Lusutrombopag as a Repurposing Drug in Combination with Aminoglycosides against Vancomycin-Resistant Enterococcus.

Due to the widespread abuse of antibiotics, drug resistance in Enterococcus has been increasing. However, the speed of antibiotic discovery cannot keep pace with the acquisition of bacterial resistance. Thus, drug repurposing is a proposed strategy to solve the crises. Lusutrombopag (LP) has been approved as a thrombopoietin receptor agonist by the Food and Drug Administration. This study demonstrated that LP exhibited significant antimicrobial activities against vancomycin-resistant Enterococcus in vitro with rare resistance occurrence. Further, LP combined with tobramycin exhibited synergistic antimicrobial effects in vitro and in vivo against Enterococcus. No in vitro or in vivo detectable toxicity was observed when using LP. Mechanism studies indicated that the disrupted proton motive force may account for LP's antimicrobial activity. In summary, these results demonstrate that LP has the previously undocumented potential to serve as an antibacterial agent against refractory infections caused by Enterococcus.

Repurposing of the antimalarial agent tafenoquine to combat MRSA.

IMPORTANCE: This study represents the first investigation into the antimicrobial effect of TAF against S. aureus and its potential mechanisms. Our data highlighted the effects of TAF against MRSA planktonic cells, biofilms, and persister cells, which is conducive to broadening the application of TAF. Through mechanistic studies, we revealed that TAF targets bacterial cell membranes. In addition, the in vivo experiments in mice demonstrated the safety and antimicrobial efficacy of TAF, suggesting that TAF could be a potential antibacterial drug candidate for the treatment of infections caused by multiple drug-resistant S. aureus.

Inotodiol ameliorates the progression of osteoarthritis: An in vitro and in vivo study.

Osteoarthritis is a common chronic degenerative disease, of which the essence is the degenerative changes of bone and joint cartilage, involving damage in multiple structures such as bone, synovium and joints. In the mechanism of arthritis inflammation is closely related, and therefore the exploration to inhibit inflammatory mediators is crucial for the clinical prevention and treatment of osteoarthritis. Inotodiol is a lanostane triterpenoid isolated from Inonotus obliquus, which had been extensively reported to be an anti-inflammatory agent, but its effect on arthritis remains unknown. In this study, we firstly demonstrated that inotodiol significantly reduced IL-1ß-induced chondrocyte injury and inhibited the release of inflammatory factors. At the same time, experiments in vivo showed that inotodiol could effectively improve the symptoms of joint injury in mice and reduce the area of cartilage destruction, indicating that inotodiol may be a potential therapeutic drug for osteoarthritis.

Disturbed hippocampal histidine metabolism contributes to cognitive impairment induced by recurrent nonsevere hypoglycemia in diabetes.

Hypoglycemia is a common adverse reaction to glucose-lowering treatment. Diabetes mellitus (DM) combined with recurrent nonsevere hypoglycemia (RH) can accelerate cognitive decline. Currently, the metabolic pattern changes in cognition-related brain regions caused by this combined effect of DM and RH (DR) remain unclear. In this study, we first characterized the metabolic profiles of the hippocampus in mice exposed to DR using non-targeted metabolomic platforms. Our results showed that DR induced a unique metabolic pattern in the hippocampus, and several significant differences in metabolite levels belonging to the histidine metabolism pathway were discovered. Based on these findings, in the follow-up experiment, we found that histidine treatment could attenuate the cognitive impairment and rescue the neuronal and synaptic damage induced by DR in the hippocampus, which are closely related to ameliorated mitochondrial injury. These findings provide new insights into the metabolic mechanisms of the hippocampus in the progression of DR, and l-histidine supplementation may be a potential metabolic therapy in the future.

Effects of prebiotics on the gut microbiota in vitro associated with functional diarrhea in children.

