Infection and Immunity最新文献

{"title":"Plant phenolics inhibit focal adhesion kinase and suppress host cell invasion by uropathogenic <i>Escherichia coli</i>.","authors":"Adam J Lewis, Amanda C Richards, Alejandra A Mendez, Bijaya K Dhakal, Tiffani A Jones, Jamie L Sundsbak, Danelle S Eto, Alexis A Rousek, Matthew A Mulvey","doi":"10.1128/iai.00080-24","DOIUrl":"10.1128/iai.00080-24","url":null,"abstract":"<p><p>Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here, we tested a panel of four well-studied phenolic compounds-caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate-for the effects on host cell adherence and invasion by uropathogenic <i>Escherichia coli</i> (UPEC). These bacteria, which are the leading cause of UTIs, can bind and subsequently invade bladder epithelial cells via an actin-dependent process. Intracellular UPEC reservoirs within the bladder are often protected from antibiotics and host defenses and likely contribute to the development of chronic and recurrent infections. In cell culture-based assays, only resveratrol had a notable negative effect on UPEC adherence to bladder cells. However, both CAPE and resveratrol significantly inhibited UPEC entry into the host cells, coordinate with attenuated phosphorylation of the host actin regulator Focal Adhesion Kinase (FAK or PTK2) and marked increases in the numbers of focal adhesion structures. We further show that the intravesical delivery of resveratrol inhibits UPEC infiltration of the bladder mucosa in a murine UTI model and that resveratrol and CAPE can disrupt the ability of other invasive pathogens to enter host cells. Together, these results highlight the therapeutic potential of molecules like CAPE and resveratrol, which could be used to augment antibiotic treatments by restricting pathogen access to protective intracellular niches.IMPORTANCEUrinary tract infections (UTIs) are exceptionally common and increasingly difficult to treat due to the ongoing rise and spread of antibiotic-resistant pathogens. Furthermore, the primary cause of UTIs, uropathogenic <i>Escherichia coli</i> (UPEC), can avoid antibiotic exposure and many host defenses by invading the epithelial cells that line the bladder surface. Here, we identified two plant-derived phenolic compounds that disrupt activation of the host machinery needed for UPEC entry into bladder cells. One of these compounds, resveratrol, effectively inhibited UPEC invasion of the bladder mucosa in a mouse UTI model, and both phenolic compounds significantly reduced host cell entry by other invasive pathogens. These findings suggest that select phenolic compounds could be used to supplement existing antibacterial therapeutics by denying uropathogens shelter within host cells and tissues and help explain some of the benefits attributed to traditional plant-based medicines.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0008024"},"PeriodicalIF":2.9,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptidoglycan fragment release and NOD activation by commensal <i>Neisseria</i> species from humans and other animals.","authors":"Tiffany N Harris-Jones, Jia Mun Chan, Kathleen T Hackett, Nathan J Weyand, Ryan E Schaub, Joseph P Dillard","doi":"10.1128/iai.00004-24","DOIUrl":"10.1128/iai.00004-24","url":null,"abstract":"<p><p><i>Neisseria gonorrhoeae</i>, a human restricted pathogen, releases inflammatory peptidoglycan (PG) fragments that contribute to the pathophysiology of pelvic inflammatory disease. The genus <i>Neisseria</i> is also home to multiple species of human- or animal-associated <i>Neisseria</i> that form part of the normal microbiota. Here we characterized PG release from the human-associated nonpathogenic species <i>Neisseria lactamica</i> and <i>Neisseria mucosa</i> and animal-associated <i>Neisseria</i> from macaques and wild mice. An <i>N. mucosa</i> strain and an <i>N. lactamica</i> strain were found to release limited amounts of the proinflammatory monomeric PG fragments. However, a single amino acid difference in the PG fragment permease AmpG resulted in increased PG fragment release in a second <i>N. lactamica</i> strain examined. <i>Neisseria</i> isolated from macaques also showed substantial release of PG monomers. The mouse colonizer <i>Neisseria musculi</i> exhibited PG fragment release similar to that seen in <i>N. gonorrhoeae</i> with PG monomers being the predominant fragments released. All the human-associated species were able to stimulate NOD1 and NOD2 responses. <i>N. musculi</i> was a poor inducer of mouse NOD1, but <i>ldcA</i> mutation increased this response. The ability to genetically manipulate <i>N. musculi</i> and examine effects of different PG fragments or differing amounts of PG fragments during mouse colonization will lead to a better understanding of the roles of PG in <i>Neisseria</i> infections. Overall, we found that only some nonpathogenic <i>Neisseria</i> have diminished release of proinflammatory PG fragments, and there are differences even within a species as to types and amounts of PG fragments released.