Les Baillie - Academia.edu (original) (raw)
Papers by Les Baillie
Elsevier eBooks, 1999
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PubMed, Jul 1, 1986
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BMC Microbiology, Apr 6, 2006
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The global increase in antimicrobial resistance is placing increasing pressure on healthcare syst... more The global increase in antimicrobial resistance is placing increasing pressure on healthcare systems today. Historically, clay minerals have been used to treat intestinal ailments and mild skin conditions. More recently, research has demonstrated that specific clays may possess antimicrobial properties. With this in mind, we have focused on a new method to treat Clostridium difficile (C. difficile), the leading cause of infectious diarrhoea within hospitals, and Methicillin-resistant Staphylococcus aureus (MRSA), the number one cause of hospital skin infections worldwide. Using geochemical techniques, such as X-ray diffraction and Inductively-coupled plasma mass spectrometry, the physicochemistry of seven test clays was determined to assist in understanding the antimicrobial mechanism of the clay. To test the antimicrobial capability of the test clays, viability counts were used with hydrated clay minerals and both antibiotic-susceptible and antibiotic-resistant pathogenic bacteria to assess the feasibility of using clay minerals as therapeutic agents, ie. ‘nutraceuticals’. The ‘French green’ clay, composed of 91% quartz, demonstrated complete sterilisation of both bacteria following overnight incubation; supporting previous research with other pathogenic organisms. To establish the use of clays as geo-medical therapeutics, further pharmacotoxicology using in vitro human tissue models (i.e. gut and skin) will be employed to elucidate the mechanisms of clay bioreactivity. This study will help to further the understanding of antimicrobial clays, potentially leading to alternative therapies to decrease the current over prescription of antibiotics and the rising emergence of antimicrobial resistance.
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The FASEB Journal, Apr 1, 2007
The ability of the endospore-forming, gram-positive bacterium Bacillus anthracis to survive in ac... more The ability of the endospore-forming, gram-positive bacterium Bacillus anthracis to survive in activated macrophages is key to its germination and survival. In a previous publication, we discovered that exposure of primary murine macrophages to B. anthracis endospores upregulated NOS 2 concomitant with an .NO-dependent bactericidal response. Since NOS 2 also generates O(2).(-), experiments were designed to determine whether NOS 2 formed peroxynitrite (ONOO(-)) from the reaction of .NO with O(2).(-) and if so, was ONOO(-) microbicidal toward B. anthracis. Our findings suggest that ONOO(-) was formed upon macrophage infection by B. anthracis endospores; however, ONOO(-) does not appear to exhibit microbicidal activity toward this bacterium. In contrast, the exosporium of B. anthracis, which exhibits arginase activity, protected B. anthracis from macrophage-mediated killing by decreasing .NO levels in the macrophage. Thus, the ability of B. anthracis to subvert .NO production has important implications in the control of B. anthracis-induced infection.
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Anaerobe, Feb 1, 2020
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Letters in Applied Microbiology, Sep 1, 2005
Bacillus anthracis is a pathogen of animals which rarely infects humans. Its use as a bioweapon h... more Bacillus anthracis is a pathogen of animals which rarely infects humans. Its use as a bioweapon has stimulated efforts to develop genetic typing methods and therapeutics to respond to an attack. Of particular concern is the transfer of virulence genes from B. anthracis to other closely related strains of bacillus.
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Journal of Applied Microbiology, Jun 1, 1998
The expression of Bacillus anthracis protective antigen (PA) in B. subtilis from the pag gene in ... more The expression of Bacillus anthracis protective antigen (PA) in B. subtilis from the pag gene in pPA101-1 was explored in different genetic backgrounds in an attempt to identify opportunities to maximize expression. Introduction of AtxA, which positively regulates PA expression in B. anthracis did not improve expression levels in the protease-deficient strain WB600. Plasmid pPA101-1 was found to carry a deletion which created a new fusion point between vector and insert sequence, and which removed part of the AtxA binding site. The deletion may have occurred as a consequence of recombination between TCTAT sequences within both the vector and insert. Host mutations could influence expression; PA levels from pPA101-1 are threefold higher in a ccpA mutant than in an otherwise isogenic parent, and eightfold higher in an abrB mutant. These data demonstrate that the introduction of mutations affecting catabolite repression and growth phase regulation results in an increase in the yield of PA in this host-vector system. Combining these mutations with a multiply protease-negative background could potentially allow further improvements in PA yield.
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Current Opinion in Microbiology, Feb 1, 2001
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2022 Asia-Pacific Microwave Conference (APMC), Nov 29, 2022
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Frontiers for Young Minds, Jul 13, 2021
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Vaccine, Nov 1, 2007
Previously two capsule-specific monoclonal antibodies (4VA5 and 3VIE5) were identified as protect... more Previously two capsule-specific monoclonal antibodies (4VA5 and 3VIE5) were identified as protective against Burkholderia pseudomallei in passive transfer experiments. Panning these antibodies against evolutionary phage libraries identified reactive peptides capable of inhibiting its parent monoclonal from binding to B. pseudomallei. Mice immunized with peptide conjugated to thyroglobulin developed serum antibodies capable of recognizing the immunizing peptide of which a subset recognized exopolysaccharide in the context of whole B. pseudomallei cells. These serum antibodies recognized protease treated B. pseudomallei but not B. thailandensis suggesting that these peptides are mimotopes of the B. pseudomallei capsular exopolysaccharide. In a murine model of acute melioidosis, immunization with the mimotope of the 4VA5 binding site extended the mean time to death to 8.00 days over the 2.18 days afforded by immunization with thyroglobulin alone. This mimotope may be of use in developing an antibody response against B. pseudomallei exopolysaccharide.
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Fems Immunology and Medical Microbiology, Oct 1, 2004
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Analyst, 2007
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Journal of Applied Microbiology, Aug 1, 1999
Protective antigen (PA), the major protective component of the existing vaccine, is a potent immu... more Protective antigen (PA), the major protective component of the existing vaccine, is a potent immunogen. Protective antigen in alhydrogel induced a high serum IgG titre (&amp;gt; log10 4) in both the C57B16 and Balb/c mouse and the predominant subclass of antibody induced was IgG1, indicating that the response to PA was predominantly Th2 directed. When plasmid DNA encoding PA was used to immunize the Balb/c mouse, a low serum IgG titre was detected (&amp;lt;/=log10 1), which was slightly increased by boosting with plasmid DNA. However, when mice immunized with plasmid DNA were later boosted with rPA, a significant and rapid increase in titre (up to threefold) was observed. Priming mice with PA-encoding plasmid DNA may be a mechanism of enhancing and accelerating the immune response to PA.
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Letters in Applied Microbiology, 1998
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Journal of Clinical Pathology, May 1, 1993
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Journal of Clinical Pathology, Oct 1, 1990
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Journal of Hospital Infection, Feb 1, 1992
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Elsevier eBooks, 1999
Bookmarks Related papers MentionsView impact
PubMed, Jul 1, 1986
Bookmarks Related papers MentionsView impact
BMC Microbiology, Apr 6, 2006
Bookmarks Related papers MentionsView impact
The global increase in antimicrobial resistance is placing increasing pressure on healthcare syst... more The global increase in antimicrobial resistance is placing increasing pressure on healthcare systems today. Historically, clay minerals have been used to treat intestinal ailments and mild skin conditions. More recently, research has demonstrated that specific clays may possess antimicrobial properties. With this in mind, we have focused on a new method to treat Clostridium difficile (C. difficile), the leading cause of infectious diarrhoea within hospitals, and Methicillin-resistant Staphylococcus aureus (MRSA), the number one cause of hospital skin infections worldwide. Using geochemical techniques, such as X-ray diffraction and Inductively-coupled plasma mass spectrometry, the physicochemistry of seven test clays was determined to assist in understanding the antimicrobial mechanism of the clay. To test the antimicrobial capability of the test clays, viability counts were used with hydrated clay minerals and both antibiotic-susceptible and antibiotic-resistant pathogenic bacteria to assess the feasibility of using clay minerals as therapeutic agents, ie. ‘nutraceuticals’. The ‘French green’ clay, composed of 91% quartz, demonstrated complete sterilisation of both bacteria following overnight incubation; supporting previous research with other pathogenic organisms. To establish the use of clays as geo-medical therapeutics, further pharmacotoxicology using in vitro human tissue models (i.e. gut and skin) will be employed to elucidate the mechanisms of clay bioreactivity. This study will help to further the understanding of antimicrobial clays, potentially leading to alternative therapies to decrease the current over prescription of antibiotics and the rising emergence of antimicrobial resistance.
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
The FASEB Journal, Apr 1, 2007
The ability of the endospore-forming, gram-positive bacterium Bacillus anthracis to survive in ac... more The ability of the endospore-forming, gram-positive bacterium Bacillus anthracis to survive in activated macrophages is key to its germination and survival. In a previous publication, we discovered that exposure of primary murine macrophages to B. anthracis endospores upregulated NOS 2 concomitant with an .NO-dependent bactericidal response. Since NOS 2 also generates O(2).(-), experiments were designed to determine whether NOS 2 formed peroxynitrite (ONOO(-)) from the reaction of .NO with O(2).(-) and if so, was ONOO(-) microbicidal toward B. anthracis. Our findings suggest that ONOO(-) was formed upon macrophage infection by B. anthracis endospores; however, ONOO(-) does not appear to exhibit microbicidal activity toward this bacterium. In contrast, the exosporium of B. anthracis, which exhibits arginase activity, protected B. anthracis from macrophage-mediated killing by decreasing .NO levels in the macrophage. Thus, the ability of B. anthracis to subvert .NO production has important implications in the control of B. anthracis-induced infection.
