{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:31:34Z","timestamp":1777923094465,"version":"3.51.4"},"reference-count":35,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                    is an opportunistic pathogen, which usually presents multiple antibiotic resistance. Host-directed therapy involves modulating the host defense system and the interplay between innate and adaptive immunity is a new strategy for designing anti-infection drugs. Memantine (MEM), a drug used to treat Alzheimer's disease, has a good inhibitory effect on neonatal mice with\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    -associated bacteremia and meningitis; however, the inhibitory effect and mechanisms of MEM against\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    infection remain unclear. Here, we investigated whether MEM could inhibit\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    infection and explored the potential mechanisms. MEM significantly promoted the bactericidal effect of neutrophils against\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    and its drug-resistant strain. The combination index of MEM and amikacin (AMK) was &lt;1.\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    experiments showed that the bacteremia and inflammation severities in the MEM-treated group were less than those in the untreated group, and the bacterial load in the organs was significantly less than that in the control group. Combining MEM with the reactive oxygen species (ROS) inhibitor,\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -acetyl-\n                    <jats:sc>l<\/jats:sc>\n                    -cysteine, weakened the anti-infective effect of MEM. MEM increased the expression of NADPH p67phox and promoted neutrophilic ROS production. Deleting the p67phox gene significantly weakened the effects of MEM on ROS generation and improving bactericidal effect of neutrophils. In conclusion, MEM promoted the bactericidal effect of neutrophils against\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    and its drug-resistant strain, and had a synergistic antibacterial effect when combined with AMK. MEM may exert its anti-infective effects by promoting neutrophilic bactericidal activity via increasing the expression level of p67phox and further stimulating ROS generation.\n                  <\/jats:p>","DOI":"10.1089\/mdr.2020.0511","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T15:26:06Z","timestamp":1628263566000},"page":"7-17","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Memantine Promotes Bactericidal Effect of Neutrophils Against Infection with\n                    <i>Pseudomonas aeruginosa<\/i>\n                    and Its Drug-Resistant Strain, by Improving Reactive Oxygen Species Generation"],"prefix":"10.1177","volume":"28","author":[{"given":"Yi","family":"Xiao","sequence":"first","affiliation":[{"name":"Guangzhou Key Laboratory of Enhanced Recovery After Abdominal Surgery, Department of Clinical Laboratory, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tie-Song","family":"Zhang","sequence":"additional","affiliation":[{"name":"Kunming Key Laboratory of Children Infection and Immunity, Yunnan Institute of Pediatrics, Kunming Children's Hospital, Kunming, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Ward III, Hunan Cancer Hospital, Changsha, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Enhanced Recovery After Abdominal Surgery, Department of Clinical Laboratory, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3304-278X","authenticated-orcid":false,"given":"Shao-Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Diseases, Southern Medical University, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Ting","family":"Zeng","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Enhanced Recovery After Abdominal Surgery, Department of Clinical Laboratory, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng-He","family":"Huang","sequence":"additional","affiliation":[{"name":"Kunming Key Laboratory of Children Infection and Immunity, Yunnan Institute of Pediatrics, Kunming Children's Hospital, Kunming, China."},{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Diseases, Southern Medical University, Guangzhou, China."},{"name":"Department of Pediatrics, Saban Research Institute, University of Southern California, Children's Hospital Los Angeles, Los Angeles, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Yan","family":"Deng","sequence":"additional","affiliation":[{"name":"KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Peng","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Enhanced Recovery After Abdominal Surgery, Department of Clinical Laboratory, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China."},{"name":"KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2014.10.018"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.7754\/Clin.Lab.2013.130325"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.09.108"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2020.03.017"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2020.03.009"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom5031762"},{"key":"e_1_3_5_8_2","first-page":"e1514","volume":"5","author":"Czyz D.M.","year":"2014","unstructured":"Czyz D.M., , Potluri L.P, , Jain-Gupta N., et al. 2014. Host-directed antimicrobial drugs with broad-spectrum efficacy against intracellular bacterial pathogens. mBio, 5:e1514\u2013e1534.","journal-title":"Host-directed antimicrobial drugs with broad-spectrum efficacy against intracellular bacterial pathogens. mBio"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700474"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12252"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2458"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02781-14"},{"key":"e_1_3_5_13_2","first-page":"e02021","volume":"10","author":"Rowe-Magnus D.A.","year":"2019","unstructured":"Rowe-Magnus D.A., , Kao A.Y, , Prieto A.C, , Pu M., , and Kao C.. 2019. Cathelicidin peptides restrict bacterial growth via membrane perturbation and induction of reactive oxygen species. mBio, 10:e02021-19.","journal-title":"Cathelicidin peptides restrict bacterial growth via membrane perturbation and induction of reactive oxygen species. mBio"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1586\/ern.11.132"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.077172"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2015.08.002"},{"key":"e_1_3_5_17_2","first-page":"e121911","article-title":"Repositioning of memantine as a potential novel therapeutic agent against meningitic E","volume":"10","author":"Yu J.Y.","year":"2015","unstructured":"Yu J.Y., , Zhang B., , Peng L., et al. 2015. Repositioning of memantine as a potential novel therapeutic agent against meningitic E. coli-induced pathogenicities through disease-associated alpha7 cholinergic pathway and RNA sequencing-based transcriptome analysis of host inflammatory responses. PLoS One, 10:e121911.","journal-title":"coli-induced pathogenicities through disease-associated alpha7 cholinergic pathway and RNA sequencing-based transcriptome analysis of host inflammatory responses. PLoS One"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004593"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12015"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu091"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.01.008"},{"key":"e_1_3_5_22_2","first-page":"e01932","volume":"9","author":"Chiang C.Y.","year":"2018","unstructured":"Chiang C.Y., , Uzoma I., , Moore R.T, et al. 2018. Mitigating the impact of antibacterial drug resistance through host-directed therapies: current Progress, outlook, and challenges. mBio, 9:e01932-17.","journal-title":"Mitigating the impact of antibacterial drug resistance through host-directed therapies: current Progress, outlook, and challenges. mBio"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41260-8"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003946"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004818"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2018.1524870"},{"key":"e_1_3_5_27_2","first-page":"161","article-title":"Efficacy of memantine hydrochloride in neuropathic pain","volume":"25","author":"Nair A.S.","year":"2019","unstructured":"Nair A.S., , and Sahoo R.K.. 2019. Efficacy of memantine hydrochloride in neuropathic pain. Indian J. Palliat. Care, 25:161\u2013162.","journal-title":"Indian J. Palliat. Care"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.4103\/aian.AIAN_294_18"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25396"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00047"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_3_5_32_2","volume-title":"et al","author":"Daigo K.","unstructured":"Daigo K., , Yamaguchi N., , Kawamura T., et al. 2012. The proteomic profile of circulating pentraxin 3 (PTX3) complex in sepsis demonstrates the interaction with azurocidin 1 and other components of neutrophil extracellular traps. Mol. 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