Given the increasing commercial and clinical relevance of probiotic cultures, improving their stress tolerance profile and ability to overcome the physio-chemical defences of the host is an important biological goal. Pathogenic bacteria have evolved sophisticated strategies to overcome host defences, interact with the immune system and interfere with essential host systems. We coin the term ‘patho-biotechnology’ to describe the exploitation of these valuable traits in biotechnology and biomedicine. This approach shows promise for the design of more technologically robust and effective probiotic cultures with improved biotechnological and clinical applications as well as the development of novel vaccine and drug delivery platforms.
SleatorR. D., and HillC. (2002) Bacterial osmoadaptation: the role of osmolytes in bacterial stress and virulence. FEMS Microbiol. Rev., 26, 49–71.
2.
FosterJ. W., and SpectorM. P. (1995) How Salmonella survive against the odds. Annu. Rev. Microbiol., 49, 145–174.
3.
CooteJ. G. (2001) Environmental sensing mechanisms in Bordetella.Adv. Microbiol. Physiol., 44, 141–181.
4.
MurphyC., CarrollC., and JordanK. N. (2006) Environmental survival mechanisms of the foodborne pathogen. Campylobacter jejuni. J. Appl. Microbiol., 100, 623–632.
5.
SleatorR. D., and HillC. (2006) Pathobiotechnology; using bad bugs to do good things. Curr. Opin. Biotechnol., 17, 211–216.
6.
RolandK. L., TingeS. A., KilleenK. P., and KochiS. K. (2005) Recent advances in the development of live, attenuated bacterial vectors. Curr. Opin. Mol. Ther., 1, 62–72.
7.
ZhaoX., LiZ., GuB., and FrankelF. R. (2005) Pathogenicity and immunogenicity of a vaccine strain of Listeria monocytogenes that relies on a suicide plasmid to supply an essential gene product. Infect. Immunpl., 73, 5789–5798.
8.
LiZ., ZhaoX., HigginsD. E., and FrankelF. R. (2005) Conditional lethality yields a new vaccine strain of Listeria monocytogenes for the induction of cell-mediated immunity. Infect. Immunol., 73, 5065–5073.
9.
BrockstedtD. G., GiedlinM. A., LeongM. L., BahjatK. S., GaoY., LuckettW., LiuW., CookD. N., PortnoyD. A., and DubenskyT. W.Jr. (2004) Listeria-based cancer vaccines that segregate immunogenicity from toxicity. Proc. Natl. Acad. Sci. USA, 101, 13832–13837.
10.
DietrichG., ViretJ. F., and GentschevI. (2003) Haemolysin A and listeriolysin–two vaccine delivery tools for the induction of cell-mediated immunity. Int. J. Parasitol., 33, 495–505.
11.
SaitoG., AmidonG. L., and LeeK. D. (2003) Enhanced cytosolic delivery of plasmid DNA by a sulfhydryl-activatable listeriolysin O/protamine conjugate utilizing cellular reducing potential. Gene Ther., 10, 72–83.
12.
StierE. M., MandaiM., and LeeK. D. (2005) Differential cytosolic delivery and presentation of antigen by listeriolysin O-liposomes to macrophages and dendritic cells. Mol. Pharm., 2, 74–82.
13.
ShahidiF., and HanX. Q. (1993) Encapsulation of food ingredients. Crit. Rev. Food Sci. Nutr., 33, 501–547.
14.
MaaY. F., and PrestrelskiS. J. (2000) Biopharmaceutical powders: particle formation and formulation considerations. Curr. Pharm. Biotechnol., 1, 283–302.
15.
GahanC. G., and HillC. (2005) Gastrointestinal phase of Listeria monocytogenes infection. J. Appl. Microbiol., 98, 1345–1353.
16.
ZoetendalE. G., VaughanE. E., and de VosW. M. (2006) A microbial world within us. Mol. Microbiol., 59, 1639–1650.
17.