Purpose: Diarrhea is among the top five causes of morbidity and mortality in children. Dysbiosis of the gut microbiota is considered the most important risk factor for diarrhea. Prebiotics have shown efficacy in treating diarrhea by regulating the balance of the gut microbiota in vivo. Methods: In this study, we used an in vitro fermentation system to prevent the interference of host-gut microbe interactions during in vivo examination and investigated the effect of fructo-oligosaccharides (FOS) on gut microbiota composition and metabolism in 39 pediatric patients with functional diarrhea. Results: 16S rRNA sequencing revealed that FOS significantly improved α- and ß-diversity in volunteers with pediatric diarrhea (p < 0.05). This improvement manifested as a significant increase (LDA > 2, p < 0.05) in probiotic bacteria (e.g., Bifidobacterium) and a significant inhibition (LDA > 2, p < 0.05) of harmful bacteria (e.g., Escherichia-Shigella). Notably, the analysis of bacterial metabolites after FOS treatment showed that the decrease in isobutyric acid, isovaleric acid, NH3, and H2S levels was positively correlated with the relative abundance of Lachnoclostridium. This decrease also showed the greatest negative correlation with the abundance of Streptococcus. Random forest analysis and ROC curve validation demonstrated that gut microbiota composition and metabolites were distinct between the FOS treatment and control groups (area under the curve [AUC] > 0.8). Functional prediction using PICRUSt 2 revealed that the FOS-induced alteration of gut microbiota was most likely mediated by effects on starch and sucrose metabolism. Conclusion: This study is the first to evince that FOS can modulate gut microbial disorders in children with functional diarrhea. Our findings provide a framework for the application of FOS to alleviate functional diarrhea in children and reduce the use of antibiotics for managing functional diarrhea-induced disturbances in the gut microbiota.

Application of a novel strong promoter from Chinese fir (Cunninghamia lanceolate) in the CRISPR/Cas mediated genome editing of its protoplasts and transgenesis of rice and poplar.

Novel constitutive promoters are essential for plant biotechnology. Although in angiosperms, a number of promoters were applied in monocots or dicots genetic engineering, only a few promoters were used in gymnosperm. Here we identified two strong promoters (Cula11 and Cula08) from Chinese fir (C. lanceolate) by screening the transcriptomic data and preliminary promoter activity assays in tobacco. By using the newly established Chinese fir protoplast transient expression technology that enables in vivo molecular biology studies in its homologous system, we compared the activities of Cula11 and Cula08 with that of the commonly used promoters in genetic engineering of monocots or dicots, such as CaM35S, CmYLCV, and ZmUbi, and our results revealed that Cula11 and Cula08 promoters have stronger activities in Chinese fir protoplasts. Furthermore, the vector containing Cas gene driven by Cula11 promoter and sgRNA driven by the newly isolated CulaU6b polyIII promoters were introduced into Chinese fir protoplasts, and CRISPR/Cas mediated gene knock-out event was successfully achieved. More importantly, compared with the commonly used promoters in the genetic engineering in angiosperms, Cula11 promoter has much stronger activity than CaM35S promoter in transgenic poplar, and ZmUbi promoter in transgenic rice, respectively, indicating its potential application in poplar and rice genetic engineering. Overall, the novel putative constitutive gene promoters reported here will have great potential application in gymnosperm and angiosperm biotechnology, and the transient gene expression system established here will serve as a useful tool for the molecular and genetic analyses of Chinese fir genes.

Repurposing 9-Aminoacridine as an Adjuvant Enhances the Antimicrobial Effects of Rifampin against Multidrug-Resistant Klebsiella pneumoniae.