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0000424"},"PeriodicalIF":2.9,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the hypothetical protein BB0616 in the murine infection of Borrelia burgdorferi","authors":"Christina Thompson, Connor Waldron, Sierra George, Zhiming Ouyang","doi":"10.1128/iai.00090-24","DOIUrl":"https://doi.org/10.1128/iai.00090-24","url":null,"abstract":"Lyme disease is the most common vector-borne infection, with an estimated 476,000\u0000new cases annually in the United States (1, 2). Clinical manifestations range from characteristic skin lesions called “erythema\u0000migrans” to carditis, arthritis, and neuroborreliosis. This disease is caused by the\u0000spirochetal pathogen Borrelia burgdorferi (also known as Borreliella burgdorferi), which is transmitted to humans through hematophagous bites of an arthropod tick\u0000vector (usually Ixodes ticks) (3–5). B. burgdorferi is maintained in nature through an infectious cycle involving ticks and mammalian\u0000hosts. The acquisition of B. burgdorferi occurs when newly hatched larvae feed on infected reservoir hosts, e.g., small rodents,\u0000during which B. burgdorferi enters the ticks together with the bloodmeal and then colonizes the tick midgut.\u0000Following colonization, spirochetes reside in this nutritionally limited environment\u0000through the molt into the nymphal stage. When nymphs attach to and take a bloodmeal\u0000on the subsequent hosts, spirochetes traverse the tick midgut peritrophic membrane,\u0000migrate through the hemocoel to the salivary gland, and then are deposited into the\u0000host skin to initiate infection. Once in the host, B. burgdorferi disseminates hematogenously into distant organs and causes tissue damage.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"3 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate phase production of IFN-γ by memory and effector T cells expressing early activation marker CD69 during infection with Cryptococcus deneoformans in the lungs","authors":"Anna Miyahara, Aya Umeki, Ko Sato, Toshiki Nomura, Hideki Yamamoto, Tomomitsu Miyasaka, Daiki Tanno, Ikumi Matsumoto, Tong Zong, Takafumi Kagesawa, Akiho Oniyama, Kotone Kawamura, Xiaoliang Yuan, Rin Yokoyama, Yuki Kitai, Emi Kanno, Hiromasa Tanno, Hiromitsu Hara, Sho Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Keiko Ishii, Kazuyoshi Kawakami","doi":"10.1128/iai.00024-24","DOIUrl":"https://doi.org/10.1128/iai.00024-24","url":null,"abstract":"The two sister species, Cryptococcus neoformans (formerly C. neoformans var. grubii, serotype A) and C. deneoformans (formerly C. neoformans var. neoformans, serotype D), are yeast-type fungal pathogens characterized by thick capsules composed\u0000of polysaccharides such as glucuronoxylomannan and galactoxylomannan (1). These fungi grow in pigeon droppings and enter the lungs via an airborne route.\u0000While most healthy individuals experience asymptomatic infection, marked by granulomatous\u0000lesions in the lungs caused by these fungi, immunocompromised hosts with severely\u0000impaired cellular immunity, such as those with AIDS, frequently suffer from severe\u0000lung lesions and disseminated infections that extend to the central nervous system\u0000(2).","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"46 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CpxRA two-component system of adherent and invasive Escherichia coli contributes to epithelial cell invasion and early-stage intestinal fitness in a dysbiotic mouse model mediated by type 1 fimbriae expression","authors":"Tsuyoshi Miki, Masahiro Ito, Nobuhiko Okada, Takeshi Haneda","doi":"10.1128/iai.00132-24","DOIUrl":"https://doi.org/10.1128/iai.00132-24","url":null,"abstract":"Crohn’s disease (CD) is an inflammatory bowel disease that is represented as a chronic\u0000inflammatory disorder of the gastrointestinal tract (1, 2). Although the detailed etiology of CD is still unclear, several factors appear to\u0000be involved in the onset and progression of CD, including genetic, immunological,\u0000and infectious factors (3–5). Notably, gut dysbiosis accompanied by gastrointestinal inflammation is the most\u0000common manifestation (6, 7). Given that gut dysbiosis is defined by decreased bacterial diversity and an imbalanced\u0000microbiota composition, it is speculated that certain bacteria, known as pathobionts,\u0000typically existing in symbiosis but capable of triggering disease under specific conditions,\u0000are involved in CD. To date, some bacterial species have been identified as suspicious\u0000(6–14). Among such bacteria, a pathobiont, adherent and invasive Escherichia coli (AIEC), is significantly prevalent in CD patients and has been widely accepted to\u0000be linked to CD (12, 15–18). AIEC strongly adheres to and invades intestinal epithelial cells, penetrates the\u0000epithelial barrier, survives within macrophages, moves to deep tissues, and induces\u0000inflammatory responses, along with secreting proinflammatory cytokines (19).","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"107 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prostaglandin D2 antagonist asapiprant