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- Adenoviral Vector System: A Comprehensive Overview of Constructions, Therapeutic Applications and Host Responses.
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Anyeseu Park, Jeong Yoon Lee
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J. Microbiol. 2024;62(7):491-509. Published online July 22, 2024
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DOI: https://doi.org/10.1007/s12275-024-00159-4
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Abstract
- Adenoviral vectors are crucial for gene therapy and vaccine development, offering a platform for gene delivery into host cells. Since the discovery of adenoviruses, first-generation vectors with limited capacity have evolved to third-generation vectors flacking viral coding sequences, balancing safety and gene-carrying capacity. The applications of adenoviral vectors for gene therapy and anti-viral treatments have expanded through the use of in vitro ligation and homologous recombination, along with gene editing advancements such as CRISPR-Cas9. Current research aims to maintain the efficacy and safety of adenoviral vectors by addressing challenges such as pre-existing immunity against adenoviral vectors and developing new adenoviral vectors from rare adenovirus types and non-human species. In summary, adenoviral vectors have great potential in gene therapy and vaccine development. Through continuous research and technological advancements, these vectors are expected to lead to the development of safer and more effective treatments.
Journal Articles
- Vaccine Development for Severe Fever with Thrombocytopenia Syndrome Virus in Dogs.
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Seok-Chan Park, Da-Eun Jeong, Sun-Woo Han, Joon-Seok Chae, Joo-Yong Lee, Hyun-Sook Kim, Bumseok Kim, Jun-Gu Kang
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J. Microbiol. 2024;62(4):327-335. Published online April 18, 2024
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DOI: https://doi.org/10.1007/s12275-024-00119-y
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Abstract
- Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually known as the SFTS virus (SFTSV). Although the role of vertebrates in SFTSV transmission to humans remains uncertain, some reports have suggested that dogs could potentially transmit SFTSV to humans. Consequently, preventive measures against SFTSV in dogs are urgently needed. In the present study, dogs were immunized three times at two-week intervals with formaldehyde-inactivated SFTSV with two types of adjuvants. SFTSV (KCD46) was injected into all dogs two weeks after the final immunization. Control dogs showed viremia from 2 to 4 days post infection (dpi), and displayed white pulp atrophy in the spleen, along with a high level of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL) positive area. However, the inactivated SFTSV vaccine groups exhibited rare pathological changes and significantly reduced TUNEL positive areas in the spleen. Furthermore, SFTSV viral loads were not detected at any of the tested dpi. Our results indicate that both adjuvants can be safely used in combination with an inactivated SFTSV formulation to induce strong neutralizing antibodies. Inactivated SFTSV vaccines effectively prevent pathogenicity and viremia in dogs infected with SFTSV. In conclusion, our study highlighted the potential of inactivated SFTSV vaccination for SFTSV control in dogs.
- Lactobacillus acidophilus KBL409 Ameliorates Atopic Dermatitis in a Mouse Model
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Woon-ki Kim , You Jin Jang , SungJun Park , Sung-gyu Min , Heeun Kwon , Min Jung Jo , GwangPyo Ko
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J. Microbiol. 2024;62(2):91-99. Published online February 22, 2024
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DOI: https://doi.org/10.1007/s12275-024-00104-5
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Abstract
- Atopic dermatitis (AD) is a chronic inflammatory skin disease with repeated exacerbations of eczema and pruritus. Probiotics
can prevent or treat AD appropriately via modulation of immune responses and gut microbiota. In this study, we evaluated
effects of Lactobacillus acidophilus (L. acidophilus) KBL409 using a house dust mite (Dermatophagoides farinae)-induced
in vivo AD model. Oral administration of L. acidophilus KBL409 significantly reduced dermatitis scores and decreased
infiltration of immune cells in skin tissues. L. acidophilus KBL409 reduced in serum immunoglobulin E and mRNA levels
of T helper (Th)1 (Interferon-γ), Th2 (Interleukin [IL]-4, IL-5, IL-13, and IL-31), and Th17 (IL-17A) cytokines in skin tissues.
