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Infection and Immunity

Lillian J Juttukonda, Erin R Green, Zachery R Lonergan, Marie C Heffern, Christopher J Chang, Eric P Skaar
Acinetobacter baumannii is a Gram-negative opportunistic pathogen that causes diverse infections, including pneumonia, bacteremia, and wound infections. Due to multiple intrinsic and acquired antimicrobial-resistance mechanisms, A. baumannii isolates are commonly multi-drug resistant and infections are notoriously difficult to treat. The World Health Organization recently highlighted carbapenem-resistant A. baumannii as a 'critical priority' for the development of new antimicrobials because of the risk to human health posed by this organism...
October 8, 2018: Infection and Immunity
Jeremy Bechelli, Leoncio Vergara, Claire Smalley, Tetyana P Buzhdygan, Sean Bender, William Zhang, Yan Liu, Vsevolod L Popov, Jin Wang, Nisha Garg, Seungmin Hwang, David H Walker, Rong Fang
Rickettsiae can cause life-threatening infections in humans. Macrophages are one of the initial targets for rickettsiae after inoculation by ticks. However, it remains poorly understood how rickettsiae remain free in macrophages prior to establishing their infection in microvascular endothelial cells. Here, we demonstrated that the concentration of Rickettsia australis was significantly greater in infected tissues of Atg5flox/flox mice compared to the counterparts of Atg5flox/flox Lyz- Cre mice, in association with a reduced level of IL-1β in serum...
October 8, 2018: Infection and Immunity
David R Danforth, Gaoyan Tang-Siegel, Teresa Ruiz, Keith P Mintz
Periodontitis is an inflammatory disease caused by polymicrobial biofilms. The periodontal pathogen Aggregatibacter actinomycetemcomitans displays two proteinaceous surface structures, the fimbriae and the non-fimbrial extracellular matrix binding protein A (EmaA), as observed by electron microscopy. Fimbriae participate in biofilm biogenesis and the EmaA adhesins mediate collagen binding. However, in the absence of fimbriae, A. actinomycetemcomitans still retains the potential to form robust biofilms, suggesting other surface macromolecules participate in biofilm development...
October 8, 2018: Infection and Immunity
Mauricio A Navarro, Jihong Li, Bruce A McClane, Eleonora Morrell, Juliann Beingesser, Francisco A Uzal
Clostridium perfringens type F (formerly enterotoxigenic C. perfringens type A) strains produce an enterotoxin (CPE) to cause acute cases of food poisoning and chronic nonfoodborne human gastrointestinal diseases (NFD), e.g. antibiotic-associated diarrhea (AAD). NFD strains produce NanI sialidase, an extracellular enzyme that releases sialic acids from sialyated host macromolecules. Recent in vitro studies suggested that NanI may contribute to NFD strain intestinal colonization by enhancing their adherence to intestinal cells and promoting their bacterial growth using generated sialic acid as an energy source...
October 8, 2018: Infection and Immunity
Alison Coady, Anissa R Ramos, Joshua Olson, Victor Nizet, Kathryn A Patras
Urinary tract infections (UTIs) caused by the human fungal pathogen Candida albicans and related species are prevalent in hospitalized patients, especially those on antibiotic therapy, with indwelling catheters, or with predisposing conditions such as diabetes or immunodeficiency. Understanding of key host defenses against Candida UTI are critical for developing effective treatment strategies. Tamm-Horsfall glycoprotein (THP) is the most abundant urine protein with multiple roles in renal physiology and bladder protection...
October 8, 2018: Infection and Immunity
M Carmen Herrero-Sánchez, Eduardo B Angomás, Cristina de Ramón, Juan J Tellería, Luis A Corchete, Sara Alonso, M Del Carmen Ramos, María J Peñarrubia, Saioa Márquez, Nieves Fernández, Luis J García Frade, Mariano Sánchez Crespo
High-risk hematologic malignancies are a privileged setting for infection by opportunistic microbes, invasive mycoses being one of the most serious complications. Recently, the genetic background has emerged as an unanticipated risk factor. For this reason, polymorphisms for genes encoding archetypal receptors involved in the opsonic and non-opsonic clearance of microbes, pentraxin-3, and Dectin-1, respectively, were studied and correlated with the risk of infection. Fungal, bacterial, and viral infections were registered in a group of 198 patients with high-risk hematologic malignancies...
October 1, 2018: Infection and Immunity
Melissa Govender, Ramona Hurdayal, Berenice Martinez Salazar, Kaya Gqada, Shandre Pillay, Lorna Gcanga, Katiuska Passelli, Natalie E Nieuwenhuizen, Fabienne Tacchini-Cottier, Reto Guler, Frank Brombacher
The skin microenvironment at the site of infection plays a role in the early events that determine protective T helper 1/type 1 immune responses during cutaneous leishmaniasis (CL) infection. During CL in non-healing BALB/c mice, early Interleukin (IL)-4 can instruct dendritic cells for protective Th1 immunity. Additionally, keratinocytes, which are the principal cell-type in the skin epidermis, have been shown to secrete IL-4 early after Leishmania major infection. Here, we investigated whether IL-4/IL-13 signalling via the common IL-4 receptor alpha chain (IL-4Rα) on keratinocytes may contribute to susceptibility during experimental CL...
