bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of Avidity of Antigen-Specific Antibody as a Means of Understanding Development of Long-Term Immunological Memory after Vibrio cholerae O1 Infection
Authors: Alam Mohammad Murshid , Arifuzzaman Mohammad , Ahmad Shaikh Meshbahuddin , Hosen M. Ismail , Rahman Mohammad Arif , Rashu Rasheduzzaman , Sheikh Alaullah , Ryan Edward T. , Calderwood Stephen B. , Qadri Firdausi 
Published: November 2012

ABSTRACTThe avidity of antibodies to specific antigens and the relationship of avidity to memory B cell responses to these antigens have not been studied in patients with cholera or those receiving oral cholera vaccines. We measured the avidity of antibodies to cholera toxin B subunit (CTB) andVibrio choleraeO1 lipopolysaccharide (LPS) in Bangladeshi adult cholera patients (n= 30), as well as vaccinees (n= 30) after administration of two doses of a killed oral cholera vaccine. We assessed antibody and memory B cell responses at the acute stage in patients or prior to vaccination in vaccinees and then in follow-up over a year. Both patients and vaccinees mounted CTB-specific IgG and IgA antibodies of high avidity. Patients showed longer persistence of these antibodies than vaccinees, with persistence lasting in patients up to day 270 to 360. The avidity of LPS-specific IgG and IgA antibodies in patients remained elevated up to 180 days of follow-up. Vaccinees mounted highly avid LPS-specific antibodies at day 17 (3 days after the second dose of vaccine), but the avidity waned rapidly to baseline by 30 days. We examined the correlation between antigen-specific memory B cell responses and avidity indices for both antigens. We found that numbers of CTB- and LPS-specific memory B cells significantly correlated with the avidity indices of the corresponding antibodies (P< 0.05; Spearman'sρ= 0.28 to 0.45). These findings suggest that antibody avidity after infection and immunization is a good correlate of the development and maintenance of memory B cell responses toVibrio choleraeO1 antigens.
Rational Design of Membrane Proximal External Region Lipopeptides Containing Chemical Modifications for HIV-1 Vaccination
Authors: Venditto Vincent J. , Watson Douglas S. , Motion Michael , Montefiori David , Szoka Francis C. 
Published: November 2012

ABSTRACT
The inability to generate broadly neutralizing antibody (bnAb) responses to the membrane proximal external region (MPER) of HIV-1 gp41 using current vaccine strategies has hampered efforts to prevent the spread of HIV. To address this challenge, we investigated a novel hypothesis to help improve the anti-MPER antibody response. Guided by structural insights and the unique lipid reactivity of anti-MPER bnAbs, we considered whether amino acid side chain modifications that emulate hydrophilic phospholipid head groups could contribute to the generation of 2F5-like or 4E10-like neutralizing anti-MPER antibodies. To test this hypothesis, we generated a series of chemically modified MPER immunogens through derivatization of amino acid side chains with phosphate or nitrate groups. We evaluated the binding affinity of the chemically modified peptides to their cognate monoclonal antibodies, 2F5 and 4E10, using surface plasmon resonance. The modifications had little effect on binding to the antibodies and did not influence epitope secondary structure when presented in liposomes. We selected five of the chemically modified sequences to immunize rabbits and found that an immunogen containing both the 2F5 and 4E10 epitopes and a phosphorylated threonine at T676 elicited the highest anti-peptide IgG titers, although the high antipeptide titers did not confer higher neutralizing activity. These data indicate that side chain modifications adjacent to known neutralizing antibody epitopes are capable of eliciting antibody responses to the MPER but that these chemically modified gp41 epitopes do not induce neutralizing antibodies.
Serologic Evidence of Pandemic Influenza Virus H1N1 2009 Infection in Cats in China
Authors: Su Shuo , Yuan Liguo , Li Huatao , Chen Jidang , Xie Jiexiong , Huang Zhen , Jia Kun , Li Shoujun 
Published: November 2012

ABSTRACT
Infection of domestic cats with (H1N1) pandemic 2009 (pdm09) influenza A virus has recently been documented. In this paper, we report for the first time the sporadically current seroprevalence of (H1N1) pdm09 influenza A virus infection in cats in China. Thirteen of 1,080 sera were found positive by nucleoprotein (NP)-specific enzyme-linked immunosorbent assays (ELISAs) in different cat populations in southern China. It is very important to stress further surveillance of pandemic (H1N1) 2009 influenza A virus in cats in southern China.
Increased Susceptibility of Melanin-Concentrating Hormone-Deficient Mice to Infection with Salmonella enterica Serovar Typhimurium
Authors: Karagiannis Apostolos K. A. , Ziogas Dimitrios C. , Gras-Miralles Beatriz , Geiger Brenda M. , Nagel Jutta , Trebicka Estela , Najarian Robert , Cherayil Bobby J. , Kokkotou Efi 
Published: November 2012

