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Article ; Online: GENETIC VARIATION OF LEPTOTROMBIDIUM (ACARI: TROMBICULIDAE) MITES CARRYING ORIENTIA TSUTSUGAMUSHI, THE BACTERIAL PATHOGEN CAUSING SCRUB TYPHUS.

Ogawa, Motohiko / Takada, Nobuhiro / Noda, Shinichi / Takahashi, Mamoru / Matsutani, Minenosuke / Kageyama, Daisuke / Ebihara, Hideki

The Journal of parasitology

2023 Volume 109, Issue 4, Page(s) 340–348

Abstract: Leptotrombidium (Acari: Trombiculidae) mites are carriers of Orientia tsutsugamushi, the bacterial pathogen causing scrub typhus in humans. Classification of Leptotrombidium is vital because limited mite species carry O. tsutsugamushi. Generally, ... ...

Abstract	Leptotrombidium (Acari: Trombiculidae) mites are carriers of Orientia tsutsugamushi, the bacterial pathogen causing scrub typhus in humans. Classification of Leptotrombidium is vital because limited mite species carry O. tsutsugamushi. Generally, Leptotrombidium at the larval stage (approximately 0.2 mm in size) are used for morphological identification. However, morphological identification is often challenging because it requires considerable skills and taxonomic expertise. In this study, we found that the full-length sequences of the mitochondrial cytochrome c oxidase subunit 1 gene varied among the significant Leptotrombidium. On the basis of these, we modified the canonical deoxyribonucleic acid (DNA) barcoding method for animals by redesigning the primer set to be suitable for Leptotrombidium. Polymerase chain reaction with the redesigned primer set drastically increased the detection sensitivity, especially against Leptotrombidium scutellare (approximately 17% increase), one of the significant mites carrying O. tsutsugamushi. Phylogenetic analysis showed that the samples morphologically classified as L. scutellare and Leptotrombidium pallidum were further split into 3 and 2 distinct subclusters respectively. The mean genetic distance (p-distance) between L. scutellare and L. pallidum was 0.2147, whereas the mean distances within each species were 0.052 and 0.044, respectively. Within L. scutellare, the mean genetic distances between the 3 subclusters were 0.1626-0.1732, whereas the distances within each subcluster were 0.003-0.017. Within L. pallidum, the mean genetic distance between the 2 subclusters was 0.1029, whereas the distances within each subcluster were 0.010-0.013. The DNA barcoding uncovered a broad genetic diversity of Leptotrombidium, especially of L. scutellare and L. pallidum, the notable species carrying O. tsutsugamushi. We conclude that the DNA barcoding using our primers enables precise and detailed classification of Leptotrombidium and implies the existence of a subgenotype in Leptotrombidium that had not been found by morphological identification.
MeSH term(s)	Animals ; Humans ; Scrub Typhus/microbiology ; Orientia tsutsugamushi/genetics ; Trombiculidae ; Phylogeny ; Acari ; Bacteria ; Genetic Variation
Language	English
Publishing date	2023-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	300870-8
ISSN	1937-2345 ; 0022-3395
ISSN (online)	1937-2345
ISSN	0022-3395
DOI	10.1645/22-97
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Article ; Online: Several catechins and flavonols from green tea inhibit severe fever with thrombocytopenia syndrome virus infection in vitro.

Ogawa, Motohiko / Shimojima, Masayuki / Saijo, Masayuki / Fukasawa, Masayoshi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

2020 Volume 27, Issue 1, Page(s) 32–39

Abstract: Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever caused by SFTS virus (SFTSV). The mortality rate of SFTS is pretty high, but no vaccines and antiviral drugs are currently available.: Methods! ...