The increasing occurrence of extensively drug-resistant and pan-drug-resistant K. pneumoniae has posed a serious threat to global public health. Therefore, new antimicrobial strategies are urgently needed to combat these resistant K. pneumoniae-related infections. Drug repurposing and combination are two effective strategies to solve this problem. By a high-throughput screening assay of FDA-approved drugs, we found that the potential small molecule 9-aminoacridine (9-AA) could be used as an antimicrobial alone or synergistically with rifampin (RIF) against extensively/pan-drug-resistant K. pneumoniae. In addition, 9-AA could overcome the shortcomings of RIF by reducing the occurrence of resistance. Mechanistic studies revealed that 9-AA interacted with bacterial DNA and disrupted the proton motive force in K. pneumoniae. Through liposomeization and combination with RIF, the cytotoxicity of 9-AA was significantly reduced without affecting its antimicrobial activity. In addition, we demonstrated the in vivo antimicrobial activity of 9-AA combined with RIF without detectable toxicity. In summary, 9-AA has the potential to be an antimicrobial agent or a RIF adjuvant for the treatment of multidrug-resistant K. pneumoniae infections. IMPORTANCE Klebsiella pneumoniae is a leading cause of clinically acquired infections. The increasing occurrence of drug-resistant K. pneumoniae has posed a serious threat to global public health. We found that the potential small molecule 9-AA could be used as an antimicrobial alone or synergistically with RIF against drug-resistant K. pneumoniae in vitro and with low resistance occurrence. The combination of 9-AA or 9-AA liposomes with RIF possesses effective antimicrobial activity in vivo without detected toxicity. 9-AA exerted its antimicrobial activity by interacting with specific bacterial DNA and disrupting the proton motive force in K. pneumoniae. In summary, we found that 9-AA has the potential to be developed as a new antibacterial agent and adjuvant for RIF. Therefore, our study can reduce the risk of antimicrobial resistance and provide an option for the exploitation of new clinical drugs and a theoretical basis for the research on a new antimicrobial agent.

Antibacterial and antibiofilm efficacy of repurposing drug hexestrol against methicillin-resistant Staphylococcus aureus.

There has been an explosion in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) because of the indiscriminate use of antibiotics. In this study, we repurposed hexestrol (HXS) as an antibacterial agent to fight planktonic and biofilm-related MRSA infections. HXS is a nonsteroidal synthetic estrogen that targets estrogen receptors (ERα and ERß) and has been used as a hormonal antineoplastic agent. In our work, the minimum inhibitory concentrations (MICs) were determined using the antimicrobial susceptibility of MSSA and MRSA strains. Anti-biofilm activity was evaluated using biofilm inhibition and eradication assays. Biofilm-related genes were analyzed with or without HXS treatment using RTqPCR analysis of S. aureus. HXS was tested using the checkerboard dilution assay to identify antibiotics that may have synergistic effects. Measurement of ATP and detection of ATPase allowed the determination of bacterial energy metabolism. As shown in the results, HXS showed effective antimicrobial activity against S. aureus, including both type strains and clinical isolations, with MICs of 16 µg/mL. Sub-HXS strongly inhibited the adhesion of S. aureus. The content of extracellular polymeric substances (EPS) and the relative transcription levels of eno, sacC, clfA, pls and fnbpB were reduced after HXS treatment. HXS showed antibacterial effects against S. aureus and synergistic activity with aminoglycosides by directly interfering with cellular energy metabolism. HXS inhibits adhesion and biofilm formation and eradicates biofilms formed by MRSA by reducing the expression of related genes. Furthermore, HXS increases the susceptibility of aminoglycosides against MRSA. In conclusion, HXS is a repurposed drug that may be a promising therapeutic option for MRSA infection.

Drug synergy discovery of tavaborole and aminoglycosides against Escherichia coli using high throughput screening.

High incidences of urinary tract infection (UTI) of aminoglycosides-resistant E.coli causes a severe burden for public health. A new therapeutic strategy to ease this crisis is to repurpose non-antibacterial compounds to increase aminoglycosides sensibility against multidrug resistant E.coli pathogens. Based on high throughput screening technology, we profile the antimicrobial activity of tavaborole, a first antifungal benzoxaborole drug for onychomycosis treatment, and investigate the synergistic interaction between tavaborole and aminoglycosides, especially tobramycin and amikacin. Most importantly, by resistance accumulation assay, we found that, tavaborole not only slowed resistance occurrence of aminoglycosides, but also reduced invasiveness of E.coli in combination with tobramycin. Mechanistic studies preliminary explored that tavaborole and aminoglycosides lead to mistranslation, but would be still necessary to investigate more details for further research. In addition, tavaborole exhibited low systematic toxicity in vitro and in vivo, and enhanced aminoglycoside bactericidal activity in mice peritonitis model. Collectively, these results suggest the potential of tavaborole as a novel aminoglycosides adjuvant to tackle the clinically relevant drug resistant E. coli and encourages us to discover more benzoxaborole analogues for circumvention of recalcitrant infections.