ameliorates clinical severity in young hosts infected with invasive Streptococcus pneumoniae","authors":"Manmeet BhallaSydney HerringAlexsandra LenhardJoshua R. WheelerFred AswadKlaus KlumppJustin ReboYan WangKevin WilhelmsenKristen FortneyElsa N. Bou Ghanem1Department of Microbiology and Immunology, School of Medicine, University at Buffalo, Buffalo, New York, USA2Department of Pathology, Stanford University, Stanford, California, USA3BIOAGE Labs Inc., Richmond, California, USA, Nancy E. Freitag","doi":"10.1128/iai.00522-23","DOIUrl":"https://doi.org/10.1128/iai.00522-23","url":null,"abstract":"Infection and Immunity, Ahead of Print. <br/>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"25 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140616847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCR2-dependent CX3CR1+ colonic macrophages promote Enterococcus faecalis dissemination","authors":"Kevin C. Jennings, Kaitlin E. Johnson, Michael A. Hayward, Christopher J. Kristich, Nita H. Salzman","doi":"10.1128/iai.00006-24","DOIUrl":"https://doi.org/10.1128/iai.00006-24","url":null,"abstract":"Enterococci are Gram-positive commensal bacteria found in the gastrointestinal tract\u0000of most mammals. Although enterococci are typically non-pathogenic, they are intrinsically\u0000resistant to cephalosporin antibiotics, and treatment with cephalosporins can lead\u0000to opportunistic infections in humans and mice (1, 2). Currently, enterococci are the third leading cause of infectious endocarditis,\u0000with Enterococcus faecalis contributing to &gt;90% of reported enterococcus-related cases (3, 4). Furthermore, the rising prevalence of vancomycin-resistant enterococci, predominantly\u0000Enterococcus faecium, has made enterococci a leading cause of hospital-acquired infections in the United\u0000States (5). Nevertheless, most individuals colonized with enterococci, including E. faecalis or E. faecium, do not succumb to infections (6, 7). This highlights the generally commensal nature of enterococci but suggests a gap\u0000in our understanding of the preconditions for opportunistic infections by these pathobionts.\u0000To date, the mechanisms by which commensal enterococci subvert host immunity to become\u0000pathogenic remain poorly understood.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"219 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140616844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial surface lipoproteins mediate epithelial microinvasion by Streptococcus pneumoniae","authors":"Jia Mun ChanElisa Ramos-SevillanoModupeh BettsHolly U. WilsonCaroline M. WeightAmbrine Houhou-OusalahGabriele PollaraJeremy S. BrownRobert S. Heyderman1Research Department of Infection, Division of Infection and Immunity, University College London, London, United Kingdom2UCL Respiratory, Division of Medicine, University College London, London, United Kingdom, Nancy E. Freitag","doi":"10.1128/iai.00447-23","DOIUrl":"https://doi.org/10.1128/iai.00447-23","url":null,"abstract":"Infection and Immunity, Ahead of Print. <br/>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"11 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasmodium yoelii surface-related antigen (PySRA) modulates the host pro-inflammatory responses via binding to CD68 on macrophage membrane","authors":"Xin Feng, Jia-Li Yu, Yi-Fan Sun, Chen-Yan Du, Yao Shen, Lu Zhang, Wei-Zhong Kong, Su Han, Yang Cheng","doi":"10.1128/iai.00113-24","DOIUrl":"https://doi.org/10.1128/iai.00113-24","url":null,"abstract":"Malaria is an important mosquito-borne disease that seriously endangers human life\u0000and health. In 2021, global reports indicate that nearly 247 million malaria cases\u0000caused 619,000 deaths (1). Malaria is a highly complex disease with a variety of pathologic manifestations.\u0000In the early stages of infection, most patients showed general symptoms such as fever,\u0000sweat, and headache. Meanwhile, the symptoms of cerebral malaria, severe anemia, and\u0000respiratory distress occurred with the increase in parasites during the erythrocytic\u0000stage, leading to severe malaria (2–4).","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"2 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flagellin-modulated inflammasome pathways characterize the human alveolar macrophage response to Burkholderia pseudomallei, a lung-tropic pathogen","authors":"Lara Lovelace-MaconSarah M. BakerDeirdre DuckenSudeshna SealGuilhem RerolleDiane TomitaKelly D. SmithSandra SchwarzT. Eoin West1Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA2Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA3Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA4Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Tuebingen, Germany5Department of Global Health, University of Washington, Seattle, Washington, USA, Victor J. Torres","doi":"10.1128/iai.00060-24","DOIUrl":"https://doi.org/10.1128/iai.00060-24","url":null,"abstract":"Infection and Immunity, Ahead of Print. <br/>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"34 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}