Bookmarks Related papers MentionsView impact
Anaerobe, Feb 1, 2020
Bookmarks Related papers MentionsView impact
Letters in Applied Microbiology, Sep 1, 2005
Bacillus anthracis is a pathogen of animals which rarely infects humans. Its use as a bioweapon h... more Bacillus anthracis is a pathogen of animals which rarely infects humans. Its use as a bioweapon has stimulated efforts to develop genetic typing methods and therapeutics to respond to an attack. Of particular concern is the transfer of virulence genes from B. anthracis to other closely related strains of bacillus.
Bookmarks Related papers MentionsView impact
Journal of Applied Microbiology, Jun 1, 1998
The expression of Bacillus anthracis protective antigen (PA) in B. subtilis from the pag gene in ... more The expression of Bacillus anthracis protective antigen (PA) in B. subtilis from the pag gene in pPA101-1 was explored in different genetic backgrounds in an attempt to identify opportunities to maximize expression. Introduction of AtxA, which positively regulates PA expression in B. anthracis did not improve expression levels in the protease-deficient strain WB600. Plasmid pPA101-1 was found to carry a deletion which created a new fusion point between vector and insert sequence, and which removed part of the AtxA binding site. The deletion may have occurred as a consequence of recombination between TCTAT sequences within both the vector and insert. Host mutations could influence expression; PA levels from pPA101-1 are threefold higher in a ccpA mutant than in an otherwise isogenic parent, and eightfold higher in an abrB mutant. These data demonstrate that the introduction of mutations affecting catabolite repression and growth phase regulation results in an increase in the yield of PA in this host-vector system. Combining these mutations with a multiply protease-negative background could potentially allow further improvements in PA yield.
Bookmarks Related papers MentionsView impact
Current Opinion in Microbiology, Feb 1, 2001
Bookmarks Related papers MentionsView impact
2022 Asia-Pacific Microwave Conference (APMC), Nov 29, 2022
Bookmarks Related papers MentionsView impact
Frontiers for Young Minds, Jul 13, 2021
Bookmarks Related papers MentionsView impact
Vaccine, Nov 1, 2007
Previously two capsule-specific monoclonal antibodies (4VA5 and 3VIE5) were identified as protect... more Previously two capsule-specific monoclonal antibodies (4VA5 and 3VIE5) were identified as protective against Burkholderia pseudomallei in passive transfer experiments. Panning these antibodies against evolutionary phage libraries identified reactive peptides capable of inhibiting its parent monoclonal from binding to B. pseudomallei. Mice immunized with peptide conjugated to thyroglobulin developed serum antibodies capable of recognizing the immunizing peptide of which a subset recognized exopolysaccharide in the context of whole B. pseudomallei cells. These serum antibodies recognized protease treated B. pseudomallei but not B. thailandensis suggesting that these peptides are mimotopes of the B. pseudomallei capsular exopolysaccharide. In a murine model of acute melioidosis, immunization with the mimotope of the 4VA5 binding site extended the mean time to death to 8.00 days over the 2.18 days afforded by immunization with thyroglobulin alone. This mimotope may be of use in developing an antibody response against B. pseudomallei exopolysaccharide.
Bookmarks Related papers MentionsView impact
Fems Immunology and Medical Microbiology, Oct 1, 2004
Bookmarks Related papers MentionsView impact
Analyst, 2007
Bookmarks Related papers MentionsView impact
Journal of Applied Microbiology, Aug 1, 1999
Protective antigen (PA), the major protective component of the existing vaccine, is a potent immu... more Protective antigen (PA), the major protective component of the existing vaccine, is a potent immunogen. Protective antigen in alhydrogel induced a high serum IgG titre (&amp;gt; log10 4) in both the C57B16 and Balb/c mouse and the predominant subclass of antibody induced was IgG1, indicating that the response to PA was predominantly Th2 directed. When plasmid DNA encoding PA was used to immunize the Balb/c mouse, a low serum IgG titre was detected (&amp;lt;/=log10 1), which was slightly increased by boosting with plasmid DNA. However, when mice immunized with plasmid DNA were later boosted with rPA, a significant and rapid increase in titre (up to threefold) was observed. Priming mice with PA-encoding plasmid DNA may be a mechanism of enhancing and accelerating the immune response to PA.
Bookmarks Related papers MentionsView impact
Letters in Applied Microbiology, 1998
Bookmarks Related papers MentionsView impact
Journal of Clinical Pathology, May 1, 1993
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Journal of Clinical Pathology, Oct 1, 1990
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Journal of Hospital Infection, Feb 1, 1992
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