Macrophage and Galleria mellonella infection models reflect the virulence of naturally occurring isolates of B. pseudomallei, B. thailandensis and B. oklahomensis.
BACKGROUND
Burkholderia pseudomallei is the causative agent of melioidosis, a tropical disease of humans with a variable and often fatal outcome. In murine models of infection, different strains exhibit varying degrees of virulence. In contrast, two related species, B. thailandensis and B. oklahomensis, are highly attenuated in mice. Our aim was to determine whether virulence in mice is reflected in macrophage or wax moth larvae (Galleria mellonella) infection models.


RESULTS
B. pseudomallei strains 576 and K96243, which have low median lethal dose (MLD) values in mice, were able to replicate and induce cellular damage in macrophages and caused rapid death of G. mellonella. In contrast, B. pseudomallei strain 708a, which is attenuated in mice, showed reduced replication in macrophages, negligible cellular damage and was avirulent in G. mellonella larvae. B. thailandensis isolates were less virulent than B. pseudomallei in all of the models tested. However, we did record strain dependent differences. B. oklahomensis isolates were the least virulent isolates. They showed minimal ability to replicate in macrophages, were unable to evoke actin-based motility or to form multinucleated giant cells and were markedly attenuated in G. mellonella compared to B. thailandensis.


CONCLUSIONS
We have shown that the alternative infection models tested here, namely macrophages and Galleria mellonella, are able to distinguish between strains of B. pseudomallei, B. thailandensis and B. oklahomensis and that these differences reflect the observed virulence in murine infection models. Our results indicate that B. oklahomensis is the least pathogenic of the species investigated. They also show a correlation between isolates of B. thailandensis associated with human infection and virulence in macrophage and Galleria infection models.
Biosciences, College of Life and Environmental Sciences, Geoffrey Pope Building, University of Exeter, Stocker Road, Exeter, Devon, EX4 4QD, UK.
Matthew E
ME
Wand
Claudia M
CM
Müller
Richard W
RW
Titball
Stephen L
SL
Michell
D000818:Animals; D019117:Burkholderia / Q000472:pathogenicity*; D019121:Burkholderia Infections / Q000382:microbiology*; D016957:Burkholderia pseudomallei / Q000472:pathogenicity*; D002460:Cell Line; D007814:Larva / Q000382:microbiology*; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D018613:Microscopy, Confocal; D009036:Moths / Q000382:microbiology*; D014774:Virulence
J Med Microbiol. 2002 Jul;51(7):539-553
12132769
BMC Microbiol. 2010 Jan 29;10:28
20109238
Am J Trop Med Hyg. 2000 Feb;62(2):232-9
10813478
Mol Microbiol. 2010 May;76(3):677-89
20345664
BMC Microbiol. 2006 May 26;6:46
16725056
Mol Microbiol. 2005 Apr;56(1):40-53
15773977
Biotechniques. 1994 May;16(5):800-2
8068328
Infect Immun. 2001 Jan;69(1):34-44
11119486
J Infect Dis. 1977 Jan;135(1):103-7
833442
Trans R Soc Trop Med Hyg. 2008 Dec;102 Suppl 1:S111-6
19121670
Infect Immun. 2008 Nov;76(11):5402-11
18779342
J Bacteriol. 2008 Apr;190(7):2306-13
18223084
Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14240-5
15377794
Arch Ophthalmol. 1980 Jul;98(7):1224-5
7396773
Microbios. 1998;96(384):71-93
10093229
Aust Vet J. 2000 Mar;78(3):193-5
10860161
Expert Rev Anti Infect Ther. 2006 Jun;4(3):445-55
16771621
Cell Microbiol. 2001 Jun;3(6):381-93
11422081
Infect Immun. 2006 Jul;74(7):4349-53
16790809
Acta Trop. 2000 Feb 5;74(2-3):153-8
10674644
J Clin Microbiol. 2005 Feb;43(2):970-2
15695721
Genome Biol. 2010;11(8):R89
20799932
PLoS Negl Trop Dis. 2009 Sep 22;3(9):e519
19771149
Genome Biol Evol. 2010 Jan 22;2:102-16
20333227
BMC Immunol. 2009 Apr 27;10:20
19397822
Plasmid. 2005 Nov;54(3):219-28
15925406
J Clin Microbiol. 2006 Dec;44(12):4601-4
17050819
BMC Genomics. 2005 Dec 07;6:174
16336651
J Bacteriol. 2006 Feb;188(4):1551-66
16452439
Int J Syst Evol Microbiol. 2006 Sep;56(Pt 9):2171-2176
16957116
Infect Immun. 2000 Sep;68(9):5377-84
10948167
Nat Rev Microbiol. 2006 Apr;4(4):272-82
16541135
Mol Microbiol. 2002 Nov;46(3):649-59
12410823
J Bacteriol. 2005 Nov;187(22):7857-62
16267310
Infect Immun. 1996 Mar;64(3):782-90
8641782
FEMS Microbiol Lett. 2005 Nov 15;252(2):327-35
16242861
FEMS Microbiol Lett. 2007 Dec;277(1):64-9
17986086
Int J Syst Bacteriol. 1998 Jan;48 Pt 1:317-20
9542103
Microb Pathog. 2004 May;36(5):287-92
15043863