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Infection and Immunity

In Hwang Kim, So-Yeon Kim, Na-Young Park, Yancheng Wen, Keun-Woo Lee, So-Young Yoon, Haneul Jie, Kyu-Ho Lee, Kun-Soo Kim
Vibrio vulnificus , an opportunistic human pathogen, produces cyclo (L-Phe-L-Pro) (cFP), which serves as a signaling molecule controlling the ToxR-dependent expression of innate bacterial genes, and also as a virulence factor eliciting pathogenic effects on human cells by enhancing intracellular reactive oxygen species levels. We found that cFP facilitated the protection of V. vulnificus against hydrogen peroxide. At a concentration of 1 mM, cFP enhanced the level of the transcriptional regulator RpoS which, in turn, induced expression of katG , encoding hydroperoxidase I, an enzyme that detoxifies H2 O2 to overcome the oxidative stress...
June 18, 2018: Infection and Immunity
Olivier Huck, Jian You, Xianxian Han, Bin Cai, James Panek, Salomon Amar
Rheumatoid arthritis (RA) is an inflammatory disease that has been linked to several risk factors including periodontitis. Identification of new anti-inflammatory compounds to treat arthritis is needed. We had previously demonstrated the beneficial effect of Kava-241, a kavain derived compound, in the management of Porphyromonas gingivalis induced periodontitis. The present study evaluated systemic and articular effects of Kava-241 in an infective arthritis murine model triggered by P.gingivalis bacterial inoculation and primed with collagen antibody cocktail (CIA) to induce joint inflammation and tissular destruction...
June 18, 2018: Infection and Immunity
Md Mahmudul Hasan, Jose E Teixeira, Christopher D Huston
Entamoeba histolytica is a protozoan parasite that causes invasive amoebiasis when it invades the human colon. Tissue invasion requires a shift from an adhesive lifestyle in the colonic lumen to a motile and extracellular matrix (ECM) degradative lifestyle in the colonic tissue layers. How the parasite regulates between these two lifestyles is largely unknown. Previously, we showed that silencing the E. histolytica surface metalloprotease EhMSP-1 results in parasites that are hyperadherent and less motile. Trying to better understand the molecular mechanism of this phenotype, we now show that the EhMSP-1 silenced parasites cannot efficiently form specialized dot-like polymerized actin (F-actin) structures upon interaction with the human ECM component fibronectin...
June 18, 2018: Infection and Immunity
Sharmeen Nishat, Leah M Wuescher, Randall G Worth
Staphylococcus aureus is a major human pathogen that can cause mild to severe life threatening infections in many tissues and organs. Platelets are known to participate in protection against S. aureus by directly killing and enhancing the activities of neutrophils and macrophages in clearing S. aureus infection. Platelets have also been shown to induce monocyte differentiation into dendritic cells and to enhance activation of dendritic cells. Therefore, in the present study, we explored the role of platelets in enhancing bone marrow derived dendritic cell (BMDC) function against S...
June 18, 2018: Infection and Immunity
Glen M Scholz, Jacqueline E Heath, Jiamin Aw, Eric C Reynolds
IL-36 cytokines are important regulators of mucosal homeostasis and inflammation. We have previously established that oral epithelial cells upregulate IL-36γ expression in response to the bacterial pathogen Porphyromonas gingivalis Here, we have established that IL-36γ can stimulate the gene expression of mechanistically-distinct antimicrobial proteins, including the peptidoglycan amidase PGLYRP2, in oral epithelial cells (e.g. TIGK cells). PGLYRP2 gene expression was not stimulated by either IL-17 or IL-22, and thus demonstrating selectivity in the regulation of PGLYRP2 by IL-36γ...
June 18, 2018: Infection and Immunity
Samantha G Palace, Megan K Proulx, Rose L Szabady, Jon D Goguen
Virulence of Yersinia pestis in mammals requires the type III secretion system, which delivers seven effector proteins into the cytoplasm of host cells to undermine immune responses. All seven of these effectors are conserved across Y. pestis strains, but three - YopJ, YopT, and YpkA - are apparently dispensable for virulence. Some degree of functional redundancy between effector proteins would explain both observations. Here, we use a combinatorial genetic approach to define the minimal subset of effectors required for full virulence in mice following subcutaneous infection...
June 11, 2018: Infection and Immunity
Cecily R Wood, Emily J Ohneck, Richard E Edelmann, Luis A Actis
Transcriptional analyses of A. baumannii ATCC 17978 showed that the expression of A1S_2091 was enhanced in cells cultured in darkness at 24°C through a process that depended on the BlsA photoreceptor. Disruption of A1S_2091, a component of the A1S_2088-A1S_2091 polycistronic operon predicted to code for a type I chaperone/usher pilus assembly system, abolished surface motility and pellicle formation but significantly enhanced biofilm formation on plastic by bacteria cultured under darkness. Based on these observations, the A1S_2088-A1S_2091 operon was named the <u>p</u> hoto- <u>r</u> egulated <u>p</u> ilus ABCD ( prpABCD ) operon, with A1S_2091 coding for the PrpA pilin subunit...