ABSTRACT

Melanin-concentrating hormone (MCH) was initially identified in mammals as a hypothalamic neuropeptide regulating appetite and energy balance. However, the wide distribution of MCH receptors in peripheral tissues suggests additional functions for MCH which remain largely unknown. We have previously reported that mice lacking MCH develop attenuated intestinal inflammation when exposed to
Clostridium difficile
toxin A. To further characterize the role of MCH in host defense mechanisms against intestinal pathogens,
Salmonella
enterocolitis (using
Salmonella enterica
serovar Typhimurium) was induced in MCH-deficient mice and their wild-type littermates. In the absence of MCH, infected mice had increased mortality associated with higher bacterial loads in blood, liver, and spleen. Moreover, the knockout mice developed more-severe intestinal inflammation, based on epithelial damage, immune cell infiltrates, and local and systemic cytokine levels. Paradoxically, these enhanced inflammatory responses in the MCH knockout mice were associated with disproportionally lower levels of macrophages infiltrating the intestine. Hence, we investigated potential direct effects of MCH on monocyte/macrophage functions critical for defense against intestinal pathogens. Using RAW 264.7 mouse monocytic cells, which express endogenous MCH receptor, we found that treatment with MCH enhanced the phagocytic capacity of these cells. Taken together, these findings reveal a previously unappreciated role for MCH in host-bacterial interactions.
Altered Toll-Like Receptor 9 Signaling in Mycobacterium avium subsp. paratuberculosis-Infected Bovine Monocytes Reveals Potential Therapeutic Targets
Authors: Arsenault Ryan J. , Li Yue , Maattanen Pekka , Scruten Erin , Doig Kimberley , Potter Andrew , Griebel Philip , Kusalik Anthony , Napper Scott 
Published: November 2012

ABSTRACTMycobacterium aviumsubsp.paratuberculosisis the causative agent of Johne's disease in cattle. The complex, multifaceted interaction ofM. aviumsubsp.paratuberculosiswith its host includes dampening the ability of infected cells to respond to stimuli that promoteM. aviumsubsp.paratuberculosisclearance. By disrupting host defenses,M. aviumsubsp.paratuberculosiscreates an intracellular environment that favors the establishment and maintenance of infection. Toll-like receptors (TLRs) are important sensors that initiate innate immune responses to microbial challenge and are also immunotherapeutic targets. For example, TLR9 contributes to host defense againstM. aviumsubsp.paratuberculosis, and its agonists (CpG oligodeoxynucleotides [ODNs]) are under investigation for treatment of Johne's disease and other infections. Here we demonstrate thatM. aviumsubsp.paratuberculosisinfection changes the responsiveness of bovine monocytes to TLR9 stimulation.M. aviumsubsp.paratuberculosisinhibits classical TLR9-mediated responses despite a 10-fold increase in TLR9 expression and maintained uptake of CpG ODNs. Other TLR9-mediated responses, such as oxidative burst, which occur through noncanonical signaling, remain functional. Kinome analysis verifies that classic TLR9 signaling is blocked byM. aviumsubsp.paratuberculosisinfection and that signaling instead proceeds through a Pyk2-mediated mechanism. Pyk2-mediated signaling does not hinder infection, as CpG ODNs fail to promoteM. aviumsubsp.paratuberculosisclearance. Indeed, Pyk2 signaling appears to be an important aspect ofM. aviumsubsp.paratuberculosisinfection, as Pyk2 inhibitors significantly reduce the number of intracellularM. aviumsubsp.paratuberculosisbacteria. The actions ofM. aviumsubsp.paratuberculosison TLR9 signaling may represent a strategy to generate a host environment which is better suited for infection, revealing potential new targets for therapeutic intervention.
Adenylate Cyclase and the Cyclic AMP Receptor Protein Modulate Stress Resistance and Virulence Capacity of Uropathogenic Escherichia coli
Authors: Donovan Grant T. , Norton J. Paul , Bower Jean M. , Mulvey Matthew A. 
Published: November 2012

