The Role of Oxygen and Its Derivatives in Microbial Pathogenesis and Host Defense

Beaman, L; Beaman, Blaine L.

doi:10.1146/annurev.mi.38.100184.000331

Cited by 181 publications

(100 citation statements)

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“…NO-and/or superoxide-independent anti-microbial mechanisms have already been reported for M. avium [29,36], Listeria monocytogenes [53,54], Legionella pneumophila [55,56], Trypanosoma cruzi [57], Anaplasma phagocytophilum [58] Brucella [59] and Chlamydia [60,61]. Furthermore, oxygen-independent anti-microbial mechanisms of phagocytic cells have been suspected for a long time [62] and NADPH oxidase-independent control of Brucella [59] and M. avium [35] has been reported. TNF has also been reported to be dispensable for the anti-microbial control of infection by A. phagocytophilum [58].…”

Section: Discussionmentioning

confidence: 99%

Engagement of Toll‐like receptor 2 in mouse macrophages infected with Mycobacterium avium induces non‐oxidative and TNF‐independent anti‐mycobacterial activity

et al. 2008

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Toll-like receptor (TLR) 2 plays an important role in the immune response to mycobacterial infections, being required for optimal immunity against certain virulent Mycobacterium avium strains. Here we analyzed the role of TLR2 in the intra-macrophagic growth of M. avium, using macrophages from TLR2-deficient mice. We found that the engagement of TLR2/TLR6 and/or TLR2/TLR1 receptors induced bacteriostasis of M. avium inside bone marrow-derived macrophages in a MyD88-dependent way. Additionally, lipoproteins from the cell envelope of M. avium with a molecular mass of 20-25 kDa triggered this TLR2 pathway, leading to a decrease in the growth of the mycobacteria. Although TLR2 engagement induced the production of TNF, this cytokine as well as nitric oxide and superoxide molecules were not necessary for TLR2-mediated bacteriostasis. Finally, TLR ligation did not induce the expression of the 47-kDa guanosine triphosphatase (LRG-47) but it promoted an increased maturation of the phagosome with regards to acquisition of LAMP1. Our data show that triggering TLR2 inhibited M. avium growth by an as-yetunknown mechanism that may involve increased phagosome maturation.Key words: Immunity Á Nitric oxide Á Phagocytes IntroductionMacrophages initiate the innate immune response by recognizing pathogens, phagocytosing them and producing inflammatory mediators. The initiation of an effective response requires the recognition of conserved molecular structures (pathogen associated molecular patterns) found in a large variety of microbes, and recognized by pattern recognition receptors (PRR) that are expressed on myeloid and other cells [1, 2]. The mammalian Tolllike receptors (TLR) are a structurally conserved family that shares homology to the Drosophila Toll system and represent one group of PRR that plays an important role in the recognition of infecting microbes [1][2][3]. Distinct TLR recognize a variety of chemically diverse agonists. These include lipopolysaccharide (LPS), peptidoglycan, viral coat proteins, lipoproteins, glycolipids, dsRNA and CpG DNA [4].TLR are comprised of two major domains: an extracellular leucine-rich repeats (LRR) domain and an intracellular Toll/IL-1 receptor (TIR) domain. The TIR domain, which is present in all TLR, is responsible for initiating a signaling cascade through interactions with TIR-domain-containing adaptors. Most TLR, including TLR2, recruit the MyD88 adaptor molecule, which leads to the activation of nuclear factor (NF)-jB and mitogen-activated protein (MAP) kinases, resulting in the induction of inflammatory cytokines [5,6]. MyD88-and TLR2-deficient mice have been shown to be more susceptible to several microbial infections, including Mycobacterium avium infections [7,8]. However, there are at least three other adaptor proteins, some of which can be used in a TLR-specific way. Thus, this indicates that the signaling pathways through individual TLR may differ from each other and thereby result in different biological responses [9][10][11]. TLR2 recognizes a wide variety of microbial c...

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Section: Discussionmentioning

confidence: 99%

Engagement of Toll‐like receptor 2 in mouse macrophages infected with Mycobacterium avium induces non‐oxidative and TNF‐independent anti‐mycobacterial activity

et al. 2008

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“…This is due to the capacity of strains with intact katG genes and catalase-peroxidase activity to withstand the reactive oxygen intermediates produced by the host in response to infection (Beaman & Beaman, 1984). Numerous reports attest to the variable nature of the katG locus.…”