The anti-inflammatory cytokine IL-10 was increased and Foxp3 expression was up-regulated in AD-induced mice with
L. acidophilus KBL409. Furthermore, L. acidophilus KBL409 significantly modulated gut microbiota and concentrations
of short-chain fatty acids and amino acids, which could explain its effects on AD. Our results suggest that L. acidophilus
KBL409 is the potential probiotic for AD treatment by modulating of immune responses and gut microbiota of host.
- Environmental Adaptation of Psychrophilic Bacteria Subtercola spp. Isolated from Various Cryospheric Habitats
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Hanbyul Lee , Yong-Joon Cho , Ahnna Cho , Ok-Sun Kim
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J. Microbiol. 2023;61(7):663-672. Published online August 24, 2023
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DOI: https://doi.org/10.1007/s12275-023-00068-y
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Abstract
- Subtercola boreus K300T
is a novel psychrophilic strain that was isolated from permanently cold groundwater in Finland
and has also been found in several places in Antarctica including lake, soil, and rocks. We performed genomic and transcriptomic
analyses of 5 strains from Antarctica and a type strain to understand their adaptation to different environments.
Interestingly, the isolates from rocks showed a low growth rate and smaller genome size than strains from the other isolation
sources (lake, soil, and groundwater). Based on these habitat-dependent characteristics, the strains could be classified
into two ecotypes, which showed differences in energy production, signal transduction, and transcription in the clusters of
orthologous groups of proteins (COGs) functional category. In addition, expression pattern changes revealed differences
in metabolic processes, including uric acid metabolism, DNA repair, major facilitator superfamily (MFS) transporters, and
xylose degradation, depending on the nutritional status of their habitats. These findings provide crucial insights into the
environmental adaptation of bacteria, highlighting genetic diversity and regulatory mechanisms that enable them to thrive
in the cryosphere.
- Heterologous Production and Structure Determination of a New Lanthipeptide Sinosporapeptin Using a Cryptic Gene Cluster in an Actinobacterium Sinosporangium siamense
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Keita Saito , Keiichiro Mukai , Issara Kaweewan , Hiroyuki Nakagawa , Takeshi Hosaka , Shinya Kodani
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J. Microbiol. 2023;61(6):641-648. Published online June 12, 2023
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DOI: https://doi.org/10.1007/s12275-023-00059-z
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Abstract
- Lipolanthine is a subclass of lanthipeptide that has the modification of lipid moiety at the N-terminus. A cryptic biosynthetic
gene cluster comprising four genes (sinA, sinKC, sinD, and sinE) involved in the biosynthesis of lipolanthine was identified in
the genome of an actinobacterium Sinosporangium siamense. Heterologous coexpression of a precursor peptide coding gene
sinA and lanthipeptide synthetase coding gene sinKC in the host Escherichia coli strain BL21(DE3) resulted in the synthesis
of a new lanthipeptide, sinosporapeptin. It contained unusual amino acids, including one labionin and two dehydrobutyrine
residues, as determined using NMR and MS analyses. Another coexpression experiment with two additional genes of decarboxylase
(sinD) and N-acetyl transferase (sinE) resulted in the production of a lipolanthine-like modified sinosporapeptin.
