Publications (36)233.54 Total impact
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Article: Pathogenic mechanisms of enterococcal endocarditis
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ABSTRACT: Enterococci are gram-positive bacteria that are now established as major nosocomial pathogens and have become increasingly important in recent years due to the development and transmission of antibiotic resistance traits. These organisms commonly cause a variety of nosocomial infections, including surgical wound infections and urinary tract infections, as well as cardiovascular infections such as bacteremia and endocarditis. Infective endocarditis is a life-threatening microbial infection of the endothelial surface of the heart, which typically occurs on heart valve tissue. The enterococci are the third most common cause of infective endocarditis, and are becoming increasingly significant in this disease. In this review, we discuss the role of enterococci in infective endocarditis and focus on the current knowledge of enterococcal virulence mechanisms, with specific reference to this disease.Current Infectious Disease Reports 04/2012; 2(4):315-321. -
Article: Staphylococcal superantigens in colonization and disease.
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ABSTRACT: Superantigens (SAgs) are a family of potent immunostimulatory exotoxins known to be produced by only a few bacterial pathogens, including Staphylococcus aureus. More than 20 distinct SAgs have been characterized from different S. aureus strains and at least 80% of clinical strains harbor at least one SAg gene, although most strains encode many. SAgs have been classically associated with food poisoning and toxic shock syndrome (TSS), for which these toxins are the causative agent. TSS is a potentially fatal disease whereby SAg-mediated activation of T cells results in overproduction of cytokines and results in systemic inflammation and shock. Numerous studies have also shown a possible role for SAgs in other diseases such as Kawasaki disease (KD), atopic dermatitis (AD), and chronic rhinosinusitis (CRS). There is also now a rich understanding of the mechanisms of action of SAgs, as well as their structures and function. However, we have yet to discover what purpose SAgs play in the life cycle of S. aureus, and why such a wide array of these toxins exists. This review will focus on recent developments within the SAg field in terms of the molecular biology of these toxins and their role in both colonization and disease.Frontiers in cellular and infection microbiology. 01/2012; 2:52. -
Article: CD1d-independent activation of mouse and human iNKT cells by bacterial superantigens.
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ABSTRACT: Invariant NKT (iNKT) cells are infrequent but important immunomodulatory lymphocytes that exhibit CD1d-restricted reactivity with glycolipid Ags. iNKT cells express a unique T-cell receptor (TCR) composed of an invariant α-chain, paired with a limited range of β-chains. Superantigens (SAgs) are microbial toxins defined by their ability to activate conventional T cells in a TCR β-chain variable domain (Vβ)-specific manner. However, whether iNKT cells are directly activated by bacterial SAgs remains an open question. Herein, we explored the responsiveness of mouse and human iNKT cells to a panel of staphylococcal and streptococcal SAgs and examined the contribution of major histocompatibility complex (MHC) class II and CD1d to these responses. Bacterial SAgs that target mouse Vβ8, such as staphylococcal enterotoxin B (SEB), were able to activate mouse hybridoma and primary hepatic iNKT cells in the presence of mouse APCs expressing human leukocyte antigen (HLA)-DR4. iNKT cell-mediated cytokine secretion in SEB-challenged HLA-DR4-transgenic mice was CD1d-independent and accompanied by a high interferon-γ:interleukin-4 ratio consistent with an in vivo Th1 bias. Furthermore, iNKT cells from SEB-injected HLA-DR4-transgenic mice, and iNKT cells from SEB-treated human PBMCs, showed early activation by intracellular cytokine staining and CD69 expression. Unlike iNKT cell stimulation by α-galactosylceramide, stimulation by SEB did not induce TCR downregulation of either mouse or human iNKT cells. We conclude that Vβ8-targeting bacterial SAgs can activate iNKT cells by utilizing a novel pathway that requires MHC class II interactions, but not CD1d. Therefore, iNKT cells fulfill important effector functions in response to bacterial SAgs and may provide attractive targets in the management of SAg-induced illnesses.Immunology and Cell Biology 11/2011; 90(7):699-709. · 3.66 Impact Factor -
Article: The T cell receptor beta-chain second complementarity determining region loop (CDR2beta governs T cell activation and Vbeta specificity by bacterial superantigens.
