Infection and ImmunityPub Date : 2024-06-11Epub Date: 2024-05-23DOI: 10.1128/iai.00173-24
Iris George, Manivannan Sivaperuman Kalairaj, Philippe E Zimmern, Taylor H Ware, Sargurunathan Subashchandrabose
{"title":"Competitive fitness of asymptomatic bacteriuria <i>E. coli</i> strain 83972 against uropathogens in human urine.","authors":"Iris George, Manivannan Sivaperuman Kalairaj, Philippe E Zimmern, Taylor H Ware, Sargurunathan Subashchandrabose","doi":"10.1128/iai.00173-24","DOIUrl":"10.1128/iai.00173-24","url":null,"abstract":"<p><p>Urinary tract infection (UTI) is one of the most common bacterial infections worldwide. The main causative agent of UTI is uropathogenic <i>Escherichia coli</i> (UPEC). There is an immediate need for novel prophylactic and treatment strategies against UTI because of the increasing incidence of antimicrobial resistance among uropathogens. ABU 83972, an asymptomatic bacteriuria-causing <i>E. coli</i> strain<i>,</i> prevents UTI by suppressing the colonization of UPEC. However, the nature of competition and growth repression of UPEC by ABU 83972 is unclear and is the subject of our investigation. Here, we characterized the growth kinetics of ABU 83972 and uropathogens in human urine and laboratory media. Next, we performed a series of competitive co-culture experiments where ABU 83972 and uropathogens were inoculated at a 1:1 ratio in human urine and in various media, and their relative abundance was determined. In human urine, ABU 83972 outcompeted UPEC and additional uropathogens, reaching up to 90% of the total population after 24 hours of incubation. In contrast, UPEC outcompeted ABU 83972 in LB and M9 minimal media and exhibited superior colonization than ABU 83972 in the mouse urinary bladder. Since engineered living materials (ELMs) can be used to retain an organism of interest in a particular location, we developed ABU 83972-containing ELMs that effectively outcompeted UPEC in human urine. In summary, our work establishes that ABU 83972 outcompetes UPEC in a milieu- and cell-density-dependent manner, highlighting the importance of the metabolites and nutrients found in the human urine as determinants of the competitive fitness of ABU 83972.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079740","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}
Infection and ImmunityPub Date : 2024-06-11Epub Date: 2024-05-23DOI: 10.1128/iai.00058-24
Kate R Fortney, Julie A Brothwell, Teresa A Batteiger, Rory Duplantier, Barry P Katz, Stanley M Spinola
{"title":"A <i>Haemophilus ducreyi</i> strain lacking the <i>yfeABCD</i> iron transport system is virulent in human volunteers.","authors":"Kate R Fortney, Julie A Brothwell, Teresa A Batteiger, Rory Duplantier, Barry P Katz, Stanley M Spinola","doi":"10.1128/iai.00058-24","DOIUrl":"10.1128/iai.00058-24","url":null,"abstract":"<p><p><i>Haemophilus ducreyi</i> causes the genital ulcer disease chancroid and painful cutaneous ulcers in children who live in the tropics. To acquire heme from the host, <i>H. ducreyi</i> expresses a TonB-dependent hemoglobin receptor, HgbA, which is necessary and sufficient for <i>H. ducreyi</i> to progress to the pustular stage of disease in a controlled human infection model. HgbA transports hemoglobin across the outer membrane; how heme is transported across the cytoplasmic membrane is unclear. In previous studies, transcripts encoding the YfeABCD heme transporter were upregulated in experimental lesions caused by <i>H. ducreyi</i> in human volunteers, suggesting the latter may have a role in virulence. Here we constructed a double deletion mutant, 35000HPΔ<i>yfeAB</i>Δ<i>yfeCD</i>, which exhibited growth defects relative to its parent 35000HP in media containing human hemoglobin as an iron source. Five human volunteers were inoculated at three sites on the skin overlying the deltoid with each strain. The results of the trial showed that papules formed at 100% (95% CI, 71.5, 100) at both 35000HP and 35000HPΔ<i>yfeAB</i>Δ<i>yfeCD</i>-inoculated sites (<i>P</i> = 1.0). Pustules formed at 60% (95% CI, 25.9, 94.1) at parent-inoculated sites and 53% (95% CI, 18.3, 88.4) at mutant-inoculated sites (<i>P</i> = 0.79). Thus, the ABC transporter encoded by <i>yfeAB</i> and <i>yfeCD</i> was dispensable for <i>H. ducreyi</i> virulence in humans. In the absence of YfeABCD, <i>H. ducreyi</i> likely utilizes other periplasmic binding proteins and ABC-transporters such as HbpA, SapABCDF, and DppBCDF to shuttle heme from the periplasm into the cytoplasm, underscoring the importance of redundancy of such systems in gram-negative pathogens.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079729","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}
