The emergence of carbapenem-resistant Pseudomonas aeruginosa, a multi-drug-resistant bacteria, is becoming a serious
public health concern. This bacterium infects immunocompromised patients and has a high fatality rate. Both naturally and
synthetically produced chalcones are known to have a wide array of biological activities. The antibacterial properties of
synthetically produced chalcone were studied against P. aeruginosa. In vitro, study of the compound (chalcone derivative
named DKO1), also known as (2E)-1-(5-methylfuran-2-yl)-3-(4-nitrophenyl) prop-2-en-1-one, had substantial antibacterial
and biofilm disruptive action. DKO1 effectively shielded against P. aeruginosa-induced inflammation, oxidative stress, lipid
peroxidation, and apoptosis in zebrafish larvae. In adult zebrafish, the treatment enhanced the chances of survivability and
reduced the sickness-like behaviors. Gene expression, biochemical analysis, and histopathology studies found that proinflammatory
cytokines (TNF-α, IL-1β, IL-6, iNOS) were down regulated; antioxidant enzymes such as superoxide dismutase
(SOD) and catalase (CAT) levels increased, and histoarchitecture was restored in zebrafish. The data indicate that DKO1 is
an effective antibacterial agent against P. aeruginosa demonstrated both in vitro and in vivo.
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Candida species cause the most prevalent fungal illness, candidiasis.
Candida albicans is known to cause bloodstream infections.
This species is a commensal bacterium, but it can
cause hospital–acquired diseases, particularly in COVID-19
patients with impaired immune systems. Candida infections
have increased in patients with acute respiratory distress syndrome.
Coumarins are both naturally occurring and synthetically
produced. In this study, the biological activity of 40 coumarin
derivatives was used to create a three-dimensional quantitative
structure activity relationship (3D-QSAR) model. The
training and test minimum inhibitory concentration values
of C. albicans active compounds were split, and a regression
model based on statistical data was established. This model
served as a foundation for the creation of coumarin derivative
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models were confirmed using molecular docking and molecular
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In protein biotechnology, large soluble fusion partners are
widely utilized for increased yield and solubility of recombinant
proteins. However, the production of additional large
fusion partners poses an additional burden to the host, leading
to a decreased protein yield. In this study, we identified
two highly disordered short peptides that were able to increase
the solubility of an artificially engineered aggregationprone
protein, GFP-GFIL4, from 0.6% to 61% (D3-DP00592)
and 46% (D4-DP01038) selected from DisProt database. For
further confirmation, the peptides were applied to two insoluble
E. coli proteins (YagA and YdiU). The peptides also
enhanced solubility from 52% to 90% (YagA) and from 27%
to 93% (YdiU). Their ability to solubilize recombinant proteins
was comparable with strong solubilizing tags, maltosebinding
protein (40 kDa) and TrxA (12 kDa), but much smaller
(< 7 kDa) in size. For practical application, the two peptides
were fused with a restriction enzyme, I-SceI, and they increased
I-SceI solubility from 24% up to 75%. The highly disordered
peptides did not affect the activity of I-SceI while I-SceI fused
with MBP or TrxA displayed no restriction activity. Despite
the small size, the highly disordered peptides were able to
solubilize recombinant proteins as efficiently as conventional
fusion tags and did not interfere with the function of recombinant
proteins. Consequently, the identified two highly disordered
peptides would have practical utility in protein biotechnology
and industry.
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hemorrhagic fever, and dengue shock syndrome. DENV is
transmitted by mosquitoes, Aedes aegypti and A. albopictus,
and is mainly observed in areas where vector mosquitoes live.
The number of dengue cases reported by the World Health
Organization increased more than 8-fold over the last two
decades from 505,430 in 2000 to over 2.4 million in 2010 to
5.2 million in 2019. Although vaccine is the most effective method against DENV, only one commercialized vaccine exists,
and it cannot be administered to children under 9 years of
age. Currently, many researchers are working to resolve the
various problems hindering the development of effective dengue
vaccines; understanding of the viral antigen configuration
would provide insight into the development of effective
vaccines against DENV infection. In this review, the current
status and perspectives on effective vaccine development for
DENV are examined. In addition, a plausible direction for
effective vaccine development against DENV is suggested.