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ABSTRACT: Superantigens (SAgs) are microbial toxins defined by their ability to activate T lymphocytes in a T cell receptor (TCR) β-chain variable domain (Vβ)-specific manner. Although existing structural information indicates that diverse bacterial SAgs all uniformly engage the Vβ second complementarity determining region (CDR2β) loop, the molecular rules that dictate SAg-mediated T cell activation and Vβ specificity are not fully understood. Herein we report the crystal structure of human Vβ2.1 (hVβ2.1) in complex with the toxic shock syndrome toxin-1 (TSST-1) SAg, and mutagenesis of hVβ2.1 indicates that the non-canonical length of CDR2β is a critical determinant for recognition by TSST-1 as well as the distantly related SAg streptococcal pyrogenic exotoxin C. Frame work (FR) region 3 is uniquely critical for TSST-1 function explaining the fine Vβ-specificity exhibited by this SAg. Furthermore, domain swapping experiments with SAgs, which use distinct domains to engage both CDR2β and FR3/4β revealed that the CDR2β contacts dictate T lymphocyte Vβ-specificity. These findings demonstrate that the TCR CDR2β loop is the critical determinant for functional recognition and Vβ-specificity by diverse bacterial SAgs.Journal of Biological Chemistry 02/2011; 286(6):4871-81. · 4.77 Impact Factor -
Article: Lactobacillus reuteri-produced cyclic dipeptides quench agr-mediated expression of toxic shock syndrome toxin-1 in staphylococci.
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ABSTRACT: The production of the staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) by Staphylococcus aureus has been associated with essentially all cases of menstruation-associated toxic shock syndrome (TSS). In this work, we show that the human vaginal isolate Lactobacillus reuteri RC-14 produces small signaling molecules that are able to interfere with the staphylococcal quorum-sensing system agr, a key regulator of virulence genes, and repress the expression of TSST-1 in S. aureus MN8, a prototype of menstrual TSS S. aureus strains. Quantitative real-time PCR data showed that transcription from the Ptst promoter, as well as the P2 and P3 promoters of the agr system from all four agr subgroups of S. aureus, was strongly inhibited in response to growth with L. reuteri RC-14 cultural supernatant. Alterations in the transcriptional levels of two other virulence-associated regulators sarA and saeRS were also observed, indicating a potential overall influence of L. reuteri RC-14 signals on the production of virulence factors in S. aureus. S. aureus promoter-lux reporter strains were used to screen biochemically fractionated L. reuteri RC-14 supernatant, and the cyclic dipeptides cyclo(L-Phe-L-Pro) and cyclo(L-Tyr-L-Pro) were identified as the signaling molecules. The results from this work contribute to a better understanding of interspecies cell-to-cell communication between Lactobacillus and Staphylococcus, and provide a unique mechanism by which endogenous or probiotic strains may attenuate virulence factor production by bacterial pathogens.Proceedings of the National Academy of Sciences 01/2011; 108(8):3360-5. · 9.68 Impact Factor -
Article: Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome.
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ABSTRACT: Staphylococcal superantigens are pyrogenic exotoxins that cause massive T cell activation leading to toxic shock syndrome and death. Despite the strong adaptive immune response induced by these toxins, infections by superantigen-producing staphylococci are very common clinical events. We hypothesized that this may be partly a result of staphylococcal strains having developed strategies that downregulate the T cell response to these toxins. Here we show that the human interleukin-2 response to staphylococcal superantigens is inhibited by the simultaneous presence of bacteria. Such a downregulatory effect is the result of peptidoglycan-embedded molecules binding to Toll-like receptor 2 and inducing interleukin-10 production and apoptosis of antigen-presenting cells. We corroborated these findings in vivo by showing substantial prevention of mortality after simultaneous administration of staphylococcal enterotoxin B with either heat-killed staphylococci or Staphylococcus aureus peptidoglycan in mouse models of superantigen-induced toxic shock syndrome.Nature medicine 07/2009; 15(6):641-8. · 27.14 Impact Factor -
Article: Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome
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ABSTRACT: Staphylococcal superantigens are pyrogenic exotoxins that cause massive T cell activation leading to toxic shock syndrome and death. Despite the strong adaptive immune response induced by these toxins, infections by superantigen-producing staphylococci are very common clinical events. We hypothesized that this may be partly a result of staphylococcal strains having developed strategies that downregulate the T cell response to these toxins. Here we show that the human interleukin-2 response to staphylococcal superantigens is inhibited by the simultaneous presence of bacteria. Such a downregulatory effect is the result of peptidoglycan-embedded molecules binding to Toll-like receptor 2 and inducing interleukin-10 production and apoptosis of antigen-presenting cells. We corroborated these findings in vivo by showing substantial prevention of mortality after simultaneous administration of staphylococcal enterotoxin B with either heat-killed staphylococci or Staphylococcus aureus peptidoglycan in mouse models of superantigen-induced toxic shock syndrome.Nature Medicine 05/2009; 15(6):641-648. · 22.46 Impact Factor -
Article: Molecular requirements for MHC class II alpha-chain engagement and allelic discrimination by the bacterial superantigen streptococcal pyrogenic exotoxin C.
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ABSTRACT: Superantigens (SAgs) are microbial toxins that bind to both TCR beta-chain variable domains (Vbetas) and MHC class II molecules, resulting in the activation of T cells in a Vbeta-specific manner. It is now well established that different isoforms of MHC II molecules can play a significant role in the immune response to bacterial SAgs. In this work, using directed mutational studies in conjunction with functional analyses, we provide a complete functional map of the low-affinity MHC II alpha-chain binding interface of the SAg streptococcal pyrogenic exotoxin C (SpeC) and identify a functional epitope in the beta-barrel domain that is required for the activation of T cells. Using cell lines that exclusively express individual MHC II isoforms, our studies provide a molecular basis for the selectivity of SpeC-MHC II recognition, and provide one mechanism by how SAgs are capable of distinguishing between different MHC II alleles.The Journal of Immunology 10/2008; 181(5):3384-92. · 5.79 Impact Factor -
Article: Neutralization of multiple staphylococcal superantigens by a single-chain protein consisting of affinity-matured, variable domain repeats.
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ABSTRACT: Staphylococcus aureus secretes various toxins that act as superantigens by stimulating a large fraction of the host's T cells. Toxin binding to variable domains of T cell receptor beta chains (Vbeta) leads to massive release of inflammatory molecules and potentially to toxic shock syndrome (TSS). Previously, we generated soluble forms of different Vbeta domains with a high affinity for binding superantigens. However, a broader spectrum antagonist is required for the neutralization of multiple toxins. In the present study, we expressed Vbeta domains in tandem as a single-chain protein and neutralized the clinically important superantigens staphylococcal enterotoxin B and TSS toxin-1 with a single agent.The Journal of Infectious Diseases 08/2008; 198(3):344-8. · 6.41 Impact Factor -
Article: A novel loop domain in superantigens extends their T cell receptor recognition site.
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ABSTRACT: Superantigens (SAGs) interact with host immune receptors to induce a massive release of inflammatory cytokines that can lead to toxic shock syndrome and death. Bacterial SAGs can be classified into five distinct evolutionary groups. Group V SAGs are characterized by the alpha3-beta8 loop, a unique approximately 15 amino acid residue extension that is required for optimal T cell activation. Here, we report the X-ray crystal structures of the group V SAG staphylococcal enterotoxin K (SEK) alone and in complex with the TCR hVbeta5.1 domain. SEK adopts a unique TCR binding orientation relative to other SAG-TCR complexes, which results in the alpha3-beta8 loop contacting the apical loop of framework region 4, thereby extending the known TCR recognition site of SAGs. These interactions are absolutely required for TCR binding and T cell activation by SEK, and dictate the TCR Vbeta domain specificity of SEK and other group V SAGs.Journal of Molecular Biology 09/2007; 371(1):210-21. · 4.00 Impact Factor -
Article: Crystal structure of the streptococcal superantigen SpeI and functional role of a novel loop domain in T cell activation by group V superantigens.
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ABSTRACT: Superantigens (SAgs) are potent microbial toxins that bind simultaneously to T cell receptors (TCRs) and class II major histocompatibility complex molecules, resulting in the activation and expansion of large T cell subsets and the onset of numerous human diseases. Within the bacterial SAg family, streptococcal pyrogenic exotoxin I (SpeI) has been classified as belonging to the group V SAg subclass, which are characterized by a unique, relatively conserved approximately 15 amino acid extension (amino acid residues 154 to 170 in SpeI; herein referred to as the alpha3-beta8 loop), absent in SAg groups I through IV. Here, we report the crystal structure of SpeI at 1.56 A resolution. Although the alpha3-beta8 loop in SpeI is several residues shorter than that of another group V SAg, staphylococcal enterotoxin serotype I, the C-terminal portions of these loops, which are located adjacent to the putative TCR binding site, are structurally similar. Mutagenesis and subsequent functional analysis of SpeI indicates that TCR beta-chains are likely engaged in a similar general orientation as other characterized SAgs. We show, however, that the alpha3-beta8 loop length, and the presence of key glycine residues, are necessary for optimal activation of T cells. Based on Vbeta-skewing analysis of human T cells activated with SpeI and structural models, we propose that the alpha3-beta8 loop is positioned to form productive intermolecular contacts with the TCR beta-chain, likely in framework region 3, and that these contacts are required for optimal TCR recognition by SpeI, and likely all other group V SAgs.Journal of Molecular Biology 05/2007; 367(4):925-34. · 4.00 Impact Factor -
Article: Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1.