- Identification and Characterization of HEPN‑MNT Type II TA System from Methanothermobacter thermautotrophicus ΔH
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Wonho Choi , Anoth Maharjan , Hae Gang Im , Ji-Young Park , Jong-Tae Park , Jung-Ho Park
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J. Microbiol. 2023;61(4):411-421. Published online April 18, 2023
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DOI: https://doi.org/10.1007/s12275-023-00041-9
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Abstract
- Toxin-antitoxin (TA) systems are widespread in bacteria and archaea plasmids and genomes to regulate DNA replication,
gene transcr!ption, or protein translation. Higher eukaryotic and prokaryotic nucleotide-binding (HEPN) and minimal
nucleotidyltransferase (MNT) domains are prevalent in prokaryotic genomes and constitute TA pairs. However, three gene
pairs (MTH304/305, 408/409, and 463/464) of Methanothermobacter thermautotropicus ΔH HEPN-MNT family have not
been studied as TA systems. Among these candidates, our study characterizes the MTH463/MTH464 TA system. MTH463
expression inhibited Escherichia coli growth, whereas MTH464 did not and blocked MTH463 instead. Using site-directed
MTH463 mutagenesis, we determined that amino acids R99G, H104A, and Y106A from the R[ɸX]4-6H motif are involved
with MTH463 cell toxicity. Furthermore, we established that purified MTH463 could degrade MS2 phage RNA, whereas
purified MTH464 neutralized MTH463 activity in vitro. Our results indicate that the endonuclease toxin MTH463 (encoding
a HEPN domain) and its cognate antitoxin MTH464 (encoding the MNT domain) may act as a type II TA system in
M. thermautotropicus ΔH. This study provides initial and essential information studying TA system functions, primarily
archaea HEPN-MNT family.
- Vibrio vulnificus PlpA facilitates necrotic host cell death induced by the pore forming MARTX toxin
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Changyi Cho , Sanghyeon Choi , Myung Hee Kim , Byoung Sik Kim
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J. Microbiol. 2022;60(2):224-233. Published online February 1, 2022
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DOI: https://doi.org/10.1007/s12275-022-1448-x
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7
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Abstract
- Opportunistic pathogen Vibrio vulnificus causes severe systemic
infection in humans with high mortality. Although multiple
exotoxins have been characterized in V. vulnificus, their
interactions and potential synergistic roles in pathogen-induced
host cell death have not been investigated previously.
By employing a series of multiple exotoxin deletion mutants,
we investigated whether specific exotoxins of the pathogen
functioned together to achieve severe and rapid necrotic cell
death. Human epithelial cells treated with V. vulnificus with
a plpA deletion background exhibited an unusually prolonged
cell blebbing, suggesting the importance of PlpA, a phospholipase
A2, in rapid necrotic cell death by this pathogen. Additional
deletion of the rtxA gene encoding the multifunctional
autoprocessing repeats-in-toxin (MARTX) toxin did not result
in necrotic cell blebs. However, if the rtxA gene was engineered
to produce an effector-free MARTX toxin, the cell
blebbing was observed, indicating that the pore forming activity
of the MARTX toxin is sufficient, but the MARTX toxin
effector domains are not necessary, for the blebbing. When
a recombinant PlpA was treated on the blebbed cells, the blebs
were completely disrupted. Consistent with this, MARTX
toxin-pendent rapid release of cytosolic lactate dehydrogenase
was significantly delayed in the plpA deletion background.
Mutations in other exotoxins such as elastase, cytolysin/hemolysin,
and/or extracellular metalloprotease did not affect
the bleb formation or disruption. Together, these findings indicate
that the pore forming MARTX toxin and the phospholipase
A2, PlpA, cooperate sequentially to achieve rapid necrotic
cell death by inducing cell blebbing and disrupting the
blebs, respectively.
- Vagococcus zengguangii sp. nov., isolated from yak faeces
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Yajun Ge , Dong Jin , Xin-He Lai , Jing Yang , Shan Lu , Ying Huang , Han Zheng , Xiaoyan Zhang , Jianguo Xu
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J. Microbiol. 2021;59(1):1-9. Published online December 23, 2020
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DOI: https://doi.org/10.1007/s12275-021-0406-3
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Abstract
- Two unknown Gram-stain-positive, catalase- and oxidasenegative,
non-motile, and coccus-shaped bacteria, designated
MN-17T and MN-09, were isolated from yaks faeces (Bos
grunniens) in the Qinghai-Tibet Plateau of China. 16S rRNA
gene sequence-based comparative analyses revealed that the
two strains were grouped within the genus Vagococcus, displaying
the highest similarity with Vagococcus xieshaowenii
CGMCC 1.16436T (98.6%) and Vagococcus elongatus CCUG
51432T (96.4%). Both strains grew optimally at 37°C and pH
7.0 in the presence of 0.5% (w/v) NaCl. The complete genome
of MN-17T comprises 2,085 putative genes with a total
of 2,190,262 bp and an average G + C content of 36.7 mol%.