Infection and ImmunityPub Date : 2024-06-11Epub Date: 2024-05-21DOI: 10.1128/iai.00016-24
Gitanjali Bhushan, Victor Castano, Tania Wong Fok Lung, Courtney Chandler, Thomas H McConville, Robert K Ernst, Alice S Prince, Danielle Ahn
{"title":"Lipid A modification of colistin-resistant <i>Klebsiella pneumoniae</i> does not alter innate immune response in a mouse model of pneumonia.","authors":"Gitanjali Bhushan, Victor Castano, Tania Wong Fok Lung, Courtney Chandler, Thomas H McConville, Robert K Ernst, Alice S Prince, Danielle Ahn","doi":"10.1128/iai.00016-24","DOIUrl":"10.1128/iai.00016-24","url":null,"abstract":"<p><p>Polymyxin resistance in carbapenem-resistant <i>Klebsiella pneumoniae</i> bacteria is associated with high morbidity and mortality in vulnerable populations throughout the world. Ineffective antimicrobial activity by these last resort therapeutics can occur by transfer of <i>mcr-1</i>, a plasmid-mediated resistance gene, causing modification of the lipid A portion of lipopolysaccharide (LPS) and disruption of the interactions between polymyxins and lipid A. Whether this modification alters the innate host immune response or carries a high fitness cost in the bacteria is not well established. To investigate this, we studied infection with <i>K. pneumoniae</i> (KP) ATCC 13883 harboring either the <i>mcr-1</i> plasmid (p<i>mcr-1</i>) or the vector control (pBCSK) ATCC 13883. Bacterial fitness characteristics of <i>mcr-1</i> acquisition were evaluated. Differentiated human monocytes (THP-1s) were stimulated with KP bacterial strains or purified LPS from both parent isolates and isolates harboring <i>mcr-1</i>. Cell culture supernatants were analyzed for cytokine production. A bacterial pneumonia model in WT C57/BL6J mice was used to monitor immune cell recruitment, cytokine induction, and bacterial clearance in the bronchoalveolar lavage fluid (BALF). Isolates harboring <i>mcr-1</i> had increased colistin MIC compared to the parent isolates but did not alter bacterial fitness. Few differences in cytokines were observed with purified LPS from <i>mcr-1</i> expressing bacteria <i>in vitro</i>. However, in a mouse pneumonia model, no bacterial clearance defect was observed between p<i>mcr-1</i>-harboring KP and parent isolates. Consistently, no differences in cytokine production or immune cell recruitment in the BALF were observed, suggesting that other mechanisms outweigh the effect of these lipid A mutations in LPS.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070936","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":"Effect of hepatocyte damage in hepatic fibrogenesis of patients infected with <i>Schistosoma japonicum</i>.","authors":"Yaqi Lu, Wangxian Tang, Heng Zhang, Jing Liu, Shan Zhong","doi":"10.1128/iai.00026-24","DOIUrl":"10.1128/iai.00026-24","url":null,"abstract":"<p><p>Schistosomiasis is a serious public health problem, and previous studies found that liver function and hepatic cells are damaged. To evaluate the serum parameters of liver function and fibrosis in schistosomiasis patients infected with <i>Schistosoma japonicum</i> (<i>Schistosoma J</i>.) and analyze the correlations between liver function and serum fibrosis markers in patients infected with <i>Schistosoma J</i>., this retrospective study enrolled 133 patients. The study population was divided into four groups: healthy people control group (<i>n</i> = 20), chronic schistosomiasis without liver cirrhosis (CS) group (<i>n</i> = 21), schistosomiasis cirrhosis without hypoalbuminemia (SC-HA) group (<i>n</i> = 68), and schistosomiasis cirrhosis with hypoalbuminemia (SC +HA) group (<i>n</i> = 24). Clinical and laboratory data were collected for analysis. In the multiple comparison of abnormal rates of aspartate aminotransferase (AST) and total bilirubin (TBIL), the abnormal rate of the SC +HA group was significantly higher than that of the other three groups (<i>P</i> < 0.05), and the abnormal rate of γ-GT in the SC +HA group was significantly higher than that in the control group (<i>P</i> < 0.05). Multiple comparison results of serum levels of fibrosis markers showed that the SC group had a significantly higher level of indexes than other groups (<i>P</i> < 0.05). The levels of TGF-β1 in the CS group, SC-HA group and SC +HA group were significantly higher than those in the control group (<i>P</i> < 0.001). Our study demonstrated that the liver function and hepatic cells were damaged with the progression of liver disease in patients infected with <i>Schistosoma J.</i>, and they played an important role in the occurrence and development of liver fibrosis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065335","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}