KuipersO. P.Genomics for food biotechnology: prospects of the use of high throughput technologies for the improvement of food microorganisms. Curr. Opin. Biotechnol., 10, 511–516.
ShanahanF. (2005) The host-microbe interface within the gut. Best Pract. Res. Clin. Gastroenterol., 16, 915–931.
20.
BackhedF., LeyR. E., SonnenburgJ. L., PetersonD. A., and GordonJ. I. (2005) Host-bacterial mutualism in the human intestine. Science, 307, 1915–1920.
21.
FullerR. (1989) Probiotics in man and animals. J. Appl. Bacteriol., 66, 365–378.
22.
RastallR. A. (2004) Bacteria in the gut: friends and foes and how to alter the balance. J. Nutr., 134, 2022S–2026S.
23.
AmitalH., GilburdB., and ShoenfeldY. (2003) Intelligent nutrition: health-promoting mechanisms of probiotics. Isr. Med. Assoc. J., 5, 812–813.
24.
O'HaraA. M., O'ReganP., FanningA., O'MahonyC., MacsharryJ., LyonsA., BienenstockJ., O'MahonyL., and ShanahanF. (2006) Functional modulation of human intestinal epithelial cell responses by Bifidobacterium infantis and Lactobacillus salivarius.Immunology, 118, 202–215.
25.
ChenC. C., and WalkerW. A. (2005) Probiotics role in clinical disease states. Adv. Pediatr., 52, 77–113.
26.
FedorakR. N., and ModsenK. L. (2004) Probiotics and prebiotics in gastrointestinal disorders. Curr. Opin. Gastroenterol., 20, 146–155.
27.
HuebnerE. S., and SurawiczC. M. (2006) Probiotics in the prevention and treatment of gastrointestinal infections. Gastroenterol. Clin. North Am., 35, 355–365.
28.
SheehanV., SleatorR. D., FitzgeraldG., and HillC. (2006) Heterologous expression of BetL, a betaine uptake system, enhances the stress tolerance of Lactobacillus salivarius UCC118. Appl. Environ. Microbiol., 72, 2170–2177.
29.
SeegersJ. F. (2002) Lactobacilli as live vaccine delivery vectors: progress and prospects. Trends Biotechnol., 20, 508–515.
30.
GuimarãesV. D., GabrielJ. E., LefèvreF., CabanesD., GrussA., CossartP., AzevedoV., and LangellaP. (2005) Internalin-expressing Lactococcus lactis is able to invade small intestine of guinea pigs and deliver DNA into mammalian epithelial cells. Microbes Infect., 7, 836–844.
31.
HamonM., BierneH., and CossartP. (2006) Listeria monocytogenes: a multifaceted model. Nat. Rev. Microbiol., 4, 423–434.
32.
GlaserP., FrangeulL., BuchrieserC., RusniokC., AmendA., BaqueroF., BercheP., BloeckerH., BrandtP., ChakrabortyT., CharbitA., ChetouaniF., CouveE., de DaruvarA., DehouxP., DomannE., Dominguez-BernalG., DuchaudE., DurantL., DussurgetO., EntianK. D., FsihiH., Garcia-Del PortilloF., GarridoP., GautierL., GoebelW., Gomez-LopezN., HainT., HaufJ., JacksonD., JonesL. M., KaerstU., KreftJ., KuhnM., KunstF., KurapkatG., MaduenoE., MaitournamA., Mata VicenteJ., NgE., NedjariH., NordsiekG., NovellaS., de PablosB., Pérez-DiazJ. C., PurcellR., RemmelB., RoseM., SchlueterT., SimoesN., TierrezA., Vázquez-BolandJ. A., VossH., WehlandJ., and CossartP. (2001) Comparative genomics of Listeria species. Science, 294, 849–852.
33.