The major fatty acids were C16:0 (31.2%), C14:0 (28.5%), and
C18:1ω9c (13.0%); the predominant respiratory quinone was
MK-7 (68.8%); the peptidoglycan type was A4α(L-Lys-DAsp);
and the major polar lipid was diphosphatidylglycerol.
Together, these supported the affiliation of strain MN-17T
to the genus Vagococcus. In silico DNA-DNA hybridization
and the average nucleotide identity values between MN-17T
and all recognized species in the genus were 21.6–26.1%
and 70.7–83.0%, respectively. MN-17T produced acid from
D-cellobiose, D-fructose, glycerol, D-glucose, N-acetyl-glucosamine,
gentiobiose, D-mannose, D-maltose, D-ribose, Dsaccharose,
salicin, D-trehalose, and D-xylose. These results
distinguished MN-17T and MN-09 from closely related species
in Vagococcus. Thus, we propose that strains MN-17T
and MN-09 represent a novel species in the genus Vagococcus,
with the name Vagococcus zengguangii sp. The type strain
is MN-17T (= CGMCC 1.16726T = GDMCC 1.1589T = JCM
33478T).
- Analyses of DNA double-strand break repair pathways in tandem arrays of HXT genes of Saccharomyces cerevisiae
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Ju-Hee Choi , Ye-Seul Lim , Min-Ku Kim , Sung-Ho Bae
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J. Microbiol. 2020;58(11):957-966. Published online October 30, 2020
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DOI: https://doi.org/10.1007/s12275-020-0461-1
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Abstract
- Eukaryotic genomes contain numerous homologous repeat
sequences including redundant genes with divergent homology
that can be potential recombination targets. Recombination
between divergent sequences is rare but poses a substantial
threat to genome stability. The hexose transporter
(HXT) gene family shares high sequence similarities at both
protein and DNA levels, and some members are placed close
together in tandem arrays. In this study, we show that spontaneous
interstitial deletions occur at significantly high rates
in HXT gene clusters, resulting in chimeric HXT sequences
that contain a single junction point. We also observed that
DNA double-strand breaks created between HXT genes produce
primarily interstitial deletions, whereas internal cleavage
of the HXT gene resulted in gene conversions as well as deletion
products. Interestingly, interstitial deletions were less constrained
by sequence divergence than gene conversion. Moreover,
recombination-defective mutations differentially affected
the survival frequency. Mutations that impair single-strand
annealing (SSA) pathway greatly reduced the survival frequency
by 10–1,000-fold, whereas disruption of Rad51-dependent
homologous recombination exhibited only modest reduction.
Our results indicate that recombination in the tandemly
repeated HXT genes occurs primarily via SSA pathway.