ABSTRACTIn many bacteria, the second messenger cyclic AMP (cAMP) interacts with the transcription factor cAMP receptor protein (CRP), forming active cAMP-CRP complexes that can control a multitude of cellular activities, including expanded carbon source utilization, stress response pathways, and virulence. Here, we assessed the role of cAMP-CRP as a regulator of stress resistance and virulence in uropathogenicEscherichia coli(UPEC), the principal cause of urinary tract infections worldwide. Deletion of genes encoding either CRP or CyaA, the enzyme responsible for cAMP synthesis, attenuates the ability of UPEC to colonize the bladder in a mouse infection model, dependent on intact innate host defenses. UPEC mutants lacking cAMP-CRP grow normally in the presence of glucose but are unable to utilize alternate carbon sources like amino acids, the primary nutrients available to UPEC within the urinary tract. Relative to the wild-type UPEC isolate, thecyaAandcrpdeletion mutants are sensitive to nitrosative stress and the superoxide generator methyl viologen but remarkably resistant to hydrogen peroxide (H2O2) and acid stress. In the mutant strains, H2O2resistance correlates with elevated catalase activity attributable in part to enhanced translation of the alternate sigma factor RpoS. Acid resistance was promoted by both RpoS-independent and RpoS-dependent mechanisms, including expression of the RpoS-regulated DNA-binding ferritin-like protein Dps. We conclude that balanced input from many cAMP-CRP-responsive elements, including RpoS, is critical to the ability of UPEC to handle the nutrient limitations and severe environmental stresses present within the mammalian urinary tract.
Beclin 1 Is Required for Starvation-Enhanced, but Not Rapamycin-Enhanced, LC3-Associated Phagocytosis of Burkholderia pseudomallei in RAW 264.7 Cells
Authors: Li Xuelei , Prescott Mark , Adler Ben , Boyce John D. , Devenish Rodney J. 
Published: November 2012

ABSTRACT

LC3-associated phagocytosis (LAP) of
Burkholderia pseudomallei
by murine macrophage (RAW 264.7) cells is an intracellular innate defense mechanism. Beclin 1, a protein with several roles in autophagic processes, is known to be recruited to phagosomal membranes as a very early event in LAP. We sought to determine whether knockdown of Beclin 1 by small interfering RNA (siRNA) would affect recruitment of LC3 and subsequent LAP of infecting
B. pseudomallei
. Both starvation and rapamycin treatment can induce Beclin 1-dependent autophagy. Therefore, we analyzed the consequences of Beclin 1 knockdown for LAP in infected cells that had been either starved or treated with rapamycin by determining the levels of bacterial colocalization with LC3 and intracellular survival. Concurrently, we confirmed the location of bacteria as either contained in phagosomes or free in the cytoplasm. We found that both rapamycin and starvation treatment enhanced LAP of
B. pseudomallei
but that the rapamycin response is Beclin 1 independent whereas the starvation response is Beclin 1 dependent.
Use of Site-Directed Mutagenesis To Model the Effects of Spontaneous Deamidation on the Immunogenicity of Bacillus anthracis Protective Antigen
Authors: Verma Anita , McNichol Beth , Domínguez-Castillo Rocío I. , Amador-Molina Juan C. , Arciniega Juan L. , Reiter Karine , Meade Bruce D. , Ngundi Miriam M. , Stibitz Scott , Burns Drusilla L. 
Published: November 2012

ABSTRACT
Long-term stability is a desired characteristic of vaccines, especially anthrax vaccines, which must be stockpiled for large-scale use in an emergency situation; however, spontaneous deamidation of purified vaccine antigens has the potential to adversely affect vaccine immunogenicity over time. In order to explore whether spontaneous deamidation of recombinant protective antigen (rPA)—the major component of new-generation anthrax vaccines—affects vaccine immunogenicity, we created a “genetically deamidated” form of rPA using site-directed mutagenesis to replace six deamidation-prone asparagine residues, at positions 408, 466, 537, 601, 713, and 719, with either aspartate, glutamine, or alanine residues. We found that the structure of the six-Asp mutant rPA was not significantly altered relative to that of the wild-type protein as assessed by circular dichroism (CD) spectroscopy and biological activity. In contrast, immunogenicity of aluminum-adjuvanted six-Asp mutant rPA, as measured by induction of toxin-neutralizing antibodies, was significantly lower than that of the corresponding wild-type rPA vaccine formulation. The six-Gln and six-Ala mutants also exhibited lower immunogenicity than the wild type. While the wild-type rPA vaccine formulation exhibited a high level of immunogenicity initially, its immunogenicity declined significantly upon storage at 25°C for 4 weeks. In contrast, the immunogenicity of the six-Asp mutant rPA vaccine formulation was low initially but did not change significantly upon storage. Taken together, results from this study suggest that spontaneous deamidation of asparagine residues predicted to occur during storage of rPA vaccines would adversely affect vaccine immunogenicity and therefore the storage life of vaccines.
Enterococcus faecalis Inhibits Hyphal Morphogenesis and Virulence of Candida albicans
Authors: Cruz Melissa R. , Graham Carrie E. , Gagliano Bryce C. , Lorenz Michael C. , Garsin Danielle A. 
Published: November 2012

