Project description:Genomic and Transcriptomic Insights into Chlorhexidine Adaptation in Oral Streptococcus spp.: Implications for Antimicrobial Resistance
Project description:Chlorhexidine (CHX) is a widely used antiseptic agent in dental care due to its broad-spectrum antimicrobial properties. This study focuses on the transcriptomic changes associated with chlorhexidine adaptation in oral Streptococcus salivarius (73_wt, 73_a), Streptococcus vestibularis (78_wt, 78_e), and Streptococcus mitis (93_wt, 93_d) using RNA sequencing.
Project description:Shotgun metagenomic sequencing data for nasopharyngeal colonization dynamics with Streptococcus pneumoniae and associated antimicrobial-resistance in a South African birth cohort.
| EGAD00001006244 | EGA
Project description:Genomic, antimicrobial resistance and public health insights into Enterococcus spp. from Australian chickens
Project description:Despite the widespread use of antiseptics such as chlorhexidine digluconate (CHX) in dental practice and oral care, the risks of potential resistance toward antiseptics in oral bacteria have only been highlighted very recently. Since the molecular mechanisms behind antiseptic resistance or adaptation are not entirely clear yet and the bacterial stress response has not been investigated systematically so far, the aim of the present study was to investigate the transcriptomic stress response in Streptococcus mutans after treatment with CHX using RNA sequencing. Planktonic cultures of stationary phase S. mutans were treated with a sublethal dose of CHX (125 µg/mL) for 5 min. After treatment, RNA was extracted, and RNA sequencing was performed on the Illumina NextSeq 500. Differential expressed genes were analyzed and validated by qRT-PCR. The analysis of the differential gene expression following pathway analysis revealed a considerable number of genes and pathways significantly regulated in S. mutans after sublethal treatment with CHX. In summary, expression of 423 genes was up-regulated and 295 genes down-regulated after CHX treatment. Analysis of differentially expressed genes and significantly regulated pathways showed regulation of genes involved in purine nucleotide synthesis, biofilm formation, transport systems and stress responses. In conclusion, these results show an overview of the transcriptomic stress response in S. mutans upon exposure to CHX and give an insight in potential mechanisms that may result in development of resistances.
Project description:Enterococcus faecalis is a Gram-positive bacterium that is a major cause of hospital-acquired infections due to its intrinsic resistance to cell wall-active antimicrobials. One critical determinant of this resistance is the transmembrane kinase IreK, which belongs to the PASTA kinase family of bacterial signaling proteins involved with the regulation of cell wall homeostasis. IreK has enhanced activity in response to cell wall stress, but direct substrates of IreK phosphorylation leading to antimicrobial resistance are largely unknown. To better understand stress-modulated phosphorylation events contributing to virulence, wild type E. faecalis treated with cell wall-active chlorhexidine and ceftriaxone were examined via phosphoproteomics. Among the most prominent changes were increased phosphorylation of divisome components after both treatments, implicating cell division proteins in antimicrobial defense signaling. Phosphorylation mediated by IreK was then determined via similar analysis with a E. faecalis ΔireK mutant strain, revealing potential IreK substrates involved with the formation/maintenance of biofilms and within the E. faecalis two-component system, another common signal transduction pathway for antimicrobial resistance. These results reveal critical insights into the biological functions of IreK and the mechanisms of E. faecalis antimicrobial resistance.
Project description:The increasing resistence and/or bacterial tolerance to bactericides, such as chlorhexidine, causes worrisome public health problems. Using transcriptomical and microbiological studies, we analysed the molecular mechanisms associated with the adaptation to chlorhexidine in two carbapenemase-producing strains of Klebsiella pneumoniae belonging ST258-KPC3 and ST846-OXA48.
Project description:Overuse of cationic biocides including quaternary ammonium compounds (QACs) poses a growing threat by selecting for antimicrobial resistance. Here, we use Streptococcus gordonii, a commensal opportunistic pathogen, as a model to elucidate the mechanisms of QAC lethality and resistance. We show that QACs trigger V-type ATPase–driven metabolic dysfunction, leading to oxidative phosphorylation (OXPHOS) dominance and excessive reactive oxygen species (ROS) accumulation. Resistance arises through synergistic regulation by ClpX and PstB, which repress the competence pathway regulator ComDE and reprogram metabolism toward aerobic glycolysis, thereby limiting ROS production. Mechanistically, ClpX modulates ComDE signaling through protein aggregation and HtrA-mediated degradation of competence-stimulating peptide, while PstB governs ComDE via phosphorylation of the mannose-specific phosphotransferase system. Activation of ComDE restores ROS-mediated QAC lethality, identifying this pathway as a potential therapeutic target. These findings reveal that metabolic adaptation driven by competence regulon governs biocide susceptibility and adaptation, offering new strategies to counteract QAC resistance and associated cross-resistance in commensal bacteria.
