Biomedical subjects

Junping Peng

Publications and source records attributed to Junping Peng.

8 recordsLinked to original sources

PubMed2026

Heterogeneity of azithromycin resistance markers in Neisseria gonorrhoeae and challenges in implementing molecular assays for routine surveillance.

Neisseria gonorrhoeae is the second most prevalent bacterial sexually transmitted infection and a major contributor to the global antimicrobial resistance crisis. The World Health Organization (WHO) has designated N. gonorrhoeae as a high-priority pathogen due to its resistance to nearly all empirically recommended therapies. While dual therapy with ceftriaxone and azithromycin initially demonstrated efficacy, the rapid global rise in azithromycin resistance over the past five years threatens the efficacy of this regimen. Resistance mechanisms, including mutations in the 23S rRNA gene and overexpression of the MtrCDE efflux pump, are highly heterogeneous, complicating molecular diagnostic efforts. This review examines the evolving landscape of azithromycin resistance, highlighting key mechanisms of resistance, and recent epidemiological and genomic surveillance data. We discuss challenges in implementing molecular assays for routine resistance monitoring due to molecular heterogeneity in azithromycin resistance markers and emphasize the critical need for tailored approaches based on local genetic epidemiology. Enhanced surveillance and molecular diagnostics are essential to sustaining effective treatment strategies and combating gonococcal resistance.

Antimicrobial resistance↗

PubMed2006

Transcriptional profiles of the response to ketoconazole and amphotericin B in Trichophyton rubrum.

Trichophyton rubrum is a pathogenic filamentous fungus of increasing medical concern. Two antifungal agents, ketoconazole (KTC) and amphotericin B (AMB), have specific activity against dermatophytes. To identify the mechanisms of action of KTC and AMB against T. rubrum, a cDNA microarray was constructed from the expressed sequence tags of the cDNA library from different developmental stages, and transcriptional profiles of the responses to KTC and AMB were determined. T. rubrum was exposed to subinhibitory concentrations of KTC and AMB for 12 h, and microarray analysis was used to examine gene transcription. KTC exposure induced transcription of genes involved in lipid, fatty acid, and sterol metabolism, including ERG11, ERG3, ERG25, ERG6, ERG26, ERG24, ERG4, CPO, INO1, DW700960, CPR, DW696584, DW406350, and ATG15. KTC also increased transcription of the multidrug resistance gene ABC1. AMB exposure increased transcription of genes involved in lipid, fatty acid, and sterol metabolism (DW696584, EB801458, IVD, DW694010, DW688343, DW684992), membrane transport (Git1, DW706156, DW684040, DMT, DW406136, CCH1, DW710650), and stress-related responses (HSP70, HSP104, GSS, AOX, EB801455, EB801702, TDH1, UBI4) but reduced transcription of genes involved in maintenance of cell wall integrity and signal transduction pathways (FKS1, SUN4, DW699324, GAS1, DW681613, SPS1, DW703091, STE7, DW703091, DW695308) and some ribosomal proteins. This is the first report of the use of microarray analysis to determine the effects of drug action in T. rubrum.

Amphotericin B↗

PubMed2006

The use of comparative genomic hybridization to characterize genome dynamics and diversity among the serotypes of Shigella.

BACKGROUND: Compelling evidence indicates that Shigella species, the etiologic agents of bacillary dysentery, as well as enteroinvasive Escherichia coli, are derived from multiple origins of Escherichia coli and form a single pathovar. To further understand the genome diversity and virulence evolution of Shigella, comparative genomic hybridization microarray analysis was employed to compare the gene content of E. coli K-12 with those of 43 Shigella strains from all lineages. RESULTS: For the 43 strains subjected to CGH microarray analyses, the common backbone of the Shigella genome was estimated to contain more than 1,900 open reading frames (ORFs), with a mean number of 726 undetectable ORFs. The mosaic distribution of absent regions indicated that insertions and/or deletions have led to the highly diversified genomes of pathogenic strains. CONCLUSION: These results support the hypothesis that by gain and loss of functions, Shigella species became successful human pathogens through convergent evolution from diverse genomic backgrounds. Moreover, we also found many specific differences between different lineages, providing a window into understanding bacterial speciation and taxonomic relationships.

DNA, Bacterial↗

PubMed2006

Complete genome sequence of Shigella flexneri 5b and comparison with Shigella flexneri 2a.