October 1, 2018: Infection and Immunity
Courtney L Luterbach, Harry L T Mobley
The MarR-like protein PapX represses transcription of the flagellar master regulator genes flhDC in uropathogenic Escherichia coli (UPEC), the primary cause of uncomplicated urinary tract infections (UTIs). PapX is encoded by the pap operon, which also encodes the adherence factor P fimbriae. Both adherence and motility are critical for productive colonization of the urinary tract. However, the mechanisms involved in coordinating the transition between adherence and motility are not well characterized. The UPEC strain CFT073 carries both papX and a homolog focX , located in the foc operon encoding F1C fimbriae...
October 1, 2018: Infection and Immunity
Irvin Oh, Gowrishankar Muthukrishnan, Mark J Ninomiya, James D Brodell, Benjamin L Smith, Charles C Lee, Steven R Gill, Christopher A Beck, Edward M Schwarz, John L Daiss
Management of foot salvage therapy (FST) for diabetic foot infections (DFI) is challenging due to the absence of reliable diagnostics to identify the etiologic agent, and prognostics to justify aggressive treatments. As Staphylococcus aureus is the most common pathogen associated with DFI, we aimed to develop a multiplex immunoassay of IgG in serum, and medium enriched for newly synthesized anti- S. aureus antibodies (MENSA) generated from cultured peripheral blood mononuclear cells of DFI patients undergoing FST...
October 1, 2018: Infection and Immunity
Kyung Won Lee, Minseok Kim, Chang Hoon Lee
Disruption of the healthy intestinal microbiome and homeostasis of the intestinal immune system, which are closely interactive are two key factors for ulcerative colitis. Here, we show that MI-2, a selective inhibitor of mucosal-associated lymphoid tissue lymphoma translocation-1 (MALT1), alleviated excessive inflammatory responses and was associated with restoration of healthy intestinal microbiome in dextran sulfate sodium (DSS)-induced colitis mice. We found that the diversity of intestinal microbiome of DSS-induced colitis mice was significantly lower than that of healthy mice...
September 24, 2018: Infection and Immunity
Bing Pang, Chelsie E Armbruster, Gayle Foster, Brian S Learman, Uma Gandhi, W Edward Swords
Nontypeable Haemophilus influenzae (NT Hi ) is an extremely common human pathobiont that persists on the airway mucosal surface within biofilm communities, and our prior work has shown that NT Hi biofilm maturation is coordinated by production and uptake of AI-2 quorum signals. To directly test roles for AI-2 in maturation and maintenance of NT Hi biofilms, we generated an NT Hi 86-028NP mutant in which luxS transcription was under control of the xylA promoter (NT Hi 86-028NP luxS xylA :: luxS ), rendering AI-2 production inducible by xylose...
September 24, 2018: Infection and Immunity
Ellen E Higginson, Girish Ramachandran, Aruna Panda, Steven T Shipley, Edwin H Kriel, Louis J DeTolla, Michael Lipsky, Darren J Perkins, Rosangela Salerno-Goncalves, Marcelo B Sztein, Marcela F Pasetti, Myron M Levine, Sharon M Tennant
A notable proportion of Salmonella -associated gastroenteritis in the United States is attributed to Salmonella enterica serovar Typhimurium. We have previously shown that live-attenuated S. Typhimurium vaccine candidate CVD 1921 (I77 Δ guaBA Δ clpP ) was safe and immunogenic in rhesus macaques, but was shed for an undesirably long time post-immunization. In mice, occasional mortality post-vaccination was also noted (approximately 1 in every 15 mice). Herein we describe a further attenuated vaccine candidate strain harboring deletions in two additional genes, htrA and pipA We determined that S...
September 24, 2018: Infection and Immunity
Cortney E Heim, Sean C West, Hesham Ali, Tammy Kielian
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature monocytes and granulocytes. While neutrophils (PMNs) are classically identified as highly differentiated cells specialized for anti-microbial defense, our laboratory has reported minor contributions of PMNs to the immune response during S. aureus biofilm infection. However, these two cell types can be difficult to differentiate because of shared surface marker expression. Here we describe a more refined approach to distinguish MDSCs from PMNs utilizing the integrin receptor CD11b combined with conventional Ly6G and Ly6C expression...
September 24, 2018: Infection and Immunity
Ornella Salvatori, Ruvini U Pathirana, Jason G Kay, Mira Edgerton
Host phagocytic cells are crucial players in initial defense against Candida albicans infection. C. albicans utilizes MAP Kinases and Ras1 stress response signaling pathways to protect itself from killing by immune cells. In this study we tested the importance of these pathways on C. albicans phagocytosis by neutrophils and subsequent phagosomal survival. Phagocytosis was influenced by C. albicans morphology, so that hyphal length > 10 μm reduced the phagocytic index (PI) by 2-3 fold in human neutrophils...