Section: Pcr and Genotypingmentioning

confidence: 99%

Koch's Bacillus – a look at the first isolate of Mycobacterium tuberculosis from a modern perspective

et al. 2003

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Using molecular methods the authors have studied mycobacterial DNA taken from a 19th century victim of tuberculosis. This was the case from which Robert Koch first isolated and cultured the organism responsible for tuberculosis. The mycobacteria were preserved within five glass culture tubes as abundant bacterial colonies on slopes of a gelatinous culture medium of unknown composition. Originally presented by Koch to surgical laryngologist Walter Jobson Horne in London in 1901, the relic has, since 1983, been in the care of the Royal College of Surgeons of England. Light and electron microscopy established the presence of acid-fast mycobacteria but showed that morphological preservation was generally poor. Eleven different genomic loci were successfully amplified by PCR. This series of experiments confirmed that the organisms were indeed Mycobacterium tuberculosis and further showed that the original strain was in evolutionary terms similar to ‘modern’ isolates, having undergone the TB D1 deletion. Attempts to determine the genotypic group of the isolate were only partially successful, due in part to the degraded nature of the DNA and possibly also to a truncation in the katG gene, which formed part of the classification scheme. Spoligotyping resulted in amplification of DR spacers consistent with M. tuberculosis but with discrepancies between independent extracts, stressing the limitations of this typing method when applied to poorly preserved material.

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“…ROS are highly reactive and can damage proteins, lipids, RNA and DNA (27,133). The generation and accumulation of O 2 *, H 2 O 2 and hydroxyl radicals (16,30,133) that target DNA, cellular membranes, metalloproteases and transcription factors (69,86,87,123,195) can be lethal to the organism. In bacteria, DNA damage appears to be the most significant consequence of oxidative stress [reviewed in (133)].…”

Section: Gingivalismentioning

confidence: 99%

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

Sheets

Robles-Price²,

McKenzie³

et al. 2008

Front Biosci

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Porphyromonas gingivalis, a major periodontal pathogen, must acquire nutrients from host derived substrates, overcome oxidative stress and subvert the immune system. These activities can be coordinated via the gingipains which represent the most significant virulence factor produced by this organism. In the context of our contribution to this field, we will review the current understanding of gingipain biogenesis, glycosylation, and regulation, as well as discuss their role in oxidative stress resistance and apoptosis. We can postulate a model, in which gingipains may be part of the mechanism for P. gingivalis virulence. KeywordsPorphyromonas gingivalis; gingipains; apoptosis; caspase-independent apoptosis; oxidative stress; VimA; anoikis; N-cadherin; VE-cadherin; integrin β1; VimA; VimE; VimF; DNA repair; glycosylation; virulence; host cell survival; HRgpA; RgpB; Kgp; Review INTRODUCTIONP. gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiological agent of periodontal disease and is also linked to cardiovascular disease and other systemic diseases [reviewed in (43,103)]. The inflammatory nature of periodontal disease implies that innate host defense mechanisms play a vital role in limiting bacterial growth. During active infection including tissue invasion, toxic reactive oxygen metabolites (e.g. superoxides, hydrogen peroxide and hydroxyl radicals) are mostly generated by polymorphonuclear leukocytes and macrophages (27,29). In order to survive in the inflammatory environment of the periodontal pocket, the bacterium must not only obtain nutrients for growth, but also overcome oxidative stress and subvert the immune defense system. Coordinated regulation of these activities would be beneficial to the bacterium. While there is documented evidence of the response of P. gingivalis to environmental stimulus (56,117,126), one possible mechanism for coordination may occur via the gingipains produced by this bacterium. The presence of P. gingivalis in the periodontal pocket and the high levels of gingipain activity detected in gingival crevicular fluid could implicate a role for gingipains in the destruction of the highly vascular periodontal tissue. Protease-associated degradation of cell-cell adhesion proteins on epithelial and endothelial cells resulting in cell death will compromise tissue integrity and facilitate spreading of the bacterium. Furthermore, degradation of the immune response components will facilitate the survival of the organism. Together, these activities may also satisfy the nutritional requirements of the organism. Gingipain-dependent heme accumulation on the bacterium cell surface may also act as an "oxidative sink", thus, leading to protection against oxidative stress (191,193). We will discuss the role of the gingipains in the survival/pathogenicity of P. gingivalis and the unique vim (virulence modulating) locus that is involved in regulation of the gingipains. We will highlight some of our observations that are consistent with the hypothesis that the gingipain...

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The Role of Oxygen and Its Derivatives in Microbial Pathogenesis and Host Defense

Cited by 181 publications

References 0 publications

Engagement of Toll‐like receptor 2 in mouse macrophages infected with Mycobacterium avium induces non‐oxidative and TNF‐independent anti‐mycobacterial activity

Engagement of Toll‐like receptor 2 in mouse macrophages infected with Mycobacterium avium induces non‐oxidative and TNF‐independent anti‐mycobacterial activity

Koch's Bacillus – a look at the first isolate of Mycobacterium tuberculosis from a modern perspective

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

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