Dataset Information

Comparative Proteomics of Extended-Spectrum Cephalosporin-Resistant Neisseria gonorrhoeae Isolates Demonstrates Altered Protein Synthesis, Metabolism, Substance Transport, and Membrane Permeability.

ABSTRACT: Neisseria gonorrhoeae isolates exhibit resistance to extended-spectrum cephalosporins (ESCs), the last remaining option for first-line empirical monotherapy. Here, we investigated the proteomic profiles of N. gonorrhoeae clinical isolates with ESC-resistance to support exploration of the antimicrobial resistance mechanisms for N. gonorrhoeae. We used comparative iTRAQ quantitative proteomics to investigate differential protein expression of three ESC-resistant N. gonorrhoeae clinical isolates using N. gonorrhoeae ATCC49226 as a reference strain. The expression of 40 proteins was downregulated and expression of 56 proteins was upregulated in all three ESC-resistant N. gonorrhoeae isolates. Proteins with predicted function of translation, ribosomal structure and biogenesis, as well as components of the Type IV secretory systems, were significantly upregulated. Two differentially expressed proteins of ABC transporters were also reported by other teams in proteomics studies of N. gonorrhoeae isolates under antimicrobial stress conditions. Differentially expressed proteins are involved in energy production and metabolism of carbohydrates and amino acids. Our results indicated that amino acid and carbohydrate metabolism, cell membrane structure, interbacterial DNA transfer, and ribosome components might be involved in mediating ESC-resistance in N. gonorrhoeae. These findings facilitate a better understanding of the mechanisms of ESC-resistance in N. gonorrhoeae and provide useful information for identifying novel targets in the development of antimicrobials against N. gonorrhoeae.

SUBMITTER: Diao N

PROVIDER: S-EPMC7042406 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparative Proteomics of Extended-Spectrum Cephalosporin-Resistant Neisseria gonorrhoeae Isolates Demonstrates Altered Protein Synthesis, Metabolism, Substance Transport, and Membrane Permeability.

Diao Nannan N Yan Guoquan G Yang Yang Y Dong Yuan Y Wang Ying Y Gu Weiming W

Frontiers in microbiology 20200219

Neisseria gonorrhoeae isolates exhibit resistance to extended-spectrum cephalosporins (ESCs), the last remaining option for first-line empirical monotherapy. Here, we investigated the proteomic profiles of N. gonorrhoeae clinical isolates with ESC-resistance to support exploration of the antimicrobial resistance mechanisms for N. gonorrhoeae. We used comparative iTRAQ quantitative proteomics to investigate differential protein expression of three ESC-resistant N. gonorrho ...[more]

PMID: 32140142

Similar Datasets

Project description:The emergence of Neisseria gonorrhoeae strains resistant to extended-spectrum cephalosporins (ESCs) is a worldwide concern because this class of antibiotics represents the last empirical treatment option for gonorrhea. The abusive use of antimicrobials may be an essential factor for the emergence of ESC resistance in N. gonorrhoeae. Cephalosporin resistance mechanisms have not been fully clarified. In this study, we mapped mutations in the genome of N. gonorrhoeae isolates after resistance induction with cefixime and explored related metabolic pathways. Six clinical isolates with different antimicrobial susceptibility profiles and genotypes and two gonococcal reference strains (WHO F and WHO Y) were induced with increasing concentrations of cefixime. Antimicrobial susceptibility testing was performed against six antimicrobial agents before and after induction. Clinical isolates were whole-genome sequenced before and after induction, whereas reference strains were sequenced after induction only. Cefixime resistance induction was completed after 138 subcultures. Several metabolic pathways were affected by resistance induction. Five isolates showed SNPs in PBP2. The isolates M111 and M128 (ST1407 with mosaic penA-34.001) acquired one and four novel missense mutations in PBP2, respectively. These isolates exhibited the highest minimum inhibitory concentration (MIC) for cefixime among all clinical isolates. Mutations in genes contributing to ESC resistance and in other genes were also observed. Interestingly, M107 and M110 (ST338) showed no mutations in key determinants of ESC resistance despite having a 127-fold increase in the MIC of cefixime. These findings point to the existence of different mechanisms of acquisition of ESC resistance induced by cefixime exposure. Furthermore, the results reinforce the importance of the gonococcal antimicrobial resistance surveillance program in Brazil, given the changes in treatment protocols made in 2017 and the nationwide prevalence of sequence types that can develop resistance to ESC.

Dataset Information

Comparative Proteomics of Extended-Spectrum Cephalosporin-Resistant Neisseria gonorrhoeae Isolates Demonstrates Altered Protein Synthesis, Metabolism, Substance Transport, and Membrane Permeability.

Publications

Comparative Proteomics of Extended-Spectrum Cephalosporin-Resistant <i>Neisseria gonorrhoeae</i> Isolates Demonstrates Altered Protein Synthesis, Metabolism, Substance Transport, and Membrane Permeability.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets