Intracellular replication is essential for the virulence of Salmonella typhimurium.

Leung, Ka Yin; Finlay, B. Brett

doi:10.1073/pnas.88.24.11470

Cited by 241 publications

(224 citation statements)

References 27 publications

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“…This late remodelling of peptidoglycan in intracellular bacteria could be explained by the fact that many intracellular bacteria have ceased growing at this post-infection time. Indeed, kinetic studies have shown that the highest increase in the number of intracellular viable S. typhimurium is detected from 4-5 h to 8-9 h post-infection (Leung and Finlay, 1991;Garcia-del Portillo et al, 1993) The new peaks identified in the HPLC analysis of peptidoglycan from intracellular bacteria, i.e. 5/5Ј and 6/6Ј, became major components ( Fig.…”

Section: Resultsmentioning

confidence: 98%

“…Development of the proliferative intracellular lifestyle of S. typhimurium implies a change in the state of growth of infecting bacteria: when infection is performed with resting cells, i.e. a static overnight culture, initiation of intracellular growth takes an additional 4-5 h (Leung and Finlay, 1991;Garcia-del Portillo et al, 1993). Therefore, structural variations of peptidoglycan could merely be a consequence of the initiation of bacterial growth.…”

Section: Resultsmentioning

confidence: 99%

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Peptidoglycan structure of Salmonella typhimurium growing within cultured mammalian cells

Zöllner

et al. 1997

Molecular Microbiology

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SummaryThe cell wall structure of Salmonella typhimurium has been studied for the first time during transit from freeliving to parasitic lifestyles. Peptidoglycan of S. typhimurium proliferating within human epithelial cells contains a high proportion of previously unidentified muropeptides (5-10-fold higher than in extracellular bacteria). Amino acid and mass-spectrometry analyses showed that these new components consist of

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Peptidoglycan structure of Salmonella typhimurium growing within cultured mammalian cells

Zöllner

et al. 1997

Molecular Microbiology

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“…After 2 h incubation at 25 uC in a 5 % (v/v) CO 2 atmosphere, the cells were washed twice using Hanks' balanced salt solution (HBSS) (Sigma) to remove unattached cells. Intracellular replication inside the phagocytes was assayed by the method of Leung & Finlay (1991) with the following modifications. Thirty minutes after infection, phagocytes were washed once with HBSS and then incubated for 1?5 h in 5 % fetal calf serum-supplemented fresh L-15 medium with 100 mg gentamicin ml 21 .…”

Section: Methodsmentioning

confidence: 99%

A major catalase (KatB) that is required for resistance to H2O2 and phagocyte-mediated killing in Edwardsiella tarda

2003

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Edwardsiella tarda causes haemorrhagic septicaemia in fish and gastro-and extra-intestinal infections in animals including humans. Resistance to phagocyte-mediated killing is one of the virulence factors of Ed. tarda. The authors' previous studies using TnphoA transposon mutagenesis indicated that katB mutants derived from the strain PPD130/91 are at least 1?6 log higher in LD 50 values than the wild-type strain. These findings suggest the involvement of catalase (KatB) in Ed. tarda pathogenesis. In this study, experiments were conducted to characterize the contribution of KatB to Ed. tarda infection. Zymographic analyses indicated that the 22 Ed. tarda strains examined expressed three different types of catalase-peroxidases (Kat1-3) based on their mobility in non-denaturing polyacrylamide gels. KatB (Kat1), the major catalase enzyme, was expressed in eight out of 22 Ed. tarda strains, and was commonly found in virulent strains except AL9379. AL9379 has a mutated katB, which has a base substitution and a deletion that translate into stop codons in the catalase gene. KatB produced by PPD130/91 was located in both periplasmic and cytoplasmic fractions and was constitutively expressed in various growth phases. Kinetics studies indicated that the catalase provided resistance to H 2 O 2 -and phagocyte-mediated killing. Infection kinetics studies of katB mutant 34 in gourami fish demonstrated its inability to survive and replicate in phagocyte-rich organs and this prevented the dissemination of infections when compared to the wild-type. Complementation of catalase mutants restored the production of catalase, and led to an increase in the resistance to H 2 O 2 -and phagocyte-mediated killing, and a decrease in LD 50 values. This study has identified and characterized a major catalase gene (katB) that is required for resistance to H 2 O 2 -and phagocyte-mediated killing in Ed. tarda. The results also suggest that catalase may play a role as a virulence factor in Ed. tarda pathogenesis.