September 24, 2018: Infection and Immunity
Dhrubajyoti Nag, Paul Breen, Saumya Raychaudhuri, Jeffrey H Withey
The V. cholerae O1 serogroup is responsible for pandemic cholera and is divided into the classical and El Tor biotypes. Classical V. cholerae produces acid when using glucose as a carbon source, whereas El Tor V. cholerae produces the neutral product acetoin when using glucose as a carbon source. An earlier study demonstrated that Escherichia coli strains that metabolize glucose to acidic by-products drastically reduced the survival of V. cholerae strains in vitro. In the present study, zebrafish were fed 1% glucose and inoculated with single V...
September 24, 2018: Infection and Immunity
Jill E Weatherhead, Paul Porter, Amy Coffey, Dana Haydel, Leroy Versteeg, Bin Zhan, Ana Clara Gazzinelli Guimarães, Ricardo Fujiwara, Ana M Jaramillo, Maria Elena Bottazzi, Peter J Hotez, David B Corry, Coreen M Beaumier
INTRODUCTION: Ascaris lumbricoides (roundworm) is the most common helminth infection globally and a cause of life-long morbidity that may include allergic airway disease, an asthma phenotype. We hypothesize that Ascaris larval migration through the lungs leads to persistent airway hyperresponsiveness (AHR) and type-2 inflammatory lung pathology despite resolution of infection that resembles allergic airway disease. MATERIALS AND METHODS: Mice were infected with Ascaris by oral gavage...
September 24, 2018: Infection and Immunity
Hubertine M E Willems, David J Lowes, Katherine S Barker, Glen E Palmer, Brian M Peters
The human fungal pathogen Candida albicans is the major etiological agent of vulvovaginal candidiasis (VVC). Despite this fact, other non- albicans Candida (NAC) species have frequently been reported as well. Despite their presence in the vaginal environment, little is known about their capacity to elicit immune responses classically associated with C. albicans -mediated immunopathology, including neutrophil recruitment and pro-inflammatory cytokine signaling. Therefore, using a combination of in vitro and in vivo approaches, we undertook a comparative analysis to determine whether a representative panel of NAC species could colonize, induce immunopathological markers, or cause damage at the vaginal mucosa...
September 24, 2018: Infection and Immunity
Rajrupa Chakraborty, Vy Lam, Sushma Kommineni, Jeremiah Stromich, Michael Hayward, Christopher J Kristich, Nita H Salzman
Enterococci are Gram-positive commensals of the mammalian intestinal tract and harbor intrinsic resistance to broad-spectrum cephalosporins. Disruption of colonization resistance in humans by antibiotics allow enterococci to proliferate in the gut and cause disseminated infections. In this study, we used Enterococcus faecalis (EF) colonized mice to study the dynamics of enterococci, commensal microbiota and host in response to systemic ceftriaxone administration. We found that the mouse model recapitulates intestinal proliferation and dissemination of enterococci seen in humans...
September 17, 2018: Infection and Immunity
Mark A Rodgers, Cassaundra Ameel, Amy L Ellis-Connell, Alexis J Balgeman, Pauline Maiello, Gabrielle L Barry, Thomas C Friedrich, Edwin Klein, Shelby L O'Connor, Charles A Scanga
Tuberculosis (TB), caused by Mycobacterium tuberculosis ( M.tb ), is the leading cause of death among HIV positive patients. The precise mechanisms by which HIV impairs host resistance to a subsequent M.tb infection are unknown. We modeled this co-infection in Mauritian cynomolgus macaques (MCM) using SIV as an HIV surrogate. We infected seven MCM with SIVmac239 intrarectally and six months later co-infected them via bronchoscope with ∼10 CFU M.tb Another eight MCM were infected with M.tb alone. TB progression was monitored by clinical parameters, by culturing bacilli in gastric and bronchoalveolar lavages, and by serial 18 F-FDG PET/CT imaging...
September 17, 2018: Infection and Immunity
Suba Nookala, Santhosh Mukundan, Alexander Fife, Jeyashree Alagarsamy, Malak Kotb
Invasive Group A Streptococcus (GAS) infections include necrotizing soft tissue infections (NSTI) and streptococcal toxic shock syndrome (STSS). We have previously shown that host HLA class-II allelic variations determine the risk for necrotizing fasciitis (NF), a dominant subgroup of NSTI, and STSS by modulating responses to GAS superantigens (SAgs). SAgs are pivotal mediators of uncontrolled T-cell activation, triggering a pro-inflammatory cytokine storm in the host. FoxP3-expressing CD4+ CD25+ T-regulatory cells (Tregs) comprise phenotypically and functionally heterogeneous subsets with a profound ability to suppress inflammatory responses...
September 17, 2018: Infection and Immunity
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