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ABSTRACT: Superantigens (SAGs) bind simultaneously to major histocompatibility complex (MHC) and T-cell receptor (TCR) molecules, resulting in the massive release of inflammatory cytokines that can lead to toxic shock syndrome (TSS) and death. A major causative agent of TSS is toxic shock syndrome toxin-1 (TSST-1), which is unique relative to other bacterial SAGs owing to its structural divergence and its stringent TCR specificity. Here, we report the crystal structure of TSST-1 in complex with an affinity-matured variant of its wild-type TCR ligand, human T-cell receptor beta chain variable domain 2.1. From this structure and a model of the wild-type complex, we show that TSST-1 engages TCR ligands in a markedly different way than do other SAGs. We provide a structural basis for the high TCR specificity of TSST-1 and present a model of the TSST-1-dependent MHC-SAG-TCR T-cell signaling complex that is structurally and energetically unique relative to those formed by other SAGs. Our data also suggest that protein plasticity plays an exceptionally significant role in this affinity maturation process that results in more than a 3000-fold increase in affinity.The EMBO Journal 03/2007; 26(4):1187-97. · 9.20 Impact Factor -
Article: T cell signalling induced by bacterial superantigens.
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ABSTRACT: Bacterial superantigens (SAgs) constitute a large family of bacterial toxins that share the capacity to induce massive activation of the human immune system. Such a feature is based on the ability of these toxins to activate T cells that express Beta-chains of the T cell antigen receptor (TCR) containing variable regions (V) coded by specific families of VBeta genes. In addition, bacterial SAgs bypass the need for processing by antigen-presenting cells by directly binding to major histocompatibility complex class II molecules on the surface of these cells. Emerging work indicates that bacterial SAgs utilize not only the canonical pathways of TCR-mediated T cell activation but also other pathways. Here, we review the structural information on recognition of bacterial SAgs by T cells, the TCR signalling induced by this recognition event, and the effector functions that this recognition triggers. We analyze experimental evidence suggesting the existence of alternative receptors and coreceptors for bacterial SAgs, and outline future challenges in the research with these toxins.Chemical immunology and allergy 02/2007; 93:161-80. -
Article: Molecular basis of TCR selectivity, cross-reactivity, and allelic discrimination by a bacterial superantigen: integrative functional and energetic mapping of the SpeC-Vbeta2.1 molecular interface.
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ABSTRACT: Superantigens activate large fractions of T cells through unconventional interactions with both TCR beta-chain V domains (Vbetas) and MHC class II molecules. The bacterial superantigen streptococcal pyrogenic exotoxin C (SpeC) primarily stimulates human Vbeta2(+) T cells. Herein, we have analyzed the SpeC-Vbeta2.1 interaction by mutating all SpeC residues that make contact with Vbeta2.1 and have determined the energetic and functional consequences of these mutations. Our comprehensive approach, including mutagenesis, functional readouts from both bulk T cell populations, and an engineered Vbeta2.1(+) Jurkat T cell, as well as surface plasmon resonance binding analysis, has defined the SpeC "functional epitope" for TCR engagement. Although only two SpeC residues (Tyr(15) and Arg(181)) are critical for activation of virtually all human CD3(+) T cells, a larger cluster of four hot spot residues are required for interaction with Vbeta2.1. Three of these residues (Tyr(15), Phe(75), and Arg(181)) concentrate their binding energy on the CDR2 loop residue Ser(52a), a noncanonical residue insertion found only in Vbeta2 and Vbeta4 chains. Plasticity of this loop is important for recognition by SpeC. Although SpeC interacts with the Vbeta2.1 hypervariable CDR3 loop, our data indicate these contacts have little to no influence on the functional interaction with Vbeta2.1. These studies also provide a molecular basis for selectivity and cross-reactivity of SpeC-TCR recognition and reveal a degree of fine specificity in these interactions, whereby certain SpeC mutants are capable of distinguishing between different alleles of the same Vbeta domain subfamily.The Journal of Immunology 01/2007; 177(12):8595-603. · 5.79 Impact Factor -
Article: Bacterial superantigens bypass Lck-dependent T cell receptor signaling by activating a Galpha11-dependent, PLC-beta-mediated pathway.