- Iron interferes with quorum sensing-mediated cooperation in Pseudomonas aeruginosa by affecting the expression of ppyR and mexT, in addition to rhlR
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Feng Sun , Na Li , Lijia Wang , Huajun Feng , Dongsheng Shen , Meizhen Wang
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J. Microbiol. 2020;58(11):938-944. Published online October 30, 2020
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DOI: https://doi.org/10.1007/s12275-020-0264-4
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Abstract
- The stabilization of quorum sensing (QS) is vital for bacterial
survival in various environments. Although the mechanisms
of QS stabilization in certain conditions have been well studied,
the impact of environmental factors has received much
less attention. In this study, we show that the supplementation
of 25 μM iron in competition experiments and 50 μM in
evolution experiments to casein growth cultures significantly
increased the possibility of population collapse by affecting
elastase production. However, the expression of lasI and lasR
remained constant regardless of iron concentration and hence
this effect was not through interference with the LasIR circuit,
which mainly regulates the secretion of elastase in Pseudomonas
aeruginosa. However, the expression of rhlR was significantly
inhibited by iron treatment, which could affect the
production of elastase. Further, based on both reverse transcription
quantitative polymerase chain reaction and gene
knock-out assays, we show that iron inhibits the transcription
of ppyR and enhances the expression of mexT, both of which
decrease elastase production and correspondingly interfere
with QS stabilization. Our findings show that environmental
factors can affect the genes of QS circuits, interfering with QS
stabilization. These findings are not only beneficial in understanding
the mechanistic effect of iron on QS stabilization,
but also demonstrate the complexity of QS stabilization by
linking non-QS-related genes with QS traits.
- Anti-inflammatory and anti-oxidative effect of Korean propolis on Helicobacter pylori-induced gastric damage in vitro
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Moon-Young Song , Da-Young Lee , Eun-Hee Kim
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J. Microbiol. 2020;58(10):878-885. Published online September 2, 2020
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DOI: https://doi.org/10.1007/s12275-020-0277-z
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Abstract
- Helicobacter pylori, present in the stomach lining, is a Gramnegative
bacterium that causes various gastrointestinal diseases,
including gastritis and peptic ulcers. Propolis is a natural
resinous substance collected from a variety of plants,
and contains several natural bioactive substances. The aim of
this study was to investigate the anti-inflammatory and antioxidative
effects of Korean propolis on H. pylori-induced damage
in the human adenocarcinoma gastric cell line. The propolis
used in this study was obtained from the Korea Beekeeping
Association in South Korea. The expression of pro-inflammatory
interleukins (ILs), such as IL-8, IL-12, IL-1β, tumor
necrosis factor alpha, cyclooxygenase-2, and inducible
nitric oxide synthase, which was increased after H. pylori infection,
significantly decreased in a dose-dependent manner
upon pretreatment with Korean propolis, because of the suppression
of mitogen-activated protein kinases and nuclear
factor κB pathway. The anti-oxidative activity of propolis was
assessed using the 2,2-diphenyl-1-picrylhydrazyl hydrate free
radical assay. Korean propolis showed significant anti-oxidative
effects via reactive oxygen species scavenging. In addition,
pretreatment with Korean propolis upregulated the
expression of anti-oxidant enzymes through Nrf2 signaling
activation. These findings indicate that the use of Korean propolis,
which has anti-inflammatory and anti-oxidative effects,
can be promising for the prevention of H. pylori-induced gastric
damage.
- Caspase-3 inhibitor inhibits enterovirus D68 production
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Wenbo Huo , Jinghua Yu , Chunyu Liu , Ting Wu , Yue Wang , Xiangling Meng , Fengmei Song , Shuxia Zhang , Ying Su , Yumeng Liu , Jinming Liu , Xiaoyan Yu , Shucheng Hua
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J. Microbiol. 2020;58(9):812-820. Published online September 1, 2020
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DOI: https://doi.org/10.1007/s12275-020-0241-y
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Abstract
- Enterovirus D68 (EVD68) is an emerging pathogen that recently
caused a large worldwide outbreak of severe respiratory
disease in children. However, the relationship between
EVD68 and host cells remains unclear. Caspases are involved
in cell death, immune response, and even viral production.
We found that caspase-3 was activated during EVD68 replication
to induce apoptosis. Caspase-3 inhibitor (Z-DEVDFMK)
inhibited viral production, protected host cells from
the cytopathic effects of EVD68 infection, and prevented
EVD68 from regulating the host cell cycle at G0/G1. Meanwhile,
caspase-3 activator (PAC-1) increased EVD68 production.