Infection and ImmunityPub Date : 2024-06-11Epub Date: 2024-05-22DOI: 10.1128/iai.00020-24
Hailey Barker, Mariola J Ferraro
{"title":"Exploring the versatile roles of the endocannabinoid system and phytocannabinoids in modulating bacterial infections.","authors":"Hailey Barker, Mariola J Ferraro","doi":"10.1128/iai.00020-24","DOIUrl":"10.1128/iai.00020-24","url":null,"abstract":"<p><p>The endocannabinoid system (ECS), initially identified for its role in maintaining homeostasis, particularly in regulating brain function, has evolved into a complex orchestrator influencing various physiological processes beyond its original association with the nervous system. Notably, an expanding body of evidence emphasizes the ECS's crucial involvement in regulating immune responses. While the specific role of the ECS in bacterial infections remains under ongoing investigation, compelling indications suggest its active participation in host-pathogen interactions. Incorporating the ECS into the framework of bacterial pathogen infections introduces a layer of complexity to our understanding of its functions. While some studies propose the potential of cannabinoids to modulate bacterial function and immune responses, the outcomes inherently hinge on the specific infection and cannabinoid under consideration. Moreover, the bidirectional relationship between the ECS and the gut microbiota underscores the intricate interplay among diverse physiological processes. The ECS extends its influence far beyond its initial discovery, emerging as a promising therapeutic target across a spectrum of medical conditions, encompassing bacterial infections, dysbiosis, and sepsis. This review comprehensively explores the complex roles of the ECS in the modulation of bacteria, the host's response to bacterial infections, and the dynamics of the microbiome. Special emphasis is placed on the roles of cannabinoid receptor types 1 and 2, whose signaling intricately influences immune cell function in microbe-host interactions.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075952","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}
Infection and ImmunityPub Date : 2024-06-11Epub Date: 2024-05-09DOI: 10.1128/iai.00065-24
Sozaburo Ihara, Brian V Nguyen, Yukiko Miyamoto, Lars Eckmann
{"title":"Mucosal vaccination in a murine gnotobiotic model of <i>Giardia lamblia</i> infection.","authors":"Sozaburo Ihara, Brian V Nguyen, Yukiko Miyamoto, Lars Eckmann","doi":"10.1128/iai.00065-24","DOIUrl":"10.1128/iai.00065-24","url":null,"abstract":"<p><p><i>Giardia lamblia</i> is an important protozoan cause of diarrheal disease worldwide, delayed development and cognitive impairment in children in low- and middle-income countries, and protracted post-infectious syndromes in developed regions. <i>G. lamblia</i> resides in the lumen and at the epithelial surface of the proximal small intestine but is not mucosa invasive. The protozoan parasite is genetically diverse with significant genome differences across strains and assemblages. Animal models, particularly murine models, have been instrumental in defining mechanisms of host defense against <i>G. lamblia</i>, but mice cannot be readily infected with most human pathogenic strains. Antibiotic pretreatment can increase susceptibility, suggesting that the normal microbiota plays a role in controlling <i>G. lamblia</i> infection in mice, but the broader implications on susceptibility to diverse strains are not known. Here, we have used gnotobiotic mice to demonstrate that robust intestinal infection can be achieved for a broad set of human-pathogenic strains of the genetic assemblages A and B. Furthermore, gnotobiotic mice were able to eradicate infection with a similar kinetics to conventional mice after trophozoite challenge. Germ-free mice could also be effectively immunized by the mucosal route with a protective antigen, α1-giardin, in a manner dependent on CD4 T cells. These results indicate that the gnotobiotic mouse model is powerful for investigating acquired host defenses in giardiasis, as the mice are broadly susceptible to diverse <i>G. lamblia</i> strains yet display no apparent defects in mucosal immunity needed for controlling and eradicating this lumen-dwelling pathogen.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897407","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}