Abstract	Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever caused by SFTS virus (SFTSV). The mortality rate of SFTS is pretty high, but no vaccines and antiviral drugs are currently available. Methods: The antiviral effects of six green tea-related polyphenols, including four catechins and two flavonols, on SFTSV were evaluated to identify natural antiviral compounds. Results: Pretreatment with all polyphenols inhibited SFTSV infection in a concentration-dependent manner. The half-maximal inhibitory concentrations of (-)-epigallocatechin gallate (EGCg) and (-)-epigallocatechin (EGC) were 1.7-1.9 and 11-39 μM, respectively. The selectivity indices of EGCg and EGC were larger than those of the other polyphenols. Furthermore, pretreatment with EGCg and EGC dose-dependently decreased viral attachment to the host cells. Additionally, the treatment of infected cells with EGCg and EGC inhibited infection more significantly at a lower multiplicity of infection (MOI) than at a higher MOI, and this effect was less effective than that of pretreatment. Pyrogallol, a trihydroxybenzene that is the structural backbone of both EGCg and EGC, also inhibited SFTSV infection, as did gallic acid. Conclusions: Our study revealed that green tea-related polyphenols, especially EGCg and EGC, are useful as candidate anti-SFTSV drugs. Furthermore, the structural basis of their antiviral activity was identified, which should enable investigations of more active drugs in the future.
MeSH term(s)	Catechin/pharmacology ; Flavonols ; Hemorrhagic Fevers, Viral ; Humans ; Severe Fever with Thrombocytopenia Syndrome ; Tea
Chemical Substances	Flavonols ; Tea ; Catechin (8R1V1STN48)
Language	English
Publishing date	2020-08-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1355399-9
ISSN	1437-7780 ; 1341-321X
ISSN (online)	1437-7780
ISSN	1341-321X
DOI	10.1016/j.jiac.2020.08.005
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Article ; Online: Evaluation of Recombinant Type-Specific Antigens of Orientia tsutsugamushi Expressed by a Baculovirus-Insect Cell System as Antigens for Indirect Immunofluorescence Assay in the Serological Diagnosis of Scrub Typhus.

Ogawa, Motohiko / Ando, Shuji / Saijo, Masayuki

Japanese journal of infectious diseases

2020 Volume 73, Issue 5, Page(s) 330–335

Abstract: Scrub typhus (ST) is a mite-borne rickettsiosis caused by the intracellular bacterium Orientia tsutsugamushi (OTS), which is classified as a biosafety level-3 (BSL-3) pathogen. For serological tests of ST, mouse fibroblast cells infected with the five ... ...

Abstract	Scrub typhus (ST) is a mite-borne rickettsiosis caused by the intracellular bacterium Orientia tsutsugamushi (OTS), which is classified as a biosafety level-3 (BSL-3) pathogen. For serological tests of ST, mouse fibroblast cells infected with the five prevalent serotypes of OTS in Japan are generally used as antigens for indirect immunofluorescence assay (IFA). In this study, Spodoptera frugiperda derived insect cell line (Sf9) cells infected with recombinant type-specific antigen (rTSA)-expressing baculovirus were used for IFA. The paired serum samples of 15 ST patients, 10 rickettsiosis patients, and 10 control individuals were used. IgM and IgG titers determined by the rTSA-based IFA were correlated with those determined by the OTS-infected cell-based IFA (R
MeSH term(s)	Animals ; Antibodies, Bacterial/blood ; Antigens, Bacterial/blood ; Baculoviridae/metabolism ; Fluorescent Antibody Technique, Indirect/methods ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Japan ; Mice ; Orientia tsutsugamushi/immunology ; Orientia tsutsugamushi/isolation & purification ; Recombinant Proteins/immunology ; Scrub Typhus/blood ; Scrub Typhus/diagnosis ; Serogroup ; Serologic Tests ; Sf9 Cells
Chemical Substances	Antibodies, Bacterial ; Antigens, Bacterial ; Immunoglobulin G ; Immunoglobulin M ; Recombinant Proteins
Language	English
Publishing date	2020-04-30
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1478383-6
ISSN	1884-2836 ; 1344-6304
ISSN (online)	1884-2836
ISSN	1344-6304
DOI	10.7883/yoken.JJID.2019.334
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Article ; Online: The combination of levodopa with levodopa-metabolizing enzyme inhibitors prevents severe fever with thrombocytopenia syndrome virus infection in vitro more effectively than single levodopa.

