Bacterial resistance caused by the abuse of antimicrobial drugs has been a global crisis. There is an urgent need to develop rapid and sensitive diagnostic methods to detect pathogenic bacteria in clinical samples. Bacterial infection-specific molecular probes combined with medical molecular imaging technology provide new ideas for rapid and accurate diagnosis of bacterial infections in vivo and in vitro. However, molecular probes and imaging methods that can label pathogens with high specificity in a complex biological environment are still limited. Recently, Hu Haiyu's research group from the Institute of Materia Medica, Chinese Academy of Medical Sciences and Lei Xiaoguang's research group from the School of Chemistry and Molecular Engineering of Peking University have developed a new fluorescent probe based on theTrojan horse strategy, which first makes the diagnosis of Pseudomonas aeruginosa (P. aeruginosa) in a complex biological environment come true, providing a visual tool for rapid and accurate diagnosis of P. aeruginosain vivo and in vitro as well as the guidance of clinical medication. The research titled A pseudopaline fluorescent probe for the selective detection of Pseudomonas aeruginosa was published in the Chinese Chemical Society Chemistry (CCS Chemistry) on October 19, 2020.
P. aeruginosais a common pathogen of nosocomial infections, which causes high morbidity and mortality in patients, notably in immuno-compromised patients. The outer membrane of P. aeruginosa has low permeability and is naturally resistant to many clinical antibiotics (such as ampicillin, amoxicillin, vancomycin, etc.), and is a veritable “super bacterium”. Pseudopaline, a unique metallophore produced by P. aeruginosa, transports divalent metal ions via a metal transport system, making it an ideal carrier for a second functional moiety.
In 2019, Lei Xiaoguang's research group first realized the total chemical synthesis of Pseudopaline (Chem. Sci., 2019, 10, 6635–6641), combining the advantages of Hu Haiyu's research group in the field of bacterial infection-specific molecular probes and imaging technology, they cooperated developing a series of new pseudopaline-fluorescent probes, which can achieve specific labeling of P. aeruginosa in mammalian cells and tissue sections in a multi-bacterial mixed environment, providing new thoughts in rapid and accurate detection of P. aeruginosa infection. The further developed pseudopaline-Cy7 near-infrared fluorescent probe was first applied in high-specific in vivo diagnosis and localization of P. aeruginosa infection in the mouse model, the results of which are not affected by other pathogens or intestinal flora. The work provides new tools for the specific diagnosis of P. aeruginosa, clinical guidance of medication, clarification of bacterial metal metabolism pathways, and discovery of new antibiotic drugs.