ABSTRACTThe Gram-positive bacteriumEnterococcus faecalisand the fungusCandida albicansare both found as commensals in many of the same niches of the human body, such as the oral cavity and gastrointestinal (GI) tract. However, both are opportunistic pathogens and have frequently been found to be coconstituents of polymicrobial infections. Despite these features in common, there has been little investigation into whether these microbes affect one another in a biologically significant manner. Using aCaenorhabditis elegansmodel of polymicrobial infection, we discovered thatE. faecalisandC. albicansnegatively impact each other's virulence. Much of the negative effect ofE. faecalisonC. albicanswas due to the inhibition ofC. albicanshyphal morphogenesis, a developmental program crucial toC. albicanspathogenicity. We discovered that the inhibition was partially dependent on the Fsr quorum-sensing system, a major regulator of virulence inE. faecalis. Specifically, two proteases regulated by Fsr, GelE and SerE, were partially required. Further characterization of the inhibitory signal revealed that it is secreted into the supernatant, is heat resistant, and is between 3 and 10 kDa. The substance was also shown to inhibitC. albicansfilamentation in the context of anin vitrobiofilm. Finally, a screen of anE. faecalistransposon mutant library identified other genes required for suppression ofC. albicanshyphal formation. Overall, we demonstrate a biologically relevant interaction between two clinically important microbes that could affect treatment strategies as well as impact our understanding of interkingdom signaling and sensing in the human-associated microbiome.
Identification and Characterization of the First Cholesterol-Dependent Cytolysins from Gram-Negative Bacteria
Authors: Hotze Eileen M. , Le Huynh M. , Sieber Jessica R. , Bruxvoort Christina , McInerney Michael J. , Tweten Rodney K. 
Published: November 2012

ABSTRACTThe cholesterol-dependent cytolysins (CDCs) are pore-forming toxins that have been exclusively associated with a wide variety of bacterial pathogens and opportunistic pathogens from theFirmicutesandActinobacteria, which exhibit a Gram-positive type of cell structure. We have characterized the first CDCs from Gram-negative bacterial species, which includeDesulfobulbus propionicustype species Widdel 1981 (DSM 2032) (desulfolysin [DLY]) andEnterobacter lignolyticus(formerlyEnterobacter cloacae) SCF1 (enterolysin [ELY]). The DLY and ELY primary structures show that they maintain the signature motifs of the CDCs but lack an obvious secretion signal. Recombinant, purified DLY (rDLY) and ELY (rELY) exhibited cholesterol-dependent binding and cytolytic activity and formed the typical large CDC membrane oligomeric pore complex. Unlike the CDCs from Gram-positive species, which are human- and animal-opportunistic pathogens, neitherD. propionicusnorE. lignolyticusis known to be a pathogen or commensal of humans or animals: the habitats of both organisms appear to be restricted to anaerobic soils and/or sediments. These studies reveal for the first time that the genes for functional CDCs are present in bacterial species that exhibit a Gram-negative cell structure. These are also the first bacterial species containing a CDC gene that are not known to inhabit or cause disease in humans or animals, which suggests a role of these CDCs in the defense against eukaryote bacterial predators.
Growth of Candida albicans Cells on the Physiologically Relevant Carbon Source Lactate Affects Their Recognition and Phagocytosis by Immune Cells
Authors: Ene Iuliana V. , Cheng Shih-Chin , Netea Mihai G. , Brown Alistair J. P. 
Published: November 2012