Ogawa, Motohiko / Murae, Mana / Mizukami, Tomoharu / Gemba, Ryutaro / Irie, Takuya / Shimojima, Masayuki / Ebihara, Hideki / Noguchi, Kohji / Fukasawa, Masayoshi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

2023 Volume 29, Issue 5, Page(s) 549–553

Abstract: Severe fever with thrombocytopenia syndrome is a hemorrhagic fever caused by a tick-borne infection. The causative agent, Dabie bandavirus, is also called the severe fever with thrombocytopenia syndrome virus (SFTSV). Ogawa et al. (2022) reported that ... ...

Abstract	Severe fever with thrombocytopenia syndrome is a hemorrhagic fever caused by a tick-borne infection. The causative agent, Dabie bandavirus, is also called the severe fever with thrombocytopenia syndrome virus (SFTSV). Ogawa et al. (2022) reported that levodopa, an antiparkinsonian drug with an o-dihydroxybenzene backbone, which is important for anti-SFTSV activity, inhibited SFTSV infection. Levodopa is metabolized by dopa decarboxylase (DDC) and catechol-O-methyltransferase (COMT) in vivo. We evaluated the anti-SFTSV efficacy of two DDC inhibitors, benserazide hydrochloride and carbidopa, and two COMT inhibitors, entacapone and nitecapone, which also have an o-dihydroxybenzene backbone. Only DDC inhibitors inhibited SFTSV infection with pretreatment of the virus (half-maximal inhibitory concentration [IC
MeSH term(s)	Humans ; Levodopa/pharmacology ; Levodopa/therapeutic use ; Carbidopa ; Catechol O-Methyltransferase/metabolism ; Severe Fever with Thrombocytopenia Syndrome/drug therapy ; Catechols/pharmacology ; Catechols/therapeutic use ; Enzyme Inhibitors/therapeutic use ; Phlebovirus
Chemical Substances	Levodopa (46627O600J) ; entacapone (4975G9NM6T) ; Carbidopa (MNX7R8C5VO) ; Catechol O-Methyltransferase (EC 2.1.1.6) ; Catechols ; Enzyme Inhibitors
Language	English
Publishing date	2023-03-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1355399-9
ISSN	1437-7780 ; 1341-321X
ISSN (online)	1437-7780
ISSN	1341-321X
DOI	10.1016/j.jiac.2023.02.017
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Article ; Online: Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies.

Inoue, Tetsuya / Yamamoto, Yuichiro / Sato, Kaoru / Okemoto-Nakamura, Yuko / Shimizu, Yoshimi / Ogawa, Motohiko / Onodera, Taishi / Takahashi, Yoshimasa / Wakita, Takaji / Kaneko, Mika K / Fukasawa, Masayoshi / Kato, Yukinari / Noguchi, Kohji

iScience

2024 Volume 27, Issue 4, Page(s) 109363

Abstract: A current challenge is the emergence of SARS-CoV-2 variants, such as BQ.1.1 and XBB.1.5, that can evade immune defenses, thereby limiting antibody drug effectiveness. Emergency-use antibody drugs, including the widely effective bebtelovimab, are losing ... ...

Abstract	A current challenge is the emergence of SARS-CoV-2 variants, such as BQ.1.1 and XBB.1.5, that can evade immune defenses, thereby limiting antibody drug effectiveness. Emergency-use antibody drugs, including the widely effective bebtelovimab, are losing their benefits. One potential approach to address this issue are bispecific antibodies which combine the targeting abilities of two antibodies with distinct epitopes. We engineered neutralizing bispecific antibodies in the IgG-scFv format from two initially non-neutralizing antibodies, CvMab-6 (which binds to the receptor-binding domain [RBD]) and CvMab-62 (targeting a spike protein S2 subunit epitope adjacent to the known anti-S2 antibody epitope). Furthermore, we created a bispecific antibody by incorporating the scFv of bebtelovimab with our anti-S2 antibody, demonstrating significant restoration of effectiveness against bebtelovimab-resistant BQ.1.1 variants. This study highlights the potential of neutralizing bispecific antibodies, which combine existing less effective anti-RBD antibodies with anti-S2 antibodies, to revive the effectiveness of antibody therapeutics compromised by immune-evading variants.
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2024.109363
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Article ; Online: Evaluation of a broad-ranging and convenient enzyme-linked immunosorbent assay using the lysate of infected cells with five serotypes of Orientia tsutsugamushi, a causative agent of scrub typhus.