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ABSTRACT: The paradigm to explain antigen-dependent T cell receptor (TCR) signaling is based on the activation of the CD4 or CD8 coreceptor-associated kinase Lck. It is widely assumed that this paradigm is also applicable to signaling by bacterial superantigens. However, these bacterial toxins can activate human T cells lacking Lck, suggesting the existence of an additional pathway of TCR signaling. Here we showed that this alternative pathway operates in the absence of Lck-dependent tyrosine-phosphorylation events and was initiated by the TCR-dependent activation of raft-enriched heterotrimeric Galpha11 proteins. This event, in turn, activated a phospholipase C-beta and protein kinase C-mediated cascade that turned on the mitogen-activated protein kinases ERK-1 and ERK-2, triggered Ca(2+) influx, and translocated the transcription factors NF-AT and NF-kappaB to the nucleus, ultimately inducing the production of interleukin-2 in Lck-deficient T cells. The triggering of this alternative pathway by superantigens suggests that these toxins use a G protein-coupled receptor as a coreceptor on T cells.Immunity 08/2006; 25(1):67-78. · 21.64 Impact Factor -
Article: Long-range cooperative binding effects in a T cell receptor variable domain.
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ABSTRACT: Although cellular processes depend on protein-protein interactions, our understanding of molecular recognition between proteins remains far from comprehensive. Protein-protein interfaces are structural and energetic mosaics in which a subset of interfacial residues, called hot spots, contributes disproportionately to the affinity of the complex. These hot-spot residues can be further clustered into hot regions. It has been proposed that binding energetics between residues within a hot region are cooperative, whereas those between hot regions are strictly additive. If this idea held true for all protein-protein interactions, then energetically significant long-range conformational effects would be unlikely to occur. In the present study, we show cooperative binding energetics between distinct hot regions that are separated by >20 A. Using combinatorial mutagenesis and surface plasmon resonance binding analysis to dissect additivity and cooperativity in a complex formed between a variable domain of a T cell receptor and a bacterial superantigen, we find that combinations of mutations from each of two hot regions exhibited significant cooperative energetics. Their connecting sequence is composed primarily of a single beta-strand of the T cell receptor variable Ig domain, which has been observed to undergo a strand-switching event and does not form an integral part of the stabilizing core of this Ig domain. We propose that these cooperative effects are propagated through a dynamic structural network. Cooperativity between hot regions has significant implications for the prediction and inhibition of protein-protein interactions.Proceedings of the National Academy of Sciences 07/2006; 103(26):9867-72. · 9.68 Impact Factor -
Article: Inhibition of expression of a staphylococcal superantigen-like protein by a soluble factor from Lactobacillus reuteri.
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ABSTRACT: Lactobacillus reuteri RC-14 has previously been shown to inhibit Staphylococcus aureus infection in a rat surgical-implant model. To investigate the basis for this, communication events between the two bacterial species were examined. L. reuteri RC-14 and Staph. aureus Newman were grown in a co-culture apparatus that physically separates the two species, while allowing the passage of soluble compounds. Using two-dimensional gel electrophoresis (2D-E), protein expression changes in Staph. aureus were analysed in response to co-culture with medium alone, L. reuteri RC-14, and a Lactobacillus strain that did not inhibit Staph. aureus infection in the rat model. It was observed that one protein in particular, identified as staphylococcal superantigen-like protein 11 (SSL11), showed a dramatic decrease in expression in response to growth with L. reuteri RC-14. Genetic reporters that placed both gfp and lux under the transcriptional control of the SSL11 promoter confirmed the 2D-E results. Interestingly, using similar reporter gene experiments, it was observed that the Staph. aureus P3 promoter from the staphylococcal accessory gene regulator (agr) locus also showed a decrease in expression in response to growth in the presence of L. reuteri RC-14. It was further demonstrated that L. reuteri RC-14 supernatant contained small unidentified molecules that were able to repress the SSL11 and P3 promoters, but the repression of SSL11 occurred independently of the agr system. These results suggest that L. reuteri RC-14 has the potential to alter the virulence of Staph. aureus via secretion of cell-cell signalling molecules.Microbiology 05/2006; 152(Pt 4):1155-67. · 3.06 Impact Factor -
Article: An amino-terminal domain of Enterococcus faecalis aggregation substance is required for aggregation, bacterial internalization by epithelial cells and binding to lipoteichoic acid.
