The Use of Proteomics to Study Infectious Diseases

List, Edward O.; Berryman, Darlene E.; Bower, B.; Sackmann-Sala, Lucila; Gosney, Elahu S.; Ding, James; Okada, Shintaro; Kopchick, John J.

doi:10.2174/187152608784139640

Cited by 29 publications

(19 citation statements)

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“…Proteome studies have contributed substantially to our understanding of parasite biology and host-parasite interactions [19]. Mass spectrometry (MS) methods have been used to enable large-scale identification of proteins at different stages of the malarial parasite life cycle [20,21].…”

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum proteome changes in response to doxycycline treatment

Briolant

Almeras

Belghazi³

et al. 2010

Malar J

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BackgroundThe emergence of Plasmodium falciparum resistance to most anti-malarial compounds has highlighted the urgency to develop new drugs and to clarify the mechanisms of anti-malarial drugs currently used. Among them, doxycycline is used alone for malaria chemoprophylaxis or in combination with quinine or artemisinin derivatives for malaria treatment. The molecular mechanisms of doxycycline action in P. falciparum have not yet been clearly defined, particularly at the protein level.MethodsA proteomic approach was used to analyse protein expression changes in the schizont stage of the malarial parasite P. falciparum following doxycycline treatment. A comparison of protein expression between treated and untreated protein samples was performed using two complementary proteomic approaches: two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and isobaric tagging reagents for relative and absolute quantification (iTRAQ).ResultsAfter doxycycline treatment, 32 and 40 P. falciparum proteins were found to have significantly deregulated expression levels by 2D-DIGE and iTRAQ methods, respectively. Although some of these proteins have been already described as being deregulated by other drug treatments, numerous changes in protein levels seem to be specific to doxycycline treatment, which could perturb apicoplast metabolism. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to confirm this hypothesis.ConclusionsIn this study, a specific response to doxycycline treatment was distinguished and seems to involve mitochondrion and apicoplast organelles. These data provide a starting point for the elucidation of drug targets and the discovery of mechanisms of resistance to anti-malarial compounds.

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Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum proteome changes in response to doxycycline treatment

Briolant

Almeras

Belghazi³

et al. 2010

Malar J

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“…The search for clinically and epidemiologically useful biomarkers in human proteomes has yielded some success before. 63 High concentrations of three soluble products of cellular receptors (CD27, CD40L, and CD120a/TNFR1) and plasma IL-6 in HIV-1 patients before combination therapy have been shown to predict AIDS-defining illnesses after treatment. 64 In patients with viral hepatitis, two commercially available serum marker panels (FibroSURE and FIBROSpect II) appear to be equally reliable in gauging the success of interferon-based therapy in patients with hepatic C virus infection.…”

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confidence: 99%

Identification of Three Immunologic Correlates for HIV Type 1 Pathogenesis in Youth

Song

Li²,

Wilson³

et al. 2011

AIDS Research and Human Retroviruses

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To evaluate the stability and heterogeneity of cytokine and chemokine profiles in 80 youth with and without HIV-1 infection, we tested plasma samples at repeated visits without antiretroviral therapy. Among nine analytes that were quantified using multiplexing assays, interleukin 10 (IL-10), IL-18, and soluble CD30 persistently showed a positive correlation with HIV-1 viral load (Spearman r ¼ 0.40-0.59, p < 0.01 for all). A negative correlation with CD4 þ T cell counts (r ¼ À0.40 to À0.60, p < 0.01 for all) was also persistent for the three analytes. Analyses restricted to 48 AIDS-free youth (96 visits) yielded similar findings, as did multivariable models in which race, sex, age, body mass index, and time interval between visits were treated as covariates. These relationships reflected two novel features observed for all three analytes. First, their presence in plasma was relatively stable between visits (r ¼ 0.50-0.90, p < 0.03), regardless of HIV-1 infection status. Second, pairwise correlation was strong and persistent in HIV-1-seropositive youth (r ¼ 0.40-0.59, p < 0.01), but not in HIV-1, seronegatives ( p > 0.13). Additional analytes, especially eotaxin/CCL11 and SDF-1b/CXCL12, had no correlation with HIV-1-related outcomes despite their stability between visits. Overall, circulating IL-10, IL-18, and soluble CD30 could partially track unfavorable responses to HIV-1 infection in youth. These markers of persistent immune activation are individually and collectively indicative of HIV-1 pathogenesis.

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“…Proteomics enables the qualitative and quantitative analyses of proteins in complex biological systems, such as cells, tissues, and body fluids under specific conditions or in response to different stimuli (Graham et al, 2011;Lim & Elenitoba-Johnson, 2004;List et al, 2008;Wu & Liu, 2009). Proteomics is an effective means to rapidly identify new proteins as diagnostic or prognostic markers and as therapeutic targets for various diseases including cancers, genetic diseases, and infectious diseases such as tuberculosis (Chung et al, 2007;Kavallaris & Marshall, 2005;Drake et al, 2005;Stulik & Butaye, 2011).…”

Section: Proteomics and Its Application In Tuberculosis Researchmentioning

confidence: 99%