Ogawa, Motohiko / Satoh, Masaaki / Saijo, Masayuki / Ando, Shuji

BMC microbiology

2017 Volume 17, Issue 1, Page(s) 7

Abstract: Background: Scrub typhus is a mite-borne rickettsiosis caused by infection of Orientia tsutsugamushi, which is endemic to several Asia-Pacific Rim countries, including Japan. Although micro-indirect immunofluorescent assay (micro-IFA) is the standard ... ...

Abstract	Background: Scrub typhus is a mite-borne rickettsiosis caused by infection of Orientia tsutsugamushi, which is endemic to several Asia-Pacific Rim countries, including Japan. Although micro-indirect immunofluorescent assay (micro-IFA) is the standard method for the serological diagnosis of scrub typhus, enzyme-linked immunosorbent assay (ELISA) is considered to be more objective, by providing digitized results as opposed to being subject to the judgment of the evaluator as in micro-IFA. Therefore, the aim of this study was to develop a broad-ranging ELISA using the five major prevalent serotypes of O. tsutsugamushi in Japan as the antigens. Furthermore, in contrast to previous studies that used purified microorganisms via ultracentrifugation, we directly used the infected cells, and evaluated the diagnostic accuracy of this simplified method to that of micro-IFA. Results: Evaluation of paired patient sera against the five serotypes showed that the accuracy of ELISA relative to micro-IFA was 87.4 and 79.5% for immunoglobulin (Ig)M and IgG assays, respectively, at the optimized cut-off value. Further evaluation of patient sera against the expected serotype of the infecting strain showed that the accuracy of ELISA compared to micro-IFA increased to 100 and 97.4% in the IgM and IgG assays, respectively. This suggests that use of the five prevalent serotypes contributed to the increase of the accuracy of ELISA. When applying the criteria of serological diagnosis for paired sera samples to ELISA, all 19 patients were diagnosed as positive; a ≥4-fold elevation of the antibody titer was observed in 15 of 19 patients that were positive, and very high antibody titers were observed in both paired sera samples of the remaining four patients. In addition, all samples of healthy subjects and patients with other types of rickettsiosis were diagnosed as negative using these criteria. Conclusions: Our results suggest the excellent performance of the new broad-ranging and convenient ELISA, which appears to be applicable for the diagnosis of scrub typhus patients infected with the wide variety of prevalent strains in Japan. Furthermore, the ELISA is more objective than the micro-IFA, and can therefore provide more accurate diagnoses in Japan.
Language	English
Publishing date	2017-01-05
Publishing country	England
Document type	Journal Article
ISSN	1471-2180
ISSN (online)	1471-2180
DOI	10.1186/s12866-016-0910-5
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Article ; Online: L-DOPA, a treatment for Parkinson's disease, and its enantiomer D-DOPA inhibit severe fever with thrombocytopenia syndrome virus infection in vitro.

Ogawa, Motohiko / Murae, Mana / Gemba, Ryutaro / Irie, Takuya / Shimojima, Masayuki / Saijo, Masayuki / Noguchi, Kohji / Fukasawa, Masayoshi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

2021 Volume 28, Issue 3, Page(s) 373–376

Abstract: Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever. Patients mainly develop fever, thrombocytopenia, and leukopenia. A high case fatality rate of 16.2-47% has been reported. Vaccines and antivirals that are effective against SFTS ... ...

