Abstract:
:The orotidine-5'-monophosphate decarboxylase (OMPDC) gene, encoding the final enzyme of the de novo pyrimidine biosynthesis pathway, was deleted using Toxoplasma gondii KU80 knockouts to develop an avirulent nonreverting pyrimidine auxotroph strain. Additionally, to functionally address the role of the pyrimidine salvage pathway, the uridine phosphorylase (UP) salvage activity was knocked out and a double knockout of UP and OMPDC was also constructed. The nonreverting DeltaOMPDC, DeltaUP, and DeltaOMPDC DeltaUP knockout strains were evaluated for pyrimidine auxotrophy, for attenuation of virulence, and for their ability to elicit potent immunity to reinfection. The DeltaUP knockout strain was replication competent and virulent. In contrast, the DeltaOMPDC and DeltaOMPDC DeltaUP strains were uracil auxotrophs that rapidly lost their viability during pyrimidine starvation. Replication of the DeltaOMPDC strain but not the DeltaOMPDC DeltaUP strain was also partially rescued in vitro with uridine or cytidine supplementation. Compared to their hypervirulent parental type I strain, the DeltaOMPDC and DeltaOMPDC DeltaUP knockout strains exhibited extreme attenuation in murine virulence (approximately 8 logs). Genetic complementation of the DeltaOMPDC strain using a functional OMPDC allele restored normal replication and type I parental strain virulence phenotypes. A single immunization of mice with either the live critically attenuated DeltaOMPDC strain or the DeltaOMPDC DeltaUP knockout strain effectively induced potent protective immunity to lethal challenge infection. The avirulent nonreverting DeltaOMPDC and DeltaOMPDC DeltaUP strains provide new tools for the dissection of the host response to infection and are promising candidates for safe and effective Th1 vaccine platforms that can be easily genetically engineered.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Fox BA,Bzik DJdoi
10.1128/IAI.00287-10subject
Has Abstractpub_date
2010-09-01 00:00:00pages
3744-52issue
9eissn
0019-9567issn
1098-5522pii
IAI.00287-10journal_volume
78pub_type
杂志文章abstract::While gamma/delta T cells are involved in host defense and immunopathology in a variety of infectious diseases, their precise role is not yet clearly defined. In the absence of gamma/delta T cells, mice die after infection with a dose of Listeria monocytogenes that is not lethal in immunologically intact animals. Morb...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.12.7213-7223.2001
更新日期:2001-12-01 00:00:00
abstract::Insertional mutagenesis studies of mrpB, a putative pilin-encoding open reading frame of the mrp gene cluster, which encodes mannose-resistant Proteus-like (MR/P) fimbriae of Proteus mirabilis, indicate that MrpB functions as the terminator for fimbrial assembly. ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.66.4.1759-1763.1998
更新日期:1998-04-01 00:00:00
abstract::Human lactoferrin is an iron-binding glycoprotein that is particularly prominent in exocrine secretions and leukocytes and is also found in serum, especially during inflammation. It is able to sequester iron from microbes and has immunomodulatory functions, including inhibition of both complement activation and cytoki...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.5.3372-3381.2001
更新日期:2001-05-01 00:00:00
abstract::The cyst cell wall β-glucans of Pneumocystis have been shown to stimulate immune responses in lung epithelial cells, dendritic cells, and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with these innate immune cells. Here, we report differences in...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00519-16
更新日期:2016-11-01 00:00:00
abstract::A recombinant 23-kDa protein (rBPI23) derived from human bactericidal/permeability-increasing protein (BPI) possesses potent endotoxin-neutralizing abilities in vitro and in vivo. Binding of rBPI23 to those endotoxins (lipopolysaccharides [LPSs]) encountered clinically would be a prerequisite for efficacy in decreasin...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.62.8.3564-3567.1994
更新日期:1994-08-01 00:00:00
abstract::Experimental Helicobacter pylori infection was studied in Mongolian gerbils with fresh human isolates that carry or do not carry cagA (cagA-positive or cagA-negative, respectively), multiply passaged laboratory strains, wild-type strain G1.1, or isogenic ureA, cagA, or vacA mutants of G1.1. Animals were sacrificed 1 t...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.66.10.4856-4866.1998
更新日期:1998-10-01 00:00:00
abstract::The two published sequences of the pertussis toxin operon differ in 3 bp in the S1 subunit gene. In this report, we provide evidence that Bordetella pertussis strains are able to produce active pertussis toxin only when they contain one of the two possible nucleotide sequences. ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.59.3.1177-1179.1991
更新日期:1991-03-01 00:00:00
abstract::Spotted fever group rickettsiae are known to produce distinct plaque phenotypes. Strains that cause lytic infections in cell culture form clear plaques, while nonlytic strains form opaque plaques in which the cells remain intact. Clear plaques have historically been associated with more-virulent species or strains of ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00048-11
更新日期:2011-04-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.12.7374-7379.2001
更新日期:2001-12-01 00:00:00
abstract::Intracellular survival of Chlamydia psittaci is in part dependent on the ability of the organism to thwart phagolysosome formation. Circumvention of phagolysosome fusion could be either localized to chlamydia-laden vacuoles or generalized to all phagosomes in the host cell. To determine which of these modes is in oper...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.32.2.889-896.1981
更新日期:1981-05-01 00:00:00
abstract::Although cryptococcosis is characterized as a chronic central nervous system disease, it is generally accepted that the lungs are the primary portal of entry for the etiological agent. Despite this, there is a distinct lack of evidence that viable airborne particles of Cryptococcus neoformans are small enough to reach...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.17.3.634-638.1977
更新日期:1977-09-01 00:00:00
abstract::Polymicrobial intra-abdominal infections (IAIs) are a significant cause of morbidity and mortality, particularly when fungal pathogens are involved. Our experimental murine model of IAI involving intraperitoneal inoculation of Candida albicans and Staphylococcus aureus results in synergistic lethality (∼80%) due to ex...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00144-18