HainT., SteinwegC., KuenneC. T., BillionA., GhaiR., ChatterjeeS. S., DomannE., KarstU., GoesmannA., BekelT., BartelsD., KaiserO., MeyerF., PulherA., WeisshaarB., WehlandJ., LiangC., DandekarT., LampidisR., KreftJ., GoebelW., and CharkrabortyT. (2006) Whole genome sequence of Listeria welshimeri reveals common reduction with Listeria innocua as compared to Listeria monocytogenes.J. Bacteriol., 188, 7405–7415.
34.
GrayM. J., FreitagN. E., and BoorK. J. (2006) How the bacterial pathogen Listeria monocytogenes mediates the switch from environmental Dr. Jekyll to pathogenic Mr. Hyde. Infect Immunol., 74, 2505–2512.
35.
LecuitM. (2005) Understanding how Listeria monocytogenes targets and crosses host barriers. Clin. Microbiol. Infect., 11, 430–436.
36.
SleatorR. D., GahanC. G. M., and HillC. (2003) A post-genomic appraisal of osmotolerance in Listeria monocytogenes.Appl. Environ. Microbiol., 69, 1–9.
37.
KrimskyS. (2005) From Asilomar to industrial biotechnology: risks, reductionism and regulation. Sci. Cult. (Lond)., 14, 309–323.
38.
SteidlerL., NeirynckS., HuyghebaertN., SnoeckV., VermeireA., GoddeerisB., CoxE., RemonJ. P., and RemautE. (2003) Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nat. Biotechnol., 27, 785–789.
39.
SzafranskiP., MelloC. M., SanoT., SmithC. L., KaplanD. L., and CantorC. R. (1997). A new approach for the containment of micro-organisms: dual control of streptavidin expression by antisense RNA and the T7 transcription system. Proc. Natl. Acad. Sci. USA, 94, 1059–1063.
40.
TorresB., JaeneckeS., TimmisK. N., GarciaJ. L., and DiazE. (2003) A dual lethal system to enhance containment of recombinant microorganisms. Microbiology, 149, 3595–35601.
41.
LojoM. M. (1995) Thymine auxotrophy is associated with increased UV sensitivity in Escherichia coli and Bacillus subtilis.Mutant Res., 347, 25–30.
42.
ShanahanS. (2004) Probiotics and the immune response: how much can we expect?J. Pediatr. Gastroenterol. Nutr., 39, S748–8749.
43.
O'SullivanG. C., KellyP., O'HalloranS., CollinsJ. K., DunneC., and ShanahanF. (2005) Probiotics: an emerging therapy. Curr. Pharm. Des., 11, 3–10.
44.
AmitalH., GilburdB., and ShoenfeldY. (2003) Intelligent nutrition: health-promoting mechanisms of probiotics. Isr. Med. Assoc. J., 5, 812–813.
45.
FedorakR. N., and ModsenK. L.Probiotics and prebiotics in gastrointestinal disorders. Curr. Opin. Gastroenterol., 20, 146–155.
46.
SpillerR. C. (2005) Potential future therapies for irritable bowel syndrome: will disease modifying therapy as opposed to symptomatic control become a reality?Gastroenterol. Clin. North Am., 34, 337–354.
47.
AslamS., and MusherD. M. (2006) An update on diagnosis, treatment, and prevention of Clostridium difficile-associated disease. Gastroenterol. Clin. North Am., 35, 315–335.
48.
AslamS., HamillR. J., and MusherD. M. (2005) Treatment of Clostridium difficile-associated disease: old therapies and new strategies. Lancet Infect. Dis., 5, 549–557.
49.
SleatorR. D., GahanC. G. M., AbeeT., and HillC. (1999) Identification and disruption of BetL, a secondary glycine betaine transport system linked to the salt tolerance of Listeria monocytogenes LO28. Appl. Environ. Microbiol., 65, 2078–2083.
50.
SleatorR. D., GahanC.G.M., O'DriscollB., and HillC. (2000) Analysis of the role of betL in contributing to the growth and survival of Listeria monocytogenes LO28. Int. J. Food Microbiol., 60, 261–268.