Insights into the antimicrobial effects of ceritinib against Staphylococcus aureus in vitro and in vivo by cell membrane disruption.

According to a 2019 report from the Centers of Disease Control and Prevention (CDC), methicillin-resistant Staphylococcus aureus (MRSA) was listed as one of the "serious threats" that had become a global public challenge in hospitals and community. Biofilm-associated infections and refractory persisters of S. aureus also impede the effectiveness of conventional antibiotics that have greatly increased difficulty in clinical therapy. There is an urgent need to develop new antimicrobials with antibiofilm and anti-persister capacities, and drug repurposing is the most effective and most economical solution to the problem. The present study profiles the antimicrobial activity of ceritinib, a tyrosine kinase inhibitor, against S. aureus in vitro and in vivo. We investigated the antimicrobial efficacy of ceritinib against planktonic and persistent S. aureus by a time-killing kinetics assay. Then, antibiofilm effect of ceritinib was assessed by crystal violet staining and laser confocal microscope observation. Ceritinib showed biofilm inhibition and mature biofilm eradication, and possesses robust bactericidal activity against S. aureus persisters. We also evaluated antimicrobial efficacy in vivo using a subcutaneous abscess infection model. Ceritinib ameliorated infection in a subcutaneous abscess mouse model and only showed negligible systemic toxicity in vivo. Mechanism exploration was conducted by transmission electron microscopy, fluorescently labeled giant unilamellar vesicle assays, and a series of fluorescent dyes. In conclusion, we find ceritinib represents potential bactericidal activity against MRSA by disrupting cell membrane integrity and inducing reactive oxygen species production, suggesting ceritinib has the potential to treat MRSA-related infections.

Pixantrone Sensitizes Gram-Negative Pathogens to Rifampin.

The emergence of bacterial drug resistance poses a severe threat to global public health. In particular, antimicrobial-resistant pathogens lead to a high rate of treatment failure and significantly increase mortality. Repurposing FDA-approved compounds to sensitize superbugs to conventional antibiotics provides a promising strategy to alleviate such crises. Pixantrone (PIX) has been approved for treating aggressive B-cell non-Hodgkin's lymphoma. By high-throughput drug screening, we profiled the synergistic activity between PIX and rifampin (RFP) against Gram-negative extensively drug-resistant isolates by checkerboard assay. Mechanistic studies demonstrated that PIX impacted the flagellum assembly, induced irreversible intracellular reactive oxygen species accumulation and disrupted proton motive force. In addition, the combination of PIX with RFP possesses effective antimicrobial activity against multidrug-resistant strains in vivo without detected toxicity. Collectively, these results reveal the potential of PIX in combination with RFP as a therapy option for refractory infections caused by Gram-negative pathogens. IMPORTANCE Bacterial resistance has become increasingly serious because of the widespread use and abuse of antibiotics. In particular, the emergence of multidrug-resistant bacteria has posed a serious threat to human public health. Drug repurposing, the process of finding new uses for existing drugs, provide a promising pathway to solve antimicrobial resistance. Compared to the development of novel antibiotics, this strategy leverages well-characterized pharmacology and toxicology of known drugs and is more cost-effective.

[Adverse cardiovascular effects of antiretrovirals in female mice during gestation].

Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P＜0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P＜0.05); the level of LVP+dP/dtmax was decreased (P＜0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P＜0.05 or P＜0.01), while the level of glucose was increased (P＜0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.

Cucumber-Derived Nanovesicles Containing Cucurbitacin B for Non-Small Cell Lung Cancer Therapy.