EVD68 infection therefore activates caspase-3 for virus
production. This knowledge provides a potential direction
for the prevention and treatment of disease related to EVD68.
- Simultaneous detection of Salmonella spp., Pseudomonas aeruginosa, Bacillus cereus, and Escherichia coli O157:H7 in environmental water using PMA combined with mPCR
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Guoyang Xie , Shuang Yu , Wen Li , Dan Mu , Zoraida P. Aguilar , Hengyi Xu
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J. Microbiol. 2020;58(8):668-674. Published online June 25, 2020
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DOI: https://doi.org/10.1007/s12275-020-0084-6
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Abstract
- A multiplex polymerase chain reaction (mPCR) with propidium
monoazide (PMA) and internal amplification control
(IAC) for the simultaneous detection of waterborne pathogens
Salmonella spp., Pseudomonas aeruginosa, Bacillus
cereus, and Escherichia coli O157:H7, was developed. This
PMA-IAC-mPCR assay used four new specific primers based
on the genes for invA, ecfX, cesB, and fliC, respectively. A
16S rRNA primer was chosen for IAC to eliminate false negative
results
. The photosensitive dye, propidium monoazide
(PMA) was used to exclude signals from dead bacteria that
could lead to false positive results. In pure culture, the limits
of detection (LOD) were 101 CFU/ml for P. aeruginosa, 102
CFU/ml for both Salmonella spp. and E. coli O157:H7, and
103 CFU/ml for B. cereus, respectively. In addition, with a
6–8 h enrichment of all four bacteria that were combined in
a mixture that was spiked in water sample matrix, the LOD
was 3 CFU/ml for Salmonella spp., 7 CFU/ml for E. coli
O157:H7, 10 CFU/ml for B. cereus and 2 CFU/ml for P.
aeruginosa. This PMA-IAC-mPCR assay holds potential for
application in the multiplex assay of waterborne pathogens.
- Endophytic bacterial and fungal microbiota in different cultivars of cassava (Manihot esculenta Crantz)
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Hong Li , Chengliang Yan , Yanqiong Tang , Xiang Ma , Yinhua Chen , Songbi Chen , Min Lin , Zhu Liu
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J. Microbiol. 2020;58(7):614-623. Published online May 18, 2020
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DOI: https://doi.org/10.1007/s12275-020-9565-x
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Abstract
- Endophytes colonize tissues of healthy host plants and play
a crucial role in plant growth and development. However,
little attention has been paid to the endophytes of tuber crops
such as cassava, which is used as a staple food by approximately
800 million people worldwide. This study aimed to
elucidate the diversity and composition of endophytic bacterial
and fungal communities in different cassava cultivars
using high-throughput sequencing. Although no significant
differences in richness or diversity were observed among the
different cassava cultivars, the community compositions were
diverse. Two cultivars (SC124 and SC205) tolerant to root rot
exhibited similar community compositions, while two other
cultivars (SC10 and SC5), which are moderately and highly
susceptible to root rot, respectively, harboured similar community
compositions. Proteobacteria, Firmicutes, and Ascomycota
dominated the endophyte assemblages, with Weissella,
Serratia, Lasiodiplodia, Fusarium, and Diaporthe being the
predominant genera. The differentially abundant taxonomic
clades between the tolerant and susceptible cultivars were
mainly rare taxa, such as Lachnoclostridium_5, Rhizobium,
Lampropedia, and Stenotrophomonas. These seemed to be key
genera that affected the susceptibility of cassava to root rot.
Moreover, the comparison of KEGG functional profiles revealed
that ‘Environmental adaptation’ category was significantly
enriched in the tolerant cultivars, while ‘Infectious
diseases: Parasitic’ category was significantly enriched in the
susceptible cultivars. The present findings open opportunities
for further studies on the roles of endophytes in the susceptibility
of plants to diseases.
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