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ABSTRACT: Aggregation substance (AS), a plasmid-encoded surface protein of Enterococcus faecalis, plays important roles in virulence and antibiotic resistance transfer. Previous studies have suggested that AS-mediated aggregation of enterococcal cells could involve the binding of this protein to cell wall lipoteichoic acid (LTA). Here, a method to purify an undegraded form of Asc10, the AS of the plasmid pCF10, is described. Using this purified protein, direct binding of Asc10 to purified E. faecalis LTA was demonstrated. Equivalent binding of Asc10 to LTA purified from INY3000, an E. faecalis strain that is incapable of aggregation, was also observed. Surprisingly, mutations in a previously identified aggregation domain from amino acids 473 to 683 that abolished aggregation had no effect on LTA binding. In frame deletion analysis of Asc10 was used to identify a second aggregation domain located in the N-terminus of the protein from amino acids 156 to 358. A purified Asc10 mutant protein lacking this domain showed reduced LTA binding, while a purified N-terminal fragment from amino acids 44-331 had high LTA binding. Like the previously described aggregation domain, the newly identified Asc10((156-358)) aggregation domain was also required for efficient internalization of E. faecalis into HT-29 enterocytes. Thus, Asc10 possess two distinct domains required for aggregation and eukaryotic cell internalization: an N-terminal domain that promotes binding to LTA and a second domain located near the middle of the protein.Molecular Microbiology 06/2004; 52(4):1159-71. · 5.01 Impact Factor -
Article: Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS): a new proteomic urinary test for patients with urolithiasis.
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ABSTRACT: SELDI-TOF-MS is a highly sensitive protein-analysis tool capable of detecting minute protein profile differences between biological samples. As proteins have been associated with urinary tract calculi, protein-based urinalysis may offer insights into their diagnosis. The purpose of this study was to evaluate SELDI-TOF-MS as a potential method for identifying urinary biomarkers of urolithiasis. Midstream sterile urine samples were obtained from 25 male patients with a confirmed diagnosis of urolithiasis (test group) and 25 male subjects with no known history of the disease (controls). Urinary levels of oxalate, total protein, albumin, and osteopontin were determined. Protein profiles were generated using SELDI-TOF-MS.SELDI-TOF-MS profiling revealed a relationship between protein peak intensities at 67 and 24 kDa that differed between the two groups. The ratio of p67:p24 was found to be less than 1.0 in all of the control samples (mean 0.26), while 18 out of 25 (72%) of the test group samples displayed a ratio greater than 1.0 (total group mean 4.75, P<0.001). Albumin, total protein, and oxalate levels were higher in the test group than the controls. Although SELDI-TOF-MS is not yet in widespread use in hospital and diagnostic laboratories, this system represents a promising new method for rapidly identifying patients with urolithiasis.Journal of Clinical Laboratory Analysis 02/2004; 18(3):170-5. · 1.38 Impact Factor -
Article: Potential uses of probiotics in clinical practice.
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ABSTRACT: Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. There is now mounting evidence that selected probiotic strains can provide health benefits to their human hosts. Numerous clinical trials show that certain strains can improve the outcome of intestinal infections by reducing the duration of diarrhea. Further investigations have shown benefits in reducing the recurrence of urogenital infections in women, while promising studies in cancer and allergies require research into the mechanisms of activity for particular strains and better-designed trials. At present, only a small percentage of physicians either know of probiotics or understand their potential applicability to patient care. Thus, probiotics are not yet part of the clinical arsenal for prevention and treatment of disease or maintenance of health. The establishment of accepted standards and guidelines, proposed by the Food and Agriculture Organization of the United Nations and the World Health Organization, represents a key step in ensuring that reliable products with suitable, informative health claims become available. Based upon the evidence to date, future advances with single- and multiple-strain therapies are on the horizon for the management of a number of debilitating and even fatal conditions.Clinical Microbiology Reviews 11/2003; 16(4):658-72. · 16.13 Impact Factor
Top co-authors
Top Journals
Institutions
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2003–2012
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The University of Western Ontario
- Department of Microbiology and Immunology
London, Ontario, Canada
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2006–2007
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Boston Biomedical Research Institute
Boston, MA, USA
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2003–2006
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Lawson Health Research Institute
London, Ontario, Canada
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2001–2003
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University of Minnesota Twin Cities
- Department of Microbiology
Minneapolis, MN, USA
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2002
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University of Minnesota Medical Center, Fairview
Minneapolis, MN, USA -
University of Minnesota Duluth
- Medical School
Duluth, MN, USA
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