Foci of Listeria monocytogenes persist in the bone marrow. Dis Model Mech 2:39-46

Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Disease Models and Mechanisms (Impact Factor: 4.97). 02/2009; 2(1-2):39-46. DOI: 10.1242/dmm.000836
Source: PubMed

ABSTRACT Murine listeriosis is one of the most comprehensive and well-studied models of infection, and Listeria monocytogenes has provided seminal information regarding bacterial pathogenesis. However, many aspects of the mouse model remain poorly understood, including carrier states and chronic colonization which represent important features of the spectrum of host-pathogen interaction. Bone marrow has recently been shown to harbor L. monocytogenes, which spreads from this location to the central nervous system. Bone could, therefore, be an important chronic reservoir, but this infection is difficult to study because it involves only a few bacteria and the extent of infection cannot be assessed until after the animal is sacrificed. We employed in vivo bioluminescence imaging to localize L. monocytogenes bone infections over time in live mice, revealing that the bacteria grow in discrete foci. These lesions can persist in many locations in the legs of mice and are not accompanied by a histological indication such as granuloma or a neutrophil infiltratate. We demonstrate that highly attenuated hly mutants, which have defective intracellular replication, are capable of prolonged focal infection of the bone marrow for periods of up to several weeks. These results support the recently proposed hypothesis that the bone marrow is a unique niche for L. monocytogenes.

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    • "For example, the now commercially available Listeria monocytogenes strain Xen32 was first used to demonstrate that the gallbladder is an important organ reservoir of listerial replication and pathogen shedding [1-3]. Since then the Xen32 listerial strain has been used in multiple studies as a tool to study Listeria directed immune mechanisms in knockout mice [4] and kinetics of L. monocytogenes dissemination to target organs of listeriosis such as the bone marrow [5]. More recently, the bioluminescent Xen32 strain has also been used to study transplacental transmission of L. monocytogenes in fetal listeriosis [6,7]. "
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    ABSTRACT: In vivo bioluminescence imaging (BLI) is a powerful method for the analysis of host-pathogen interactions in small animal models. The commercially available bioluminescent Listeria monocytogenes strain Xen32 is commonly used to analyse immune functions in knockout mice and pathomechanisms of listeriosis. To analyse and image listerial dissemination after oral infection we have generated a murinised Xen32 strain (Xen32-mur) which expresses a previously described mouse-adapted internalin A. This strain was used alongside the Xen32 wild type strain and the bioluminescent L. monocytogenes strains EGDe-lux and murinised EGDe-mur-lux to characterise bacterial dissemination in orally inoculated BALB/cJ mice. After four days of infection, Xen32 and Xen32-mur infected mice displayed consistently higher rates of bioluminescence compared to EGDe-lux and EGDe-mur-lux infected animals. However, surprisingly both Xen32 strains showed attenuated virulence in orally infected BALB/c mice that correlated with lower bacterial burden in internal organs at day 5 post infection, smaller losses in body weights and increased survival compared to EGDe-lux or EGDe-mur-lux inoculated animals. The Xen32 strain was made bioluminescent by integration of a lux-kan transposon cassette into the listerial flaA locus. We show here that this integration results in Xen32 in a flaA frameshift mutation which makes this strain flagella deficient. The bioluminescent L. monocytogenes strain Xen32 is deficient in flagella expression and highly attenuated in orally infected BALB/c mice. As this listerial strain has been used in many BLI studies of murine listeriosis, it is important that the scientific community is aware of its reduced virulence in vivo.
    Gut Pathogens 07/2013; 5(1):19. DOI:10.1186/1757-4749-5-19 · 2.28 Impact Factor
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    • "Work by Hardy et al. (2004, 2006) has shown that L. monocytogenes 10403S colonizes the mouse gall bladder, a location with the potential to serve as a reservoir for reactivation of illness. Listeria has also been reported in the bone marrow of infected mice and humans (de Bruijn et al., 1998; Hardy et al., 2009; Khan et al., 2001). It would thus appear that the number of body sites that have the potential to serve as foci for Listeria replication may be more diverse than originally appreciated. "
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    ABSTRACT: Cardiac infections caused by the foodborne bacterium Listeria monocytogenes represent a significant but poorly studied facet of disease. It is not known whether L. monocytogenes cardiac infections stem solely from host susceptibility, or whether bacterial isolates exist that exhibit a tropism for cardiac tissue. Here we examine the cardio-invasive capacity of a recent L. monocytogenes cardiac case strain (07PF0776) as well as nine additional outbreak and clinical isolates. Mice infected with the cardiac isolate 07PF0776 had 10-fold more bacteria recovered from heart tissue than those infected with L. monocytogenes strain 10403S, a well-characterized clinical isolate originally obtained from a human skin lesion. Additional L. monocytogenes isolates exhibited varied capacities to colonize the hearts of mice; however, those with the highest efficiency of mouse cardiac invasion also demonstrated the highest levels of bacterial invasion in cultured myoblast cells. Our findings strongly suggest that subpopulations of L. monocytogenes strains have acquired an enhanced ability to target and invade the myocardium.
    Journal of Medical Microbiology 03/2011; 60(Pt 4):423-34. DOI:10.1099/jmm.0.027185-0 · 2.25 Impact Factor
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    • "ood example of how the signal intensity depends not only on the amount of bacteria but also on their location . Listeria monocytogenes was also detected in the faecal pellets , in - dicating that faeces may represent a source for reinfection or new infections . More recently , BPI has been used to study bone marrow infection by L . monocytogenes ( Hardy et al . , 2009 ) . As previously observed , infection of mice by this bacterium was cleared during the first hours , followed by dynamic relapses in different locations , including the bones . This complex pattern of infection would have been very difficult to identify using conventional methods because of the variety of sites of infection , the fluct"
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    ABSTRACT: According to World Health Organization estimates, infectious organisms are responsible for approximately one in four deaths worldwide. Animal models play an essential role in the development of vaccines and therapeutic agents but large numbers of animals are required to obtain quantitative microbiological data by tissue sampling. Biophotonic imaging (BPI) is a highly sensitive, nontoxic technique based on the detection of visible light, produced by luciferase-catalysed reactions (bioluminescence) or by excitation of fluorescent molecules, using sensitive photon detectors. The development of bioluminescent/fluorescent microorganisms therefore allows the real-time noninvasive detection of microorganisms within intact living animals. Multiple imaging of the same animal throughout an experiment allows disease progression to be followed with extreme accuracy, reducing the number of animals required to yield statistically meaningful data. In the study of infectious disease, the use of BPI is becoming widespread due to the novel insights it can provide into established models, as well as the impact of the technique on two of the guiding principles of using animals in research, namely reduction and refinement. Here, we review the technology of BPI, from the instrumentation through to the generation of a photonic signal, and illustrate how the technique is shedding light on infection dynamics in vivo.
    FEMS microbiology reviews 09/2010; 35(2):360-94. DOI:10.1111/j.1574-6976.2010.00252.x · 13.24 Impact Factor
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