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The poor stability of peptides against trypsin largely limits
their development as potential antibacterial agents. Here, to
obtain a peptide with increased trypsin stability and potent
antibacterial activity, TICbf-14 derived from the cationic peptide
Cbf-14 was designed by the addition of disulfide-bridged
hendecapeptide (CWTKSIPPKPC) loop. Subsequently, the
trypsin stability and antimicrobial and antibiofilm activities
of this peptide were evaluated. The possible mechanisms underlying
its mode of action were also clarified. The results
showed that TICbf-14 exhibited elevated trypsin inhibitory
activity and effectively mitigated lung histopathological damage
in bacteria-infected mice by reducing the bacterial counts,
further inhibiting the systemic dissemination of bacteria and
host inflammation. Additionally, TICbf-14 significantly repressed
bacterial swimming motility and notably inhibited
biofilm formation. Considering the mode of action, we observed
that TICbf-14 exhibited a potent membrane-disruptive
mechanism, which was attributable to its destructive effect
on ionic bridges between divalent cations and LPS of the bacterial
membrane. Overall, TICbf-14, a bifunctional peptide
with both antimicrobial and trypsin inhibitory activity, is
highly likely to become an ideal candidate for drug development
against bacteria.
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RNA metabolism needs to be tightly regulated in response to
changes in cellular physiology. Ribonucleases (RNases) play
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processing, degradation, and recycling of RNA molecules.
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activity at multiple levels, including transcription, post-transcription,
post-translation, and cellular localization. In addition,
various trans-acting regulators of RNase activity have
been discovered in recent years. This review focuses on the
physiological roles and underlying mechanisms of trans-acting
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Multi-omics approaches, including metagenomics and single-
cell amplified genomics, have revolutionized our understanding
of the hidden diversity and function of microbes
in nature. Even in the omics age, cultivation is an essential
discipline in microbial ecology since microbial cultures are
necessary to assess the validity of an in silico prediction about
the microbial metabolism and to isolate viruses infecting bacteria
and archaea. However, the ecophysiological characteristics
of predominant freshwater bacterial lineages remain
largely unknown due to the scarcity of cultured representatives.
In an ongoing effort to cultivate the uncultured majority
of freshwater bacteria, the most abundant freshwater
Actinobacteria acI clade has recently been cultivated from
Lake Soyang through catalase-supplemented high-throughput
cultivation based on dilution-to-extinction. This method
involves physical isolation of target microbes from mixed populations,
culture media simulating natural habitats, and removal
of toxic compounds. In this protocol, we describe detailed
procedures for isolating freshwater oligotrophic microbes,
as well as the essence of the dilution-to-extinction culturing.
As a case study employing the catalase-supplemented
dilution-to-extinction protocol, we also report a cultivation
trial using a water sample collected from Lake Soyang. Of the
480 cultivation wells inoculated with a single lake-water sample,
75 new acI strains belonging to 8 acI tribes (acI-A1, A2,
A4, A5, A6, A7, B1, B4, C1, and C2) were cultivated, and each
representative strain per subclade could be revived from glycerol
stocks. These cultivation results demonstrate that the
protocol described in this study is efficient in isolating freshwater
bacterioplankton harboring streamlined genomes.
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The genome sequences of two pyrene-degrading bacterial
strains of Mycobacterium spp. PYR10 and PYR15, isolated
from the estuarine wetland of the Han river, South Korea,
were determined using the PacBio RS II sequencing platform.
The complete genome of strain PYR15 was 6,037,017 bp in
length with a GC content of 66.5%, and contained 5,933 protein-
coding genes. The genome of strain PYR10 was 5,999,427
bp in length with a GC content of 67.7%, and contained
5,767 protein-coding genes. Based on the average nucleotide
identity values, these strains were designated as M. gilvum
PYR10 and M. pallens PYR15. A genomic comparison
of these pyrene-degrading Mycobacterium strains with pyrene-
non-degrading strains revealed that the genomes of
pyrene-degrading strains possessed similar repertoires of ringhydroxylating
dioxygenases (RHDs), including the pyrenehydroxylating
dioxygenases encoded by nidA and nidA3,
which could be readily distinguished from those of pyrenenon-
degraders. Furthermore, genomic islands, containing
catabolic gene clusters, were shared only among the pyrenedegrading
Mycobacterium strains and these gene clusters
contained RHD genes, including nidAB and nidA3B3. Our
genome data should facilitate further studies on the evolution
of the polycyclic aromatic hydrocarbon-degradation
pathways in the genus Mycobacterium.