June 11, 2018: Infection and Immunity
Yohsuke Ogawa, Kazumasa Shiraiwa, Sayaka Nishikawa, Masahiro Eguchi, Yoshihiro Shimoji
Erysipelothrix rhusiopathiae causes swine erysipelas, an infection characterized by acute septicemia or chronic endocarditis and polyarthritis. Among seventeen E. rhusiopathiae serovars, determined based on heat-stable peptidoglycan antigens, serovars 1 and 2 are most commonly associated with the disease; however, the molecular basis for the association between these serovars and virulence is unknown. To search for the genetic region defining serovar 1a (Fujisawa) strain antigenicity, we examined the 15-kb chromosomal region encompassing a putative pathway for polysaccharide biosynthesis, which was previously identified in the E...
June 11, 2018: Infection and Immunity
Steven C Kennedy, Alison J Johnson, Sushma Bharrhan, Cecilia S Lindestam Arlehamn, Jiayong Xu, Scott J Garforth, John Chan, William R Jacobs, Alessandro Sette, Steven C Almo, Steven A Porcelli
Mycobacterium tuberculosis remains a threat to global health, and a more efficacious vaccine is needed to prevent disease caused by Mtb. We previously reported that the mycobacterial ribosome is a major target of CD4+ T cells in mice immunized with a genetically modified M. smegmatis strain (IKEPLUS), but not in mice immunized with M bovis BCG. Two specific ribosomal proteins, RplJ and RpsA, were identified as cross-reactive targets of Mtb, but the breadth of the CD4+ T cell response to Mtb ribosomes was not determined...
June 11, 2018: Infection and Immunity
Yang Wang, Zhensong Wen, Xiaolei Pan, David E Briles, Yongqun He, Jing-Ren Zhang
The success of polysaccharide conjugate vaccines represents a major advance in the prevention of pneumococcal disease, but the power of these vaccines are limited by partial spectrum of coverage and high cost. Vaccines using immunoprotective proteins are a promising alternative type of pneumococcal vaccines. In this study, we constructed a library of antisera against conserved pneumococcal proteins predicted to be associated with cell surface or virulence, by a combination of bioinformatic prediction and immunization of rabbits with recombinant proteins...
June 11, 2018: Infection and Immunity
Ying-Han Lin, Yue Chen, Trever C Smith, S L Rajasekhar Karna, J Seshu
Borrelia burgdorferi (Bb ) responds to a variety of host-derived factors and appropriately alters its gene expression for adaptation under different host-specific conditions. We previously showed that varying levels of acetate, a <u>S</u>hort-<u>C</u>hain <u>F</u>atty <u>A</u>cid (SCFA), altered the protein profile of Bb In this study, we determined the effects of other physiologically relevant SCFAs in the regulation of metabolic/virulence-associated proteins using mutant borrelial strains...
June 11, 2018: Infection and Immunity
Chelsie E Armbruster, Sara N Smith, Lona Mody, Harry L T Mobley
Urinary tract infections (UTIs) are among the most common infections worldwide. Diagnosing UTIs in older adults poses a significant challenge as asymptomatic colonization is common. Identification of a non-invasive profile that predicts likelihood of progressing from urine colonization to severe disease would provide a significant advantage in clinical practice. We monitored colonization susceptibility, disease severity, and immune response to two uropathogens in two mouse strains across three age groups to identify predictors of infection outcome...
June 11, 2018: Infection and Immunity
Rima Tapader, Dipro Bose, Pujarini Dutta, Santasabuj Das, Amit Pal
SslE (YghJ), a cell surface associated and secreted lipoprotein was identified as a potential vaccine candidate for extraintestinal pathogenic E. coli providing nearly complete protection from sepsis in a mouse model. We earlier found that SslE from neonatal septicemic E. coli could trigger the secretion of various proinflammatory cytokines in murine macrophages, the signaling pathway of which is still obscure. In this study, we showed that SslE specifically binds to TLR2/TLR1 heterodimer and recruits downstream adaptors MyD88, TIRAP and TRAF6...
June 11, 2018: Infection and Immunity
Eileen A Wong, Louis Joslyn, Nicole L Grant, Edwin Klein, Philana Ling Lin, Denise E Kirschner, JoAnne L Flynn
The hallmarks of pulmonary Mycobacterium tuberculosis infection are lung granulomas. These organized structures are composed of host immune cells whose purpose is to contain or clear infection, creating a complex hub of immune and bacterial cell activity, as well as limiting pathology in the lungs. Yet, given cellular activity and potential for frequent interactions between host immune cells and Mtb infected cells, we observed a surprisingly low quantity of cytokine producing T cells (<10% of granuloma T cells) in our recent study of Mtb infection within non-human primate (NHP) granulomas...
