Project description:The widespread presence of antibiotic-resistant bacteria in the environment has been recognized as an important emerging environmental contaminant. Hospital wards, as a special public indoor environment, are of great concern for the risks associated with this emerging environmental contaminant. Pseudomonas aeruginosa, a common nosocomial bacterium, is a contamination risk in the hospital environment due to its drug resistance and transmission of virulence factors. Notably, the antimicrobial peptide-sensing two-component system (TCS) ParRS and CprRS have been implicated in dynorphin-induced signaling, but the underlying Manuscript2 mechanism has remained elusive. In this study, we performed proteomic analysis to systematically investigate the contributions of ParRS and CprRS to P. aeruginosa pathogenesis and dynorphin-induced resistance to polymyxins. Additionally, we characterized the significance of the extracellular sensor domains of ParS and CprS in dynorphin perception. Furthermore, through structural biology, we identified additional TCS sensors with similar extracellular domain conformations, which also directly interacted with dynorphin in vitro. This suggests convergent evolution in different bacterial TCSs for host-derived synthetic peptide signal transmitting. Our findings establish a link between CAMPs resistance associated TCSs and virulence regulation of common nosocomial bacteria. This further illustrates the danger of this emerging contaminant for the environment and humans.
2024-07-04 | PXD043746 | Pride
Project description:Bioenergetic stress potentiates antimicrobial resistance and persistence
Project description:Klebsiella variicola, traditionally considered a plant-associated species, is now recognized as an emerging foodborne and opportunistic pathogen at the human–animal–environment interface. Its ecological versatility, ability to colonize plants and food matrices, and increasing reports of antimicrobial resistance make this bacterium a growing concern for both public health and food safety. As the demand for alternative and clean-label antimicrobial strategies intensifies, essential oils (EOs) have gained attention for their broad biological activities and multi-target mechanisms. Among these, basil (Ocimum basilicum) essential oil (BEO), rich in linalool and phenylpropanoids, exhibits antimicrobial activity primarily through membrane disruption, metabolic interference, and oxidative imbalance. Despite the expanding use of plant-derived antimicrobials, the cellular response of K. variicola to EOs remains largely unexplored. To address this gap, this study employed a label-free quantitative proteomic approach to characterize the global response of K. variicola to a subinhibitory concentration of BEO. Exposure to BEO markedly affected proteins involved in membrane homeostasis, oxidative stress management, and translation processes. The concurrent repression of energy-related pathways and activation of antioxidant defences indicates that BEO imposes multifactorial physiological stress rather than acting through a single inhibitory target. These findings provide the first proteome-level insight into EO action against K. variicola and highlight molecular vulnerabilities that may reduce its persistence in food-processing environments. Overall, this study supports BEO as a promising natural antimicrobial and offers novel mechanistic clues on how emerging Klebsiella species respond to plant-derived stressors.
Project description:Shotgun metagenomic sequencing of nasopharyngeal (NP) samples, from children enrolled in a PCV13-vaccinated South African birth cohort was used to explore strain-level pneumococcal colonization patterns and transmission dynamics, and associated antimicrobial-resistance determinants. NP swabs were collected at two-week intervals from birth through the first year of life from 137 infants. Pneumococcal isolates were serotyped and tested for phenotypic antimicrobial resistance. 196 NP samples from a subset of 23 infants were then selected based on changes in serotype or antimicrobial resistance. DNA was extracted directly from the enriched NP samples and shotgun metagenomic sequencing performed. Reads were assembled and aligned against reference pneumococcal genomes. in silico pneumococcal capsular, multilocus sequence typing, and resistome analyses were performed.