Dendritic cell targeting of<i>Bacillus anthracis</i>protective antigen expressed by<i>Lactobacillus acidophilus</i>protects mice from lethal challenge

Mohamadzadeh, Mansour; Duong, Tri; Sandwick, S. J.; Hoover, Timothy A.; Klaenhammer, Todd R.

doi:10.1073/pnas.0900029106

Cited by 186 publications

(162 citation statements)

References 51 publications

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“…subtilis phyA was codon optimized and cloned into pTRK882, under the control of the constitutive high-expressing P pgm promoter from L. acidophilus NCFM (37), in order to maximize expression in Lactobacillus species. This expression system has been previously demonstrated to be effective in enzyme expression (37), the production and delivery of immune modulating cytokines (59), and an anthrax vaccine (60), and its wide host range allowed the transformation of L. acidophilus, L. gallinarum, and L. gasseri. L. acidophilus NCFM and L. gasseri ATCC 33323 were originally isolated from the human gastrointestinal tract (61,62).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Phytate-Degrading Lactobacillus Culture Administration to Broiler Chickens

Askelson

Campasino

Lee

et al. 2014

Appl Environ Microbiol

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Probiotics have been demonstrated to promote growth, stimulate immune responses, and improve food safety of poultry. While widely used, their effectiveness is mixed, and the mechanisms through which they contribute to poultry production are not well understood. Microbial phytases are increasingly supplemented in feed to improve digestibility and reduce antinutritive effects of phytate. The microbial origin of these exogenous enzymes suggests a potentially important mechanism of probiotic functionality. We investigated phytate degradation as a novel probiotic mechanism using recombinant Lactobacillus cultures expressing Bacillus subtilis phytase. B. subtilis phyA was codon optimized for expression in Lactobacillus and cloned into the expression vector pTRK882. The resulting plasmid, pTD003, was transformed into Lactobacillus acidophilus, Lactobacillus gallinarum, and Lactobacillus gasseri. SDS-PAGE revealed a protein in the culture supernatants of Lactobacillus pTD003 transformants with a molecular weight similar to that of the B. subtilis phytase. Expression of B. subtilis phytase increased phytate degradation of L. acidophilus, L. gasseri, and L. gallinarum approximately 4-, 10-, and 18-fold over the background activity of empty-vector transformants, respectively. Phytase-expressing L. gallinarum and L. gasseri were administered to broiler chicks fed a phosphorusdeficient diet. Phytase-expressing L. gasseri improved weight gain of broiler chickens to a level comparable to that for chickens fed a control diet adequate in phosphorus, demonstrating proof of principle that administration of phytate-degrading probiotic cultures can improve performance of livestock animals. This will inform future studies investigating whether probiotic cultures are able to provide both the performance benefits of feed enzymes and the animal health and food safety benefits traditionally associated with probiotics. Lactobacillus species are important inhabitants of the gastrointestinal tracts of humans and animals and are increasingly being used as probiotic microorganisms due to their health-promoting properties (1, 2). Probiotics, sometimes called direct-fed microbials (DFM) when used in animals (3), are live microorganisms administered to confer a health benefit upon the host (4). Administration of probiotic Lactobacillus to poultry has been demonstrated to promote growth at levels similar to antibiotics (5, 6) and to reduce gastrointestinal colonization of human foodborne pathogens, including Campylobacter (7, 8), Clostridium (9), and Salmonella (10, 11). Because of concern over antibiotic-resistant pathogens and pressure from both consumers and regulatory agencies, probiotics have received increased interest as potential alternatives to antibiotic growth promoters (12). While probiotics are used widely in livestock production (13), their effectiveness is varied, and the mechanisms responsible for their benefits are not well understood.Phosphorus is an essential nutrient in poultry production (14), with dietary deficiencies leadin...

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Section: Discussionmentioning

confidence: 99%

Evaluation of Phytate-Degrading Lactobacillus Culture Administration to Broiler Chickens

Askelson

Campasino

Lee

et al. 2014

Appl Environ Microbiol

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“…86 Similar recombinant vaccine was developed using L. acidophilus engineered to express protective antigen (PA) of Bacillus anthracis to activate dendritic cell to protect host against anthrax. 87 Likewise, expression of PA in L. gasseri also provided 100% protection against anthrax in a mouse model. 88 Probiotics were also engineered to deliver vaccines to the mucosal surfaces.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 98%

Bioengineered probiotics, a strategic approach to control enteric infections

Amalaradjou

Bhunia

2013

Bioengineered

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“…Since Lactobacillus species thrive in the low pH of the stomach, using it as a vaccine delivery vehicle protects the vaccine subunit from the harsh acidic environment and protects the vaccine bioavailability. Meanwhile, researchers have also developed both inducible and constitutive expression vectors effective in lactobacilli species to deliver immunogenic antigens [1,[4][5][6]. Although immune tolerance to a commensal inhabitant of the gastrointestinal mucosa was an initial concern with this strategy certain lactobacilli such as L. gasseri, are able to overcome tolerance likely via strong innate adjuvant properties [7,8].…”

Section: Lactobacillus Species As An Antigen Delivery Vehiclementioning

confidence: 99%

“…With the goal to discover a specific DC-targeting peptide moiety, a phage display library was sequentially absorbed with monocytes, T cells, B cells, and Langerhans cells and then screened for the ability to bind human myeloid-derived DCs [11]. The obtained sequence was then tested for its in-vitro binding capacity and its application in antigen delivery in a murine model of oral vaccination by fusing this DC targeting peptide to PA of Bacillus anthracis [1,2,12].…”

Section: Targeting Dendritic Cells To Enhance the Immune Reactionmentioning

confidence: 99%

“…First, in order to protect the antigen from harsh gastric juices, Lactobacillus species, including L. acidophilus or L. gasseri, bacteria that can survive and thrive in the gastrointestinal tract, were modified to secrete the antigen of interest in the gut. Second, to assist in the delivery of antigen to the professional antigen presenting cells, a twelve amino-acid long tag was added to the immunogenic vaccine subunit [1,2].…”

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Directional Activation of Intestinal Dendritic Cells by Oral Targeted Multivalent Vaccine

Sahay¹

2012

J Vaccines Vaccin

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Dendritic cell targeting ofBacillus anthracisprotective antigen expressed byLactobacillus acidophilusprotects mice from lethal challenge

Abstract: anthrax ͉ lactic acid bacteria ͉ mucosal immunity ͉ oral ͉ vaccine

Cited by 186 publications

References 51 publications

Evaluation of Phytate-Degrading Lactobacillus Culture Administration to Broiler Chickens

Evaluation of Phytate-Degrading Lactobacillus Culture Administration to Broiler Chickens

Bioengineered probiotics, a strategic approach to control enteric infections

Directional Activation of Intestinal Dendritic Cells by Oral Targeted Multivalent Vaccine

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