51.
SleatorR. D., WoodJ. M., and HillC. (2003) Transcriptional regulation and post-translational activity of the betaine transporter BetL in Listeria monocytogenes is controlled by environmental salinity. J. Bacteriol., 185, 7140–7144.
52.
SleatorR. D., GahanC. G. M., FrancisG., O'BeirneD., and HillC. (2003) Osmolyte uptake in Listeria monocytogenes affects growth and survival in foods and during infection of an animal model. J. Appl. Microbiol., 95, 839–846.
53.
SmiddyM., SleatorR. D., KellyA., and HillC. (2004) A role for the compatible solutes glycine betaine and L-carnitine in listerial barotolerance. Appl. Environ. Microbiol., 70, 7555–7557.
54.
SmiddyM., O'GormanL., SleatorR. D., HillC., and KellyA. (2000) Greater high-pressure resistance of bacteria in oysters than in broth. Innov. Food Sci. Emerg. Technol., 6, 83–90.
55.
Wemekamp-KamphuisH. H., WoutersJ. A., SleatorR. D., GahanC. G. M., HillC., and AbeeT. (2002) Multiple deletion of the osmolyte transporters BetL, Gbu and OpuC of Listeria monocytogenes affects virulence and growth at high osmolarity. Appl. Environ. Microbiol., 68, 4710–4716.
56.
Wemekamp-KamphuisH. H., SleatorR. D., WoutersJ. A., HillC., and AbeeT. (2004) Molecular and physiological analysis of the role of osmolyte transporters BetL, Gbu, and OpuC in growth of Listeria monocytogenes at low temperatures. Appl. Environ. Microbiol., 70, 2912–2918.
57.
SleatorR. D., GahanC. G. M., and HillC. (2001) Identification and disruption of the proBA locus in Listeria monocytogenes: role of proline biosynthesis in salt tolerance and murine infection. Appl. Environ. Microbiol., 67, 2571–2577.
58.
SleatorR. D., GahanC. G. M., and HillC. (2001) Mutations in the listerial proB gene leading to proline overproduction: effects on salt tolerance and murine infection. Appl. Environ. Microbiol., 67, 4560–4565.
59.
StackH., SleatorR. D., BowersM., HillC., and GahanC. G. M. (2005) HtrA; Stress induction and virulence potential in Listeria monocytogenes.Appl. Environ. Microbiol., 71, 4241–4247.
60.
SleatorR. D., WoutersJ., GahanC. G. M., AbeeT., and HillC. (2001) Analysis of the role of OpuC., an osmolyte transport system, in salt tolerance and virulence potential of Listeria monocytogenes.Appl. Environ. Microbiol., 67, 2692–2698.
61.
HillC., CotterP., SleatorR. D., and GahanC. G. M. (2002) Bacterial stress response in Listeria monocytogenes: jumping the hurdles imposed by minimal processing. Int. Dairy J., 12, 273–283.
62.
SleatorR. D., Wemekamp-KamphuisH. H., GahanC. G. M., HillC., and AbeeT. (2005) A PrfA-regulated bile exclusion system (bilE) is a novel virulence factor in Listeria monocytogenes.Mol. Microbiol., 55, 1183–1195.
63.
BegleyM., SleatorR. D., GahanC. G. M., and HillC. (2005) The contribution of three bile-associated loci (bsh, pva and btlB) to gastrointestinal persistence and bile tolerance of Listeria monocytogenes.Infect. Immunol., 73, 894–904.
64.
PortnoyD. A., and JonesS. (1994) The cell biology of Listeria monocytogenes infection (escape from a vacuole). Ann. N. Y. Acad. Sci., 730, 15–25.
65.
GaillardJ. L., BercheP., FrehelC., GouinE., and CossartP. (1991) Entry of L. monocytogenes into cells is mediated by internalin, a repeat protein reminiscent of surface antigens from Gram-positive cocci. Cell, 65, 1127–1141.