Purpose: In recent years, a variety of nanoparticles with excellent anticancer and delivery properties have emerged for cancer therapy. However, potential toxicity, high production cost and complex preparation procedures have been obstacles to their use in biomedicine. Here, we obtained cucumber-derived nanovesicles (CDNVs) at high yield and low cost by simple juicing and ultracentrifugation. The anticancer effects of CDNVs were evaluated in vitro and in vivo. Methods: Transmission electron microscope, nanoparticle tracking analysis and laser particle size analysis were used to characterize the morphology, diameter and zeta potential of CDNVs, respectively. The anticancer effects of CDNVs in vitro were evaluated by MTT and apoptosis assays. The mechanism was further explored by measuring the protein levels of signal transducer and activator of transcription 3 pathway, reactive oxygen species, cell cycle distribution and caspase activity. In-vivo anticancer efficacy was evaluated by measuring tumor volume and weight of mice in three different treatment groups (CDNVs, cucurbitacin B and PBS). Results: CDNVs inhibited proliferation of human non-small cell lung cancer cells by suppressing signal transducer and activator of transcription 3 activation, generating reactive oxygen species, promoting cell cycle arrest, and activating the caspase pathway. These CDNVs exhibited strong anticancer effects both in vitro and in vivo, and reduced the rate of tumor growth without obvious toxicity to mouse visceral organs. Compared with an equivalent dose of cucurbitacin B, CDNVs exerted stronger anticancer effects in vitro and in vivo. Conclusion: These results demonstrate that CDNVs suppress tumor growth. This study addresses the development of cancer therapeutic drugs using plant-derived nanovesicles that are cost-efficient, simple to produce in high yields, and provide an alternative approach to drug isolation that may help advance sustainability of medicinal plants.

Identification of a small molecule 0390 as a potent antimicrobial agent to combat antibiotic-resistant Escherichia coli.

Introduction: Antibiotic resistance has posed a serious challenge to global public health. With the increasing resistance emergence of E. coli and mortality caused by drug-resistant E. coli infections, it is urgent to develop novel antibiotics. Methods: By high-throughput screening assay, we found a bioactive molecule, 0390 (6056-0390), which demonstrated antimicrobial effects against E. coli. The antimicrobial effects of 0390 alone or in combination with conventional antibiotics were assessed by scanning electron microscopy, transmission electron microscopy, drug combination assay, and growth inhibition assay. In addition, we investigated the antimicrobial efficacy in subcutaneous infection model in vivo. Results: 0390 showed significant synergistic antimicrobial effects in combination with SPR741, a polymyxin B derivative, against E. coli standard strain and extensively drug-resistant (XDR) clinical isolates, and the combination exhibited good safety property in vitro. In addition, we demonstrated that the combinational treatment of 0390 and SPR741 exhibited a considerable antibacterial activity in vivo, and no tissue damage or other toxicity was observed after the therapeutic dose treatment. Discussion: To confront the issue of the infectious diseases related to E. coli and its multidrug resistant strains, potential approaches, such as new antibacterial agents with different structures from conventional antibiotics and drug combinations, are urgently needed. In this study, we have determined the in vitro and in vivo antimicrobial potential of 0390 alone or in combination with SPR741, which might be used as a treatment option for E. coli related infections.

Repurposing Sitafloxacin, Prulifloxacin, Tosufloxacin, and Sisomicin as Antimicrobials Against Biofilm and Persister Cells of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a ubiquitous bacterium found in hospitals and the surrounding environment. The ability of P. aeruginosa to form biofilms confers high-level resistance to antibiotics, and the persister cells formed in the presence of high antibacterial drug concentrations make P. aeruginosa-related infections more refractory. Further, there rarely is an effective antimicrobial alternative when biofilm- and persister cell-targeting treatment fails. Using a high-throughput screening assay, we previously identified fluoroquinolones sitafloxacin, prulifloxacin, and tosufloxacin as well as aminoglycoside sisomicin among FDA-approved drugs with significant bactericidal activity against P. aeruginosa. In addition, in our current study, these antibiotics exhibited an effective time- and dose-dependent eradication effects against the preformed biofilms of P. aeruginosa at the concentrations of 2-4 µM. These agents also exhibited bactericidal efficacy against CCCP-induced P. aeruginosa persister cells with the viable cell count decreased from 9.14 log10 CFU/mL to 6.15 (sitafloxacin), 7.59 (prulifloxacin), 4.27 (tosufloxacin), and 6.17 (sisomicin) log10 CFU/mL, respectively, following 4 h of treatment. Furthermore, sisomicin was also effective against conventional antibiotics induced persister cells in a time-dependent manner within 24 h. In addition, we confirmed the in vivo anti-biofilm efficacy of the identified antibiotics in a subcutaneous implantation biofilm-related infection model. Tosufloxacin exhibited the greatest in vivo bactericidal activity against P. aeruginosa biofilms with a reduction of 4.54 ΔLog10 CFU/mL compared to the vehicle group, followed by prulifloxacin, sitafloxacin, and sisomicin. Taken together, our results indicate that sitafloxacin, prulifloxacin, tosufloxacin, and sisomicin have great potential as alternatives for the treatment of refractory infections caused by P. aeruginosa biofilms and persister cells.

