Exploitation of the Endocytic Pathway by
            <i>Orientia tsutsugamushi</i>
            in Nonprofessional Phagocytes

Chu, Hyuk; Lee, Jun Young; Han, Seung Hoon; Kim, Se Yoon; Cho, Nam Hyuk; Kim, Ik Sang; Choi, Myung Sik

doi:10.1128/iai.01023-06

Cited by 11 publications

(13 citation statements)

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“…It is supposed that the bacterial 56-kDa type-specific antigen and surface antigen C (ScaC) are involved in cell invasion [9]. In nonprofessional phagocytes [27] and polymorphonuclear leukocytes [28] [29] and cytosolic bacteria [30,31] activate the type I IFN pathway. HK bacteria, which are degraded in phagolysosomes, were unable to modulate the type I IFN response and induce IFN-β release by macrophages as was previously reported for monocytes [13].…”

Section: Discussionmentioning

confidence: 99%

Orientia tsutsugamushi, the causative agent of scrub typhus, induces an inflammatory program in human macrophages

Tantibhedhyangkul

Amara

Textoris

et al. 2013

Microbial Pathogenesis

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Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, a bacterium that primarily infects endothelial cells both in vitro and in vivo. Evidence suggests that the interaction of O. tsutsugamushi with myeloid cells may play a pivotal role in O. tsutsugamushi infection. We demonstrated that O. tsutsugamushi replicated within human monocyte-derived macrophages. Bacteria stimulated the expression of a large number of genes, including type I interferon genes, interferon-stimulated genes, inflammation-associated genes and apoptosis-related genes, and the release of inflammatory cytokines such as Tumor Necrosis Factor and interleukin-1β. In addition, O. tsutsugamushi induced an M1-type genetic program in macrophages. O. tsutsugamushi viability was required for the type I interferon response and, to a lesser degree, for the inflammatory response. As interferon-γ is known to elicit M1 polarization, we assessed the effect of interferon-γ on the fate of O. tsutsugamushi in macrophages. Exogenous interferon-γ partially inhibited O. tsutsugamushi replication within macrophages. Our results suggest that the inflammatory response induced by O. tsutsugamushi may account for the local and systemic inflammation observed in scrub typhus.

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Section: Discussionmentioning

confidence: 99%

Orientia tsutsugamushi, the causative agent of scrub typhus, induces an inflammatory program in human macrophages

Tantibhedhyangkul

Amara

Textoris

et al. 2013

Microbial Pathogenesis

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“…Rickettsiaceae use a zipper-like mechanism for uptake into the target cell (Ihn et al, 2000;Lee et al, 2008;Cho et al, 2010a). Once inside the cell, they escape from membrane-enclosed vacuoles in the endolysosomal pathway and undergo growth and replication directly in the host cytosol (Chu et al, 2006). The bacteria are therefore directly exposed to autophagy machinery Ko et al, 2013) and cytosolic immune receptors such as Nod1 and Nod2 (Cho et al, 2010b), and this has likely put selective pressure on these organisms to minimise receptor activation and downstream effectors.…”

Section: Rickettsialesmentioning

confidence: 99%

Peptidoglycan in obligate intracellular bacteria

Otten

Brilli

Vollmer

et al. 2017

Molecular Microbiology

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SummaryPeptidoglycan is the predominant stress‐bearing structure in the cell envelope of most bacteria, and also a potent stimulator of the eukaryotic immune system. Obligate intracellular bacteria replicate exclusively within the interior of living cells, an osmotically protected niche. Under these conditions peptidoglycan is not necessarily needed to maintain the integrity of the bacterial cell. Moreover, the presence of peptidoglycan puts bacteria at risk of detection and destruction by host peptidoglycan recognition factors and downstream effectors. This has resulted in a selective pressure and opportunity to reduce the levels of peptidoglycan. In this review we have analysed the occurrence of genes involved in peptidoglycan metabolism across the major obligate intracellular bacterial species. From this comparative analysis, we have identified a group of predicted ‘peptidoglycan‐intermediate’ organisms that includes the Chlamydiae, Orientia tsutsugamushi, Wolbachia and Anaplasma marginale. This grouping is likely to reflect biological differences in their infection cycle compared with peptidoglycan‐negative obligate intracellular bacteria such as Ehrlichia and Anaplasma phagocytophilum, as well as obligate intracellular bacteria with classical peptidoglycan such as Coxiella, Buchnera and members of the Rickettsia genus. The signature gene set of the peptidoglycan‐intermediate group reveals insights into minimal enzymatic requirements for building a peptidoglycan‐like sacculus and/or division septum.

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“…Orientia tsutsugamushi was cryopreserved in MEM containing 20% FBS and 5% dimethyl sulphoxide (DMSO) and stored at -80 C until use. The infectivity titre of inocula was determined as described previously [19] with slight modification. Briefly, the inoculum was five-fold serially diluted and inoculated onto L929 cells grown in a 24-well plate.…”

Section: Preparation Of Orientia Tsutsugamushi Inoculamentioning

confidence: 99%

Intrinsic fluoroquinolone resistance in Orientia tsutsugamushi

Tantibhedhyangkul

Angelakis

Tongyoo

et al. 2010

International Journal of Antimicrobial Agents

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Scrub typhus is a public health concern for a population of over a billion humans, with an estimated incidence of one million cases/year in endemic areas. Although doxycycline remains the standard therapy, fluoroquinolones have been used successfully in a few patients. However, there is also clinical evidence that fluoroquinolones are ineffective in the treatment of scrub typhus. To clarify this matter, we determined the in vitro susceptibility of Orientia tsutsugamushi strain Kato to ciprofloxacin and sequenced the quinolone resistance-determining region (QRDR) of the gyrA gene, the target of fluoroquinolones, of 18 fresh isolates from Lao PDR.Orientia tsutsugamushi strain Kato was resistant to ciprofloxacin and ofloxacin in vitro (minimum inhibitory concentration = 8 g/mL). All sequences obtained, including those from the two available genomes of O. tsutsugamushi (strains Boryong and Ikeda), had a Ser83Leu mutation in their QRDR domain that is known to be associated with fluoroquinolone resistance. These findings re-emphasise the usefulness of in silico analysis for the prediction of antibiotic resistance and suggest that fluoroquinolones should not be used in the treatment of scrub typhus.

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Exploitation of the Endocytic Pathway by Orientia tsutsugamushi in Nonprofessional Phagocytes

Cited by 11 publications

References 0 publications

Orientia tsutsugamushi, the causative agent of scrub typhus, induces an inflammatory program in human macrophages

Orientia tsutsugamushi, the causative agent of scrub typhus, induces an inflammatory program in human macrophages

Peptidoglycan in obligate intracellular bacteria

Intrinsic fluoroquinolone resistance in Orientia tsutsugamushi

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