June 11, 2018: Infection and Immunity
Alaa H Sewid, M Nabil Hassan, A M Ammar, David A Bemis, Stephen A Kania
Coagulase activation of prothrombin by staphylococcus induces the formation of fibrin deposition that facilitates the establishment of infection by Staphylococcus species. Coagulase activity is a key characteristic of Staphylococcus pseudintermedius , however, no coagulase gene or associated protein has been studied to characterize this activity. We report a recombinant protein sharing 40% similarity to Staphylococcus aureus coagulase produced from a putative S. pseudintermedius coagulase gene. Prothrombin activation by the protein was measured with a chromogenic assay using thrombin tripeptide substrate...
June 11, 2018: Infection and Immunity
Jeffrey S Bourgeois, Daoguo Zhou, Teresa L M Thurston, James J Gilchrist, Dennis C Ko
In order to deploy virulence factors at appropriate times and locations, microbes must rapidly sense and respond to various metabolite signals. Previously we showed transient elevation of the methionine-derived metabolite methylthioadenosine (MTA) in serum during systemic Salmonella enterica serovar Typhimurium ( S. Typhimurium) infection. Here we explored the functional consequences of increased MTA concentrations on S. Typhimurium virulence. We found that MTA-but not other related metabolites involved in polyamine synthesis and methionine salvage-reduced motility, host cell pyroptosis, and cellular invasion...
June 4, 2018: Infection and Immunity
Serena Giuntini, Matteo Stoppato, Maja Sedic, Monir Ejemel, Jessica R Pondish, Danielle Wisheart, Zachary A Schiller, William D Thomas, Eileen M Barry, Lisa A Cavacini, Mark S Klempner, Yang Wang
Background. Enterotoxigenic Escherichia coli (ETEC) cause diarrheal illness in infants in the developing world and travelers to endemic countries including military personnel. ETEC infection of the host involves colonization of the small intestinal epithelium and toxin secretion leading to watery diarrhea. There is currently no vaccine licensed to prevent ETEC. CFA/I is one of the most common colonization factor antigens (CFAs). The CFA/I adhesin subunit, CfaE, is required for ETEC adhesion to host intestinal cells...
June 4, 2018: Infection and Immunity
Sarah E Davis, Robert N Tams, Norma Solis, Andrew S Wagner, Tian Chen, Joseph W Jackson, Sahar Hasim, Anthony E Montedonico, Justin Dinsmore, Timothy E Sparer, Scott G Filler, Todd B Reynolds
Candida albicans mutants for phosphatidylserine (PS) synthase ( cho1 ΔΔ) and PS decarboxylase ( psd1 ΔΔ psd2 ΔΔ) are compromised for virulence in mouse models of systemic infection and oropharyngeal Candidiasis (OPC). Both of these enzymes are necessary to synthesize phosphatidylethanolamine (PE) by the de novo pathway, but these mutants are still capable of growth in culture media as they can import ethanolamine from media to synthesize PE through the Kennedy pathway. Given that the host has ethanolamine in its serum, the exact mechanism by which virulence is lost in these mutants is not clear...
June 4, 2018: Infection and Immunity
Dustin R Middleton, Amy V Paschall, Jeremy A Duke, Fikri Y Avci
Despite a century of investigation, Streptococcus pneumoniae ( Spn ) remains a major human pathogen, causing a number of diseases such as pneumonia, meningitis, and otitis media. Like many encapsulated pathogens, the capsular polysaccharide (CPS) of Spn is a critical component for colonization and virulence in mammalian hosts. This study aimed to evaluate the protective role of a glycoside hydrolase, Pn3Pase, targeting the CPS of type 3 Spn , which is one of the most virulent serotypes. We have assessed the ability of Pn3Pase to degrade the capsule on a live type 3 strain...
June 4, 2018: Infection and Immunity
Maliha Batool, Salvador Eugenio C Caoili, Lawrence J Dangott, Ekaterina Gerasimov, Yurij Ionov, Helen Piontkivska, Alex Zelikovsky, Suryakant D Waghela, Artem S Rogovskyy
The tick-borne pathogen, Borrelia burgdorferi , is responsible for approximately 300,000 Lyme disease (LD) cases per year in the United States. Recent increases in the number of LD cases in addition to the spread of the tick vector and a lack of vaccine highlights an urgent need for designing and developing an efficacious LD vaccine. Identification of protective epitopes that could be used to develop a second-generation vaccine is therefore imperative. Despite the antigenicity of several lipoproteins and integral outer membrane proteins (OMPs) on B...
June 4, 2018: Infection and Immunity
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