Signal-on electrochemical DNA (E-DNA) sensor for accurate quantification of nicking-assisted rolling circle amplification (N-RCA) products with attomolar sensitivity.

Rolling circle amplification (RCA) has become an increasingly important amplification technique in nucleic acid analysis, immunoassay, and molecular diagnosis due to its high specificity and sensitivity. However, the accurate quantification of RCA products via the extensively used fluorescent signaling method has been challenged primarily by the non-specific and sequence-independent binding of the fluorescent dyes to DNA. Here, we have developed a signal-on E-DNA sensor for accurate quantification of the RCA products with high specificity and sensitivity. A restriction enzyme was introduced to cleave the long tandem repeat sequences generated in the RCA reaction into many short monomers. The short monomers were then used as secondary targets to trigger the E-DNA sensor to produce an amplified redox current and thus the resulting RCA products were detected. The method was successfully applied to the detection of miR-7a with high specificity and the detection limit was as low as 0.59 fM.

Inhibitory effects of 1,3-diaminopropane on the biofilm formation of Pseudomonas aeruginosa via interaction with quorum sensing system. / 1,3-丙二胺通过群体密度感应系统对铜绿假单胞菌生物膜形成的抑制作用.

OBJECTIVES: To study the inhibitory effects of 1,3-diaminopropane on the biofilm formation of Pseudomonas aeruginosa and the underlying mechanisms. METHODS: The experiment was divided into an experimental group and a control group. Crystal violet staining was used to examine the inhibitory effects of 1,3-diaminopropane on the biofilm formation of Pseudomonas aeruginosa, and the biofilm formation was compared between the 2 groups.Initial adherence inhibition assay and swimming plate assay were used to determine the inhibitory effects of 1,3-diaminopropane on the initial adherence and swimming motility of Pseudomonas aeruginosa,and the quantification of adhered cells and swimming diameter were compared between the 2 groups. Meanwhile, Western blotting was used to detect the Flagellin production of Pseudomonas aeruginosa; real-time RT-PCR was used to detect the quorum sensing system relative genes and flagellum regulative related genes expression in the 2 groups. Finally, molecular docking assay was used to calculate the interaction between 1,3-diaminopropane and LasI. RESULTS: Compared with the control group, the biofilm formation of Pseudomonas aeruginosa was significantly inhibited in the experimental group in a dose-dependent manner (t=6.07, P<0.01).Compared with the control group, the initial adherence of Pseudomonas aeruginosa could significantly inhibit from (0.890±0.389)×106 to (0.245±0.076)×106 CFU/mL (t=3.257, P<0.05) in the experimental group (2.0 mmol/L).Compared with the control group, the swimming motility of Pseudomonas aeruginosa flagellar mediation could also inhibit in the experimental group (2.0 mmol/L). The swimming motility diameter was from (1.840±0.144) to (0.756±0.222) cm (t=7.099, P<0.01). Compared with the control group, the Flagellin production was inhibited in the experimental group. Finally, the molecular docking assay showed that the potential target of 1,3-diaminopropane was LasI. CONCLUSIONS: 1,3-diaminopropane can significantly inhibit the biofilm formation of Pseudomonas aeruginosa, which potentially targets LasI protein.