Abstract	Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever. Patients mainly develop fever, thrombocytopenia, and leukopenia. A high case fatality rate of 16.2-47% has been reported. Vaccines and antivirals that are effective against SFTS virus (SFTSV) are not yet available in clinical practice. We previously showed that o-dihydroxybenzene is the important chemical core structure for anti-SFTSV activity. In this study, we evaluated the anti-SFTSV efficacy of 3-Hydroxy-L-tyrosine (L-DOPA), a treatment for Parkinson's disease and its enantiomer, 3-hydroxy-D-tyrosine (D-DOPA), both of which have an o-dihydroxybenzene backbone. SFTSV was preincubated with L- or D-DOPA and then inhibition of viral infection as well as viral attachment to host cells were evaluated by viral quantification. Both L- and D-DOPA inhibited SFTSV infection in a dose-dependent manner, mainly by blocking viral attachment to host cells. The half-maximal inhibitory concentration (IC
MeSH term(s)	Bunyaviridae Infections ; Hemorrhagic Fevers, Viral ; Humans ; Levodopa/therapeutic use ; Parkinson Disease/drug therapy ; Phlebovirus ; Severe Fever with Thrombocytopenia Syndrome ; Thrombocytopenia/drug therapy
Chemical Substances	Levodopa (46627O600J)
Language	English
Publishing date	2021-11-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1355399-9
ISSN	1437-7780 ; 1341-321X
ISSN (online)	1437-7780
ISSN	1341-321X
DOI	10.1016/j.jiac.2021.11.005
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Article ; Online: Obligate intracellular bacteria diversity in unfed Leptotrombidium scutellare larvae highlights novel bacterial endosymbionts of mites.

Ogawa, Motohiko / Takahashi, Mamoru / Matsutani, Minenosuke / Takada, Nobuhiro / Noda, Shinichi / Saijo, Masayuki

Microbiology and immunology

2019 Volume 64, Issue 1, Page(s) 1–9

Abstract: It is well known that the mite Leptotrombidium scutellare carries the pathogen of scrub typhus, Orientia tsutsugamushi. However, our understanding of other bacterial endosymbionts of mites is limited. This study investigated the diversity of the obligate ...

Abstract	It is well known that the mite Leptotrombidium scutellare carries the pathogen of scrub typhus, Orientia tsutsugamushi. However, our understanding of other bacterial endosymbionts of mites is limited. This study investigated the diversity of the obligate intracellular bacteria carried by L. scutellare using 16S rRNA gene amplicon analysis with next-generation sequencing. The results showed that the detected bacteria were classified into the genera Rickettsia, Wolbachia, and Rickettsiella and an unknown genus of the order Rickettsiales. For further classification of the detected bacteria, a representative read that was most closely related to the assigned taxonomic classification was subjected to homology search and phylogenic analysis. The results showed that some bacteria of the genus Rickettsia were identical or very close to the human pathogens Rickettsia akari, Rickettsia aeschlimannii, Rickettsia felis, and Rickettsia australis. The genetic distance between the genus Wolbachia bacteria in the present study and in previous reports is highly indicative that the bacteria in the present study can be classified as a new taxon of Wolbachia. This study detected obligate intracellular bacteria from unfed mites; thus, the mites did not acquire bacteria from infected animals or any other infectious sources. Finally, the present study demonstrated that various and novel bacterial endosymbionts of mites, in addition to O. tsutsugamushi, might uniquely evolve with the host mites throughout overlapping generations of the mite life cycle. The roles of the bacteria in mites and their pathogenicity should be further examined in studies based on bacterial isolation.
MeSH term(s)	Animals ; Bacteria/classification ; Bacteria/genetics ; Bacteria/isolation & purification ; Bacterial Physiological Phenomena ; Biodiversity ; High-Throughput Nucleotide Sequencing ; Humans ; Larva/microbiology ; Life Cycle Stages ; Mites/microbiology ; Orientia tsutsugamushi ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rickettsia/classification ; Rickettsia/genetics ; Scrub Typhus/microbiology ; Sequence Analysis ; Symbiosis ; Trombiculidae/microbiology ; Wolbachia/classification
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2019-10-23
Publishing country	Australia
Document type	Journal Article
ZDB-ID	224792-6
ISSN	1348-0421 ; 0385-5600
ISSN (online)	1348-0421
ISSN	0385-5600
DOI	10.1111/1348-0421.12745
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Article ; Online: In vitro evaluation of minimum inhibitory concentration of several antibacterial agents against Rickettsia japonica using a plaque reduction assay system.