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“…In infections with intracellular parasites, including Salmonella serovars, the interplay between the activity of IFN-c and iron homeostasis within macrophages is a central battlefield deciding about the course of the disease [12,13]. S. typhimurium is a facultative intracellular microbe able to invade macrophages and to exploit these cells for multiplication and systemic spreading [14,15]. Within phagocytes, however, S. typhimurium has limited access to mammalian iron resources.…”

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confidence: 99%

Interferon‐γ limits the availability of iron for intramacrophage Salmonella typhimurium

et al. 2008

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In stimulating effector functions of mononuclear phagocytes, IFN-c is of pivotal importance in host defense against intramacrophage pathogens including salmonellae. As the activity of IFN-c is modulated by iron and since a sufficient availability of iron is essential for the growth of pathogens, we investigated the regulatory effects of IFN-c on iron homeostasis and immune function in murine macrophages infected with Salmonella typhimurium. In Salmonella-infected phagocytes, IFN-c caused a significant reduction of iron uptake via transferrin receptor 1 and resulted in an increased iron efflux caused by an enhanced expression of the iron exporter ferroportin 1. Moreover, the expression of haem oxygenase 1 and of the siderophore-capturing antimicrobial peptide lipocalin 2 was markedly elevated following bacterial invasion, with IFN-c exerting a super-inducing effect. This observed regulatory impact of IFN-c reduced the intracellular iron pools within infected phagocytes, thus restricting the acquisition of iron by engulfed Salmonella typhimurium while concomitantly promoting NO and TNF-a production. Our data suggest that the modulation of crucial pathways of macrophage iron metabolism in response to IFN-c concordantly aims at withdrawing iron from intracellular Salmonella and at strengthening macrophage immune response functions. These regulations are thus consistent with the principles of nutritional immunity. IntroductionHost defense against intracellular microbes such as salmonellae or mycobacteria strongly depends on cell-mediated immunity, a major component of which is characterized by interactions between Th1 cells and macrophages [1]. By secreting Th1 cytokines, particularly IFN-c, antigen-specific Th1 cells activate a plethora of microbicidal mechanisms in infected macrophages. Specifically, in mononuclear phagocytes infected with Salmonella enterica serovar typhimurium (S. typhimurium), IFN-c promotes the internalization of bacteria and stimulates their elimination by various mechanisms including reactive oxygen and nitrogen species (ROS and RNS), generated via NADPH phagocyte oxidase and iNOS, respectively [2][3][4][5]. In Salmonella-infected mice, treatment with recombinant IFN-c increases host survival and decreases bacterial numbers in liver and spleen [6]. Conversely, neutralization of murine IFN-c functions with specific antibodies results in reduced host survival and increased bacterial counts [7]. Eur. J. Immunol. 2008. 38: 1923-1936 Immunity to infection In humans, the central importance of IFN-c for immune response against salmonellae is highlighted by the fact that patients with genetic defects in the IL-12-induced production of IFN-c or in the IFN-c receptor 1 selectively suffer from infections with salmonellae and otherwise weakly pathogenic mycobacteria since their phagocytes fail to eliminate these microbes [8,9]. Iron serves as an essential nutrient for nearly all pathogenic microorganisms, and the expression of iron acquisition systems by infectious agents is associated with their virule...

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Intracellular replication is essential for the virulence of Salmonella typhimurium.

Cited by 241 publications

References 27 publications

Peptidoglycan structure of Salmonella typhimurium growing within cultured mammalian cells

Peptidoglycan structure of Salmonella typhimurium growing within cultured mammalian cells

A major catalase (KatB) that is required for resistance to H2O2 and phagocyte-mediated killing in Edwardsiella tarda

Interferon‐γ limits the availability of iron for intramacrophage Salmonella typhimurium

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