthesis of were deleted, and their effects on the susceptibility to antifolates were tested. The results showed that the deletion of resulted in a lag of growth in minimal medium and increased susceptibility to both SMX and TMP.
View Article and Find Full Text PDFJ Antibiot (Tokyo)
March 2017
Synergies between sulfonamides and other antimicrobial agents have long been reported, but the reason still remains unclear. Previously, Vilchèze et al. found that, sulfamethoxazole (SMX) could potentiate the bacterialcidal activity of isoniazid (INH) and rifampin (RIF) in Mycobacterium tuberculosis.
View Article and Find Full Text PDFCore-shell structural adenosine-imprinted microspheres were prepared via a two-step procedure. Polystyrene core particles (CP) were firstly prepared via a reversible addition-fragmentation chain transfer (RAFT) polymerization leaving the iniferter on the surface of the cores, then a molecularly imprinted polymer (MIP) shell was synthesized on the surface of the cores by using acrylamide (AAm) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker. The formation and growth of the MIP layer were seen dependent on the initiator (AIBN), AAm and the polymerization time used within the polymerization.
View Article and Find Full Text PDFGFP-like fluorescent proteins with diverse emission wavelengths have been developed through mutagenesis, offering many possible choices in cellular and tissue imaging, such as multi-targets imaging, deep tissue imaging that require longer emission wavelength. Here, we utilized a combined approach of random mutation and structure-based rational design to develop new NIR fluorescent proteins on the basis of a far-red fluorescent protein, mNeptune (Ex/Em: 600/650 nm). We created a number of new monomeric NIR fluorescent proteins with the emission range of 681-685 nm, which exhibit the largest Stocks shifts (77-80 nm) compared to other fluorescent proteins.
View Article and Find Full Text PDFReversible lysine acetylation is one of the most important protein posttranslational modifications that plays essential roles in both prokaryotes and eukaryotes. However, only a few lysine deacetylases (KDACs) have been identified in prokaryotes, perhaps in part due to their limited sequence homology. Herein, we developed a 'clip-chip' strategy to enable unbiased, activity-based discovery of novel KDACs in the Escherichia coli proteome.
View Article and Find Full Text PDFThe self-assembly of nanoparticles into larger superstructures is a powerful strategy to develop novel functional nanomaterials, as these superstructures display collective properties that are different to those displayed by individual nanoparticles or bulk samples. However, there are increasing bottlenecks in terms of size control and multifunctionalization of nanoparticle assemblies. In this study, we developed a self-assembly strategy for construction of multifunctional nanoparticle assemblies of tunable size, through rational regulation of the number of self-assembling interaction sites on each nanoparticle.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
September 2014
For living deep-tissue imaging, the optical window favorable for light penetration is in near-infrared wavelengths, which requires fluorescent proteins with emission spectra in the near-infrared region. Here, we report that a single mutant Ser28His of mNeptune with a near-infrared (≥650 nm) emission maxima of 652 nm is found to improve the brightness, photostability, and pH stability when compared with its parental protein mNeptune, while it remains as a monomer, demonstrating that there is still plenty of room to improve the performance of the existing near infrared fluorescence proteins by directed evolution.
View Article and Find Full Text PDFThe mechanistic basis for the resistance of Mycobacterium tuberculosis to para-aminosalicylic acid (PAS), an important agent in the treatment of multidrug-resistant tuberculosis, has yet to be fully defined. As a substrate analog of the folate precursor para-aminobenzoic acid, PAS is ultimately bioactivated to hydroxy dihydrofolate, which inhibits dihydrofolate reductase and disrupts the operation of folate-dependent metabolic pathways. As a result, the mutation of dihydrofolate synthase, an enzyme needed for the bioactivation of PAS, causes PAS resistance in M.
View Article and Find Full Text PDFFEMS Microbiol Lett
October 2013
CheY, the response regulator of the chemotaxis system in Escherichia coli, can be regulated by two covalent modifications - phosphorylation and acetylation. Both covalent modifications are involved in chemotaxis, but the mechanism and role of the acetylation are still obscure. While acetylation was shown to repress the binding of CheY to its target proteins, the effect of acetylation on the ability of CheY to undergo autophosphorylate with AcP is not fully investigated.
View Article and Find Full Text PDFViruses encapsulating inorganic nanoparticles are a novel type of nanostructure with applications in biomedicine and biosensors. However, the encapsulation and assembly mechanisms of these hybridized virus-based nanoparticles (VNPs) are still unknown. In this article, it was found that quantum dots (QDs) can induce simian virus 40 (SV40) capsid assembly in dissociation buffer, where viral capsids should be disassembled.
View Article and Find Full Text PDFCobB is a bacterial NAD(+)-dependent protein deacetylase. Although progress has been made in functional studies of this protein in recent years, its substrates and biological functions are still largely unclear. Using proteome microarray technology, potential substrates of Escherichia coli CobB were screened and nine proteins were identified, including N-hydroxyarylamine O-acetyltransferase (NhoA).
View Article and Find Full Text PDFThere is an urgent need for convenient, sensitive, and specific methods to detect the spores of Bacillus anthracis, the causative agent of anthrax, because of the bioterrorism threat posed by this bacterium. In this study, we firstly develop a super-paramagnetic lateral-flow immunological detection system for B. anthracis spores.
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