Satoh, Masaaki / Kato, Hirofumi / Takayama-Ito, Mutsuyo / Ogawa, Motohiko / Ando, Shuji / Saijo, Masayuki

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

2019 Volume 25, Issue 11, Page(s) 917–919

Abstract: The study was conducted to determine the minimum inhibitory concentrations (MICs) of several antibacterial agents against Rickettsia japonica, which causes Japanese spotted fever. A plaque reduction assay as an in vitro culture method was conducted to ... ...

Abstract	The study was conducted to determine the minimum inhibitory concentrations (MICs) of several antibacterial agents against Rickettsia japonica, which causes Japanese spotted fever. A plaque reduction assay as an in vitro culture method was conducted to determine the MICs of antibacterial agents (4 types of tetracyclines: tetracycline, doxycycline, minocycline, and tigecycline; 3 types of quinolones: ciprofloxacin, ofloxacin, and levofloxacin; and 2 types of macrolides: azithromycin and clarythromycin) against R. japonica. R. japonica was sensitive to the antibacterial agents tested with MICs similar to those against other spotted fever rickettsia determined in previously described plaque reduction assays.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Humans ; Microbial Sensitivity Tests/methods ; Rickettsia/drug effects ; Rickettsia Infections/drug therapy ; Rickettsia Infections/microbiology ; Spotted Fever Group Rickettsiosis/drug therapy ; Spotted Fever Group Rickettsiosis/microbiology
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2019-06-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1355399-9
ISSN	1437-7780 ; 1341-321X
ISSN (online)	1437-7780
ISSN	1341-321X
DOI	10.1016/j.jiac.2019.05.019
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Article ; Online: Nitric oxide enhanced the growth of an obligated intracellular bacterium Orientia tsutsugamushi in murine macrophages.

Ogawa, Motohiko / Satoh, Masaaki / Kataoka, Michiyo / Ando, Shuji / Saijo, Masayuki

Microbial pathogenesis

2017 Volume 107, Page(s) 335–340

Abstract: Orientia tsutsugamushi is the causative agent of scrub typhus. It is an obligate intracellular bacterium that grows only in eukaryotic cells. Macrophages play an important role in innate immunity by surveilling the human body for pathogens. In present ... ...

Abstract	Orientia tsutsugamushi is the causative agent of scrub typhus. It is an obligate intracellular bacterium that grows only in eukaryotic cells. Macrophages play an important role in innate immunity by surveilling the human body for pathogens. In present study, it was demonstrated that O. tsutsugamushi propagated well in LPS-activated RAW 264.7 macrophages, but not in non-activated macrophages. In LPS-activated macrophages, the expression of Nos2, which encodes the inducible nitric oxide (NO) synthase (iNOS), was highly upregulated compared to those in non-activated macrophages. Parallel to this upregulation, high NO production was observed in LPS-activated macrophages. Transmissible electron microscopy showed that O. tsutsugamushi replicated in the cytosol of macrophages. Thus, O. tsutsugamushi was thought to escape the phagosomes at an early stage of phagosome maturation to avoid the bactericidal effect of NO. Furthermore, O. tsutsugamushi growth was enhanced in NO donor-supplied RAW 264.7 macrophages, as well as in LPS-activated, but not in non-activated macrophages. Consequently, these results suggested that NO was rather essential for enhancing the replication of O. tsutsugamushi in RAW 264.7 macrophages, despite the typically detrimental effects of NO against intracellular pathogens. In the present study, NO was suggested to activate specific pathways to enhance the growth of O. tsutsugamushi.
Language	English
Publishing date	2017-06
Publishing country	England
Document type	Journal Article
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2017.04.012
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