更新日期:2018-06-21 00:00:00
abstract::Antibodies directed against Pfs25, a protein present on the surface of zygotes and ookinetes of Plasmodium falciparum, completely block pathogen transmission. We evaluated the immunomodulatory effect of CpG oligodeoxynucleotides (ODN) on the immunogenicity of recombinant Pfs25 (rPfs25) formulated in alum (Al). Immuniz...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.72.1.584-588.2004
更新日期:2004-01-01 00:00:00
abstract::Escherichia coli isolates from patients with bacteriuria of pregnancy were compared by PCR with isolates from patients with community-acquired cystitis for the presence of established virulence determinants. The strains from patients with bacteriuria of pregnancy were less likely to carry genes for P-family, S-family,...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.2.794-799.2001
更新日期:2001-02-01 00:00:00
abstract::Salmonella pathogenicity island 12 (SPI-12) of Salmonella enterica serovar Typhimurium is a 15-kb region that encompasses genes STM2230 to STM2245 and encodes a remnant phage known to contribute to bacterial virulence. In mouse infection experiments and replication assays in macrophages, we demonstrated a role for fou...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00067-13
更新日期:2013-07-01 00:00:00
abstract::Encapsulated Streptococcus pneumoniae of serotypes 2, 9N, 14, 21, and 23F and an unencapsulated variant of type 2 pneumococci were efficiently phagocytosed by both aerobically and anaerobically incubated human leukocytes. In the presence of O2, the pneumococci rapidly lost their viability, whereas during anaerobiosis,...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.47.1.277-281.1985
更新日期:1985-01-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章,多中心研究
doi:10.1128/IAI.66.1.356-360.1998
更新日期:1998-01-01 00:00:00
abstract::Whole blood and plasma from animals in the acute stage of leptospirosis contained a toxic factor which produced a cytopathic effect on fibroblastic L cell monolayers. Firm adsorption of cytotoxic factor (CTF) to L cells occurred within 1 h. The highest titer of CTF in plasma was reached at 24 h and declined after 48 h...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.8.3.401-405.1973
更新日期:1973-09-01 00:00:00
abstract::To evaluate the role of complement in pneumococcal and staphylococcal pneumonia, we decomplemented rats with cobra venom factor and inoculated them intratracheally with Staphylococcus aureus or type 25 pneumococci. S. aureus produced a patchy bronchopneumonia in normal Sprague-Dawley or Lewis rats, and decomplementati...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.37.3.1270-1277.1982
更新日期:1982-09-01 00:00:00
abstract::Athymic BALB/c nude mice and euthymic BALB/c mice were infected with Rickettsia akari by the intraperitoneal route. The rickettsialpox infection was terminated in euthymic mice with only two intraperitoneal injections of the antibiotic oxytetracycline, whereas prolonged treatment was necessary to terminate the infecti...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:
更新日期:1980-05-01 00:00:00
abstract::Bacteroides spp. may contribute to the chronicity of mixed infections by affecting the normal functions of polymorphonuclear leukocytes (PMN). This study evaluated the physiologic and biochemical responses of human peripheral blood PMN to a variety of strains of the oral periodontal pathogen Porphyromonas (Bacteroides...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.59.9.3134-3142.1991
更新日期:1991-09-01 00:00:00
abstract::Lower genital tract infection with Chlamydia trachomatis and C. muridarum can induce long-lasting hydrosalpinx in the upper genital tract of women and female mice, respectively. However, A/J mice were highly resistant to induction of long-lasting hydrosalpinx by C. muridarum. We further compared host inflammatory resp...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00055-14
更新日期:2014-07-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.66.12.5889-5896.1998
更新日期:1998-12-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.60.10.4301-4308.1992
更新日期:1992-10-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.63.7.2720-2728.1995
更新日期:1995-07-01 00:00:00
abstract::Establishment and maintenance of chronic lung infections with mucoid Pseudomonas aeruginosa in patients with cystic fibrosis (CF) require that the bacteria avoid host defenses. Elaboration of the extracellular, O-acetylated mucoid exopolysaccharide, or alginate, is a major microbial factor in resistance to immune effe...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.3.1895-1901.2001
更新日期:2001-03-01 00:00:00
abstract::Virulence of the fungal pathogen Aspergillus fumigatus is in part based on the saprophytic lifestyle that this mold has evolved. A crucial function for saprophytism resides in secreted proteases that allow assimilation of proteinaceous substrates. The impact of extracellular proteolytic activities on the pathogenesis ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00425-09
更新日期:2009-09-01 00:00:00
abstract::Lipopolysaccharide (LPS) from three human and four monkey isolates of Campylobacter jejuni was extracted in high yields that revealed ladder-like structures in polyacrylamide gels by direct silver staining. These observations demonstrate that C. jejuni possesses LPS with O-chain repeating units typical of the family E...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.12.5384-5387.1993
更新日期:1993-12-01 00:00:00
abstract::Because of the association of the group A streptococcal pyrogenic exotoxins (SPEs) with erythrogenic toxin used in the classical Dick test, the involvement of the SPEs in production of erythematous skin reactions was assessed. Unless they had been presensitized, young adult rabbits failed to show skin reactions after ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.26.2.467-472.1979
更新日期:1979-11-01 00:00:00
abstract::Apical membrane antigen 1 (AMA-1) is an invasion-related Plasmodium antigen that is expressed during both intracellular and extracellular asexual stages of the parasite's life cycle, making it an ideal target for induction of humoral and cellular immune responses that can protect against malaria. We show here that whe...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.05048-11
更新日期:2011-09-01 00:00:00