Infection and ImmunityPub Date : 2024-06-11Epub Date: 2024-05-10DOI: 10.1128/iai.00540-23
Susan M Noh, Jessica Ujczo, Debra C Alperin, Shelby M Jarvis, Muna S M Solyman, Roberta Koku, Olalekan C Akinsulie, Elizabeth E Hoffmann
{"title":"Identification of <i>Anaplasma marginale</i> adhesins for entry into <i>Dermacentor andersoni</i> tick cells using phage display.","authors":"Susan M Noh, Jessica Ujczo, Debra C Alperin, Shelby M Jarvis, Muna S M Solyman, Roberta Koku, Olalekan C Akinsulie, Elizabeth E Hoffmann","doi":"10.1128/iai.00540-23","DOIUrl":"10.1128/iai.00540-23","url":null,"abstract":"<p><p><i>Anaplasma marginale</i> is an obligate, intracellular, tick-borne bacterial pathogen that causes bovine anaplasmosis, an often severe, production-limiting disease of cattle found worldwide. Methods to control this disease are lacking, in large part due to major knowledge gaps in our understanding of the molecular underpinnings of basic host-pathogen interactions. For example, the surface proteins that serve as adhesins and, thus, likely play a role in pathogen entry into tick cells are largely unknown. To address this knowledge gap, we developed a phage display library and screened 66 <i>A</i>. <i>marginale</i> proteins for their ability to adhere to <i>Dermacentor andersoni</i> tick cells. From this screen, 17 candidate adhesins were identified, including OmpA and multiple members of the Msp1 family, including Msp1b, Mlp3, and Mlp4. We then measured the transcript of <i>ompA</i> and all members of the <i>msp1</i> gene family through time, and determined that <i>msp1b</i>, <i>mlp2</i>, and <i>mlp4</i> have increased transcript during tick cell infection, suggesting a possible role in host cell binding or entry. Finally, Msp1a, Msp1b, Mlp3, and OmpA were expressed as recombinant protein. When added to cultured tick cells prior to <i>A. marginale</i> infection, all proteins except the C-terminus of Msp1a reduced <i>A. marginale</i> entry by 2.2- to 4.7-fold. Except OmpA, these adhesins lack orthologs in related pathogens of humans and animals, including <i>Anaplasma phagocytophilum</i> and the <i>Ehrlichia</i> spp., thus limiting their utility in a universal tick transmission-blocking vaccine. However, this work greatly advances efforts toward developing methods to control bovine anaplasmosis and, thus, may help improve global food security.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897406","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}
Chelsea A. OsbronCrystal LawsonNolan HannaHeather S. KoehlerAlan G. Goodman1School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA2Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USASunny Shin
{"title":"Caspase-8 activity mediates TNFα production and restricts Coxiella burnetii replication during murine macrophage infection","authors":"Chelsea A. OsbronCrystal LawsonNolan HannaHeather S. KoehlerAlan G. Goodman1School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA2Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USASunny Shin","doi":"10.1128/iai.00053-24","DOIUrl":"https://doi.org/10.1128/iai.00053-24","url":null,"abstract":"Infection and Immunity, Ahead of Print. <br/>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259310","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}
Lee Fuller1Fuller Laboratories, Fullerton, California, USADe’Broski R. Herbert
{"title":"Continuous in vitro propagation of Babesia microti","authors":"Lee Fuller1Fuller Laboratories, Fullerton, California, USADe’Broski R. Herbert","doi":"10.1128/iai.00481-23","DOIUrl":"https://doi.org/10.1128/iai.00481-23","url":null,"abstract":"Infection and Immunity, Ahead of Print. <br/>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259859","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":"Article of Significant Interest in This Issue.","authors":"","doi":"10.1128/iai.00182-24","DOIUrl":"10.1128/iai.00182-24","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859504","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}