Transcriptomic Profiling of Ceftriaxone Tolerant- Phenotypes of <i>Neisseria gonorrhoeae</i> Reveals Downregulation of Ribosomal Genes

• DOI: 10.20944/preprints202503.1648.v1
• Publication Date: 2025-03-26T05:23:44Z
• Authors: Sheeba Manoharan-...; Margaux Balduck; Zina Gestels; Said Abdelatti; Tessa de Block; Chris Kenyon
• Keywords: Neisseria gonorrhoeae

Background Antibiotic tolerance is associated with failure of antibiotic treatment and accelerates the development antimicrobial resistance. The molecular mechanisms underlying remain, poorly understood. In some instances, tolerant bacteria can slow metabolism by extending lag phase without altering susceptibility. We recently induced ceftriaxone (CRO) in N. gonorrhoeae reference strain WHO P. current study, we characterized transcriptomic profiles these CRO-tolerant phenotypes. Methods To induce tolerance, P strains were grown under three-hour intermittent CRO exposure (10× MIC), followed overnight growth GC broth for seven consecutive days, cultures maintained sextuplicate. Two control exposure. susceptibility isolates assessed using a modified Tolerance Disc (TD) test. Total RNA was isolated from (n=12) (n = 3) strains, Ribo depletion. Library preparation carried out Stranded TruSeq library kit. Sequencing performed on NextSeq6000, v2. 1 × 150 bp (Illumina Inc., San Diego, CA, USA), data analysis CLC Genomics Workbench v22 (clcbio, Denmark). Results Transcriptomic revealed no differentially expressed genes at first time point that (after day exposure). However, after 3 days exposure, 13 found to be significantly downregulated, including tRNA-Ser (C7S06_RS03100) tRNA-Leu (C7S06_RS04945) ribosomal (16S 23S rRNA). Following 7 51 most such as SecB (Protein-export chaperone SecB) (C7S06_RS01850) 16S genes. Conclusions CRO-tolerance downregulation various genes, reflecting potential mechanism bacterial survival stress.