ABSTRACTCandida albicansis a normal resident of the human gastrointestinal and urogenital tracts and also a prevalent fungal pathogen. During both commensalism and infection, it must match the immunological defenses of its host while adapting to environmental cues and the local nutrient status.C. albicansregularly colonizes glucose-poor niches, thereby depending upon alternative carbon sources for growth. However, most studies of host immune responses toC. albicanshave been performed on fungal cells grown on glucose, and the extent to which alternative physiologically relevant carbon sources impact innate immune responses has not been studied. The fungal cell wall is decorated with multifarious pathogen-associated molecular patterns and is the main target for recognition by host innate immune cells. Cell wall architecture is both robust and dynamic, and it is dramatically influenced by growth conditions. We found that growth ofC. albicanscells on lactate, a nonfermentative carbon source available in numerous anatomical niches, modulates their interactions with immune cells and the resultant cytokine profile. Notably, lactate-grownC. albicansstimulated interleukin-10 (IL-10) production while decreasing IL-17 levels, rendering these cells less visible to the immune system than were glucose-grown cells. This trend was observed in clinicalC. albicansisolates from different host niches and from different epidemiological clades. In addition, lactate-grownC. albicanscells were taken up by macrophages less efficiently, but they were more efficient at killing and escaping these phagocytic cells. Our data indicate that carbon source has a major impact upon theC. albicansinteraction with the innate immune system.
Using Major Outer Membrane Protein Typing as an Epidemiological Tool To Investigate Outbreaks Caused by Milk-Borne Campylobacter jejuni Isolates in California
Authors: Jay-Russell Michele T. , Mandrell Robert E. , Yuan Jean , Bates Anna , Manalac Rosa , Mohle-Boetani Janet , Kimura Akiko , Lidgard Janice , Miller William G. 
Published: November 2012

ABSTRACT

We describe using major outer membrane protein (MOMP) typing as a screen to compare the
Campylobacter jejuni porA
gene sequences of clinical outbreak strains from human stool with the
porA
sequences of dairy farm strains isolated during two milk-borne campylobacteriosis outbreak investigations in California. The genetic relatedness of clinical and environmental strains with identical or closely related
porA
sequences was confirmed by multilocus sequence typing and pulsed-field gel electrophoresis analysis. The first outbreak involved 1,644
C. jejuni
infections at 11 state correctional facilities and was associated with consumption of pasteurized milk supplied by an on-site dairy (dairy A) at a prison in the central valley. The second outbreak involved eight confirmed and three suspect
C. jejuni
cases linked to consumption of commercial raw milk and raw chocolate colostrum at another central valley dairy (dairy B). Both dairies bottled fluid milk on the farm and distributed the finished product to off-site locations. Altogether,
C. jejuni
was isolated from 7 of 15 (46.7%) bovine fecal, 12 of 20 (60%) flush alley water, and 1 of 20 (5%) lagoon samples collected on dairy A. At dairy B,
C. jejuni
was cultured from 9 of 26 (34.6%) bovine fecal samples. Environmental strains indistinguishable from the clinical outbreak strains were found in five flush alley water samples (dairy A) and four bovine fecal samples (dairy B). The findings demonstrate that MOMP typing is a useful tool to triage environmental isolates prior to conducting more labor-intensive molecular typing methods.
Global Phylogeny of Shigella sonnei Strains from Limited Single Nucleotide Polymorphisms (SNPs) and Development of a Rapid and Cost-Effective SNP-Typing Scheme for Strain Identification by High-Resolution Melting Analysis
Authors: Sangal Vartul , Holt Kathryn E. , Yuan Jianfeng , Brown Derek J. , Filliol-Toutain Ingrid , Weill François-Xavier , Kim Dong-Wook , da Silveira Wanderley Dias , Pickard Derek , Thomson Nicholas R. , Parkhill Julian , Yu Jun 
Published: November 2012

ABSTRACT

The current
Shigella sonnei
pandemic involves geographically associated, multidrug-resistant clones. This study has demonstrated that
S. sonnei
phylogeny can be accurately defined with limited single nucleotide polymorphisms (SNPs). By typing 6 informative SNPs using a high-resolution melting (HRM) assay, major
S. sonnei
lineages/sublineages can be identified as defined by whole-genome variation.
Acute Right-Sided Heart Failure Caused by Neisseria meningitidis
Authors: Taldir Guillaume , Parize Perrine , Arvis Philippe , Faisy Christophe 
Published: November 2012

ABSTRACT

Meningococcal myocarditis is a rarely diagnosed infection and could be the consequence of primary invasive infection or late immunologic complications. An unusual presentation of meningococcemia in an immunocompetent adult is described, with
Neisseria meningitidis
identified as the cause of selective right-sided heart failure in a case of acute myocarditis.