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Tuberculosis (TB), caused by Mycobacterium tuberculosis
(Mtb), remains a serious global health problem in the 21st
century because of its high mortality. Mtb is an extremely
successful human-adapted pathogen that displays a multifactorial
ability to control the host immune response and to
evade killing by drugs, resulting in the breakdown of BCG
vaccine-conferred anti-TB immunity and development of
multidrug-resistant (MDR) and extensively drug-resistant
(XDR) Mtb. Although genetic components of the genomes
of the Mtb complex strains are highly conserved, showing
over 99% similarity to other bacterial genera, recently accumulated
evidence suggests that the genetic diversity of the
Mtb complex strains has implications for treatment outcomes,
development of MDR/XDR Mtb, BCG vaccine efficacy,
transmissibility, and epidemiological outbreaks. Thus, new
insights into the pathophysiological features of the Mtb complex
strains are required for development of novel vaccines
and for control of MDR/XDR Mtb infection, eventually leading
to refinement of treatment regimens and the health care
system. Many studies have focused on the differential identification
of Mtb complex strains belonging to different lineages
because of differences in their virulence and geographical
dominance. In this review, we discuss the impact of
differing genetic characteristics among Mtb complex strains
on vaccine efficacy, treatment outcome, development of MDR/
XDR Mtb strains, and epidemiological outbreaks by focusing
on the best-adapted human Mtb lineages. We further
explore the rationale for differential identification of Mtb
strains for more effective control of TB in clinical and laboratory
settings by scrutinizing current diagnostic methods.
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Mycobacterium tuberculosis is the causative agent of tuberculosis
(TB), a major health issue of the present era. The bacterium
inhabits the host macrophage and other immune cells
where it modulates the lysosome trafficking protein, hinders
the formation of phagolysosome, and blocks the TNF receptor-
dependent apoptosis of host macrophage/monocytes.
Other limitations such as resistance to and low bioavailability
and bio-distribution of conventional drugs aid to their high
virulence and human mortality. This review highlights the
use of nanotechnology-based approaches for drug formulation
and delivery which could open new avenues to limit the
pathogenicity of tuberculosis. Moreover phytochemicals, such
as alkaloids, phenols, saponins, steroids, tannins, and terpenoids,
extracted from terrestrial plants and mangroves seem
promising against M. tuberculosis through different molecular
mechanisms. Further understanding of the genomics
and proteomics of this pathogenic microbe could also help
overcome various research gaps in the path of developing a
suitable therapy against tuberculosis.
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Cultivation of the smooth colony Mycobacterium abscessus
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biofilm formation were observed. The amount of glycogpetidolipid
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in GPL synthesis were decreased in the amikacin-treated M.
abscessus strain. An in vitro infection assay revealed that the
amikacin-treated smooth M. abscessus strain induced more
pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) than that
of the smooth strain in murine macrophage cells. These results
suggest that long-term exposure to a low concentration of
amikacin causes a physical change in the cell wall which may
increase its virulence.
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Carbon monoxide dehydrogenase (CO-DH) in Mycobacterium
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to act as nitric oxide dehydrogenase (NO-DH) for the detoxification
of NO. Several accessory genes such as cutD,
cutE, cutF, cutG, cutH, and cutI, are clustered together with
two copies of the CO-DH structural genes (cutB1C1A1 and
cutB2C2A2) in Mycobacterium sp. strain JC1 and are well
conserved in carboxydotrophic mycobacteria. Transcription
of the CO-DH structural and accessory genes was demonstrated
to be increased significantly by acidified sodium nitrate
as a source of NO. A cutI deletion (ΔcutI) mutant of
Mycobacterium sp. strain JC1 was generated to identity the
function of CutI. Lithoautotrophic growth of the ΔcutI mutant
was severely affected in mineral medium supplemented
with CO, while the mutant grew normally with glucose. Western
blotting, CO-DH activity staining, and CO-DH-specific
enzyme assay revealed a significant decrease in the cellular
level of CO-DH in the ΔcutI mutant. Northern blot analysis
and promoter assay showed that expression of the cutB1
and cutB2 genes was significantly reduced at the transcriptional
level in the ΔcutI mutant, compared to that of the wildtype
strain. The ΔcutI mutant was much more susceptible
to NO than was the wild type.
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The conventional methods for diagnosis of tubercular lymphadenitis
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a rapid, sensitive, and specific method for an early diagnosis
of TBLN. Therefore, the present study was conducted
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17, perforin-1, urease, albumin, transferrin, lactoferrin, adenosine
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specificity in distinguishing patients with TB from healthy
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