BACKGROUND: Shigella bacteria cause dysentery, which remains a significant threat to public health. Shigella flexneri is the most common species in both developing and developed countries. Five Shigella genomes have been sequenced, revealing dynamic and diverse features. To investigate the intra-species diversity of S. flexneri genomes further, we have sequenced the complete genome of S. flexneri 5b strain 8401 (abbreviated Sf8401) and compared it with S. flexneri 2a (Sf301). RESULTS: The Sf8401 chromosome is 4.5-Mb in size, a little smaller than that of Sf301, mainly because the former lacks the SHI-1 pathogenicity island (PAI). Compared with Sf301, there are 6 inversions and one translocation in Sf8401, which are probably mediated by insertion sequences (IS). There are clear differences in the known PAIs between these two genomes. The bacteriophage SfV segment remaining in SHI-O of Sf8401 is clearly larger than the remnants of bacteriophage SfII in Sf301. SHI-1 is absent from Sf8401 but a specific related protein is found next to the pheV locus. SHI-2 is involved in one intra-replichore inversion near the origin of replication, which may change the expression of iut/iuc genes. Moreover, genes related to the glycine-betaine biosynthesis pathway are present only in Sf8401 among the known Shigella genomes. CONCLUSION: Our data show that the two S. flexneri genomes are very similar, which suggests a high level of structural and functional conservation between the two serotypes. The differences reflect different selection pressures during evolution. The ancestor of S. flexneri probably acquired SHI-1 and SHI-2 before SHI-O was integrated and the serotypes diverged. SHI-1 was subsequently deleted from the S. flexneri 5b genome by recombination, but stabilized in the S. flexneri 2a genome. These events may have contributed to the differences in pathogenicity and epidemicity between the two serotypes of S. flexneri.

Chromosome Aberrations↗

PubMed2006

Genomic compositions and phylogenetic analysis of Shigella boydii subgroup.

Comparative Genomic Hybridization (CGH) microarray analysis was used to compare the genomic compositions of all eighteen Shigella boydii serotype representative strains. The results indicated the genomic "backbone" of this subgroup contained 2552 ORFs homologous to nonpathogenic E. coli K12. Compared with the genome of K12199 ORFs were found to be absent in all S. boydii serotype representatives, including mainly outer membrane protein genes and O-antigen biosynthesis genes. Yet the specific ORFs of S. boydii subgroup contained basically bacteriophage genes and the function unknown (FUN) genes. Some iron metabolism, transport and type II secretion system related genes were found in most representative strains. According to the CGH phylogenetic analysis, the eighteen S. boydii serotype representatives were divided into four groups, in which serotype C13 strain was remarkably distinguished from the other serotype strains. This grouping result corresponded to the distribution of some metabolism related genes. Furthermore, the analysis of genome backbone genes, specific genes, and the phylogenetic trees allowed us to discover the evolution laws of S. boydii and to find out important clues to pathogenesis research, vaccination and the therapeutic medicine development.

Gene Deletion↗

PubMed2006

Construction, detection and microarray analysis on Shigella dysenteriae a1 IroN, ShuA single, double mutants.

In this study, we constructed single mutants MTS-1, MTS-2 of IroN and ShuA gene and double mutant MTS of them in Shigella dysenteriae A1 strain 51197 by insert and absence. The functional detection of every mutant was performed at the level of culture medium and cell experiment. The gene expression profiles of the mutants and the wild-type strains under iron-enriched and iron-limited conditions were analyzed by the SD51197 whole genomic microarray. The results showed that all the mutants grew obviously less well than the wild-type strains in L broth appending iron chelator DIP. The addition of iron to the cultures can stimulate the growth of mutants back to wild-type levels. In either the experiments on the ability of intracellular multiplication or the cell-to-cell spread in HeLa and U937 cell lines, mutants showed no obvious change in virulence compared with the parental strain SD51197. However when DIP was added to the cultured HeLa cells, the ability of intracellular multiplication of MTS-1, MTS-2, MTS has reduced about 23.4%, 25.2%, 43.6% respectively. The analysis of expression profiles under the iron-limited condition showed that the mutants were more sensitive for the changes of iron deficiency than the wild-type strains, many genes have been altered. Up-regulated genes mainly involved genes of transcription, coenzyme metabolism, amino acid transport and metabolism, and unknown functional genes, while down-regulated genes mainly involved genes of energy and carbohydrate metabolism and unknown function genes; the expression levels of known iron-transport associated genes generally showed up-regulated. The results demonstrated that iron-transport associated genes IroN, ShuA were likely to have some effects on the virulence and growth of S. dysenteriae.

Cell Line↗

PubMed2005

Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery.

The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately 700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features.

DNA Transposable Elements↗

PubMed2005

Comparative genomics and phylogenetic analysis of S. dysenteriae subgroup.

Genomic compositions of representatives of thirteen S. dysenteriae serotypes were investigated by performing comparative genomic hybridization (CGH) with microarray containing the whole genomic ORFs (open reading frames, ORFs) of E. coli K12 strain MG1655 and specific ORFs of S. dysenteriae A1 strain Sd51197. The CGH results indicated the genomes of the serotypes contain 2654 conserved ORFs originating from E. coli. However, 219 intrinsic genes of E. coli including those prophage genes, molecular chaperones, synthesis of specific O antigen and so on were absent. Moreover, some specific genes such as type II secretion system associated components, iron transport related genes and some others as well were acquired through horizontal transfer. According to phylogenic trees based on genetic composition, it was demonstrated that A1, A2, A8, A10 were distinct from the other S. dysenteriae serotypes. Our results in this report may provide new insights into the physiological process, pathogenicity and evolution of S. dysenteriae.

Genes, Bacterial↗