Candida albicans is the primary etiological agent associated with candidiasis in humans. Unrestricted growth of C. albicans can progress to systemic infections in the worst situation. This study investigates the antifungal activity of Hydroxychloroquine (HCQ) and mode of action against C. albicans. HCQ inhibited the planktonic growth and yeast to hyphal form morphogenesis of C. albicans significantly at 0.5 mg/ml concentration. The minimum inhibitory concentrations (MIC(50)) of HCQ for C. albicans adhesion and biofilm formation on the polystyrene surface was at 2 mg/ml and 4 mg/ml respectively. Various methods, such as scanning electron microscopy, exploration of the ergosterol biosynthesis pathway, cell cycle analysis, and assessment of S oxygen species (ROS) generation, were employed to investigate HCQ exerting its antifungal effects. HCQ was observed to reduce ergosterol levels in the cell membranes of C. albicans in a dose-dependent manner. Furthermore, HCQ treatment caused a substantial arrest of the C. albicans cell cycle at the G0/G1 phase, which impeded normal cell growth. Gene expression analysis revealed upregulation of SOD2, SOD1, and CAT1 genes after HCQ treatment, while genes like HWP1, RAS1, TEC1, and CDC 35 were downregulated. The study also assessed the in vivo efficacy of HCQ in a mice model, revealing a reduction in the pathogenicity of C. albicans after HCQ treatment. These results indicate that HCQ holds for the development of novel antifungal therapies.
Microbial communities in the rhizosphere play a crucial role
in determining plant growth and crop yield. A few studies
have been performed to evaluate the diversity and co-occurrence
patterns of rhizosphere microbiomes in soybean (Glycine
max) at a regional scale. Here, we used a culture-independent method to compare the bacterial communities of the
soybean rhizosphere between Nebraska (NE), a high-yield
state, and Oklahoma (OK), a low-yield state. It is well known
that the rhizosphere microbiome is a subset of microbes that
ultimately get colonized by microbial communities from the
surrounding bulk soil. Therefore, we hypothesized that differences
in the soybean yield are attributed to the variations in
the rhizosphere microbes at taxonomic, functional, and community
levels. In addition, soil physicochemical properties
were also evaluated from each sampling site for comparative
study. Our result showed that distinct clusters were formed
between NE and OK in terms of their soil physicochemical
property. Among 3 primary nutrients (i.e., nitrogen, phosphorus,
and potassium), potassium is more positively correlated
with the high-yield state NE samples. We also attempted
to identify keystone communities that significantly affected the
soybean yield using co-occurrence network patterns. Network
analysis revealed that communities formed distinct clusters
in which members of modules having significantly positive
correlations with the soybean yield were more abundant in
NE than OK. In addition, we identified the most influential
bacteria for the soybean yield in the identified modules. For
instance, included are class Anaerolineae, family Micromonosporaceae,
genus Plantomyces, and genus Nitrospira in the
most complex module (ME9) and genus Rhizobium in ME23.
This research would help to further identify a way to increase
soybean yield in low-yield states in the U.S. as well as worldwide
by reconstructing the microbial communities in the
rhizosphere.
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The rhizosphere microbiome of 51 potato cultivars with diverse plant growth characteristics Benoit Renaud Martins, Viviane Radl, Krzysztof Treder, Dorota Michałowska, Karin Pritsch, Michael Schloter FEMS Microbiology Ecology.2024;[Epub] CrossRef
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Available antibiotics to treat Acinetobacter baumannii infection
is limited due to increasing resistance and the emergence
of multiple drug-resistant strains. Hence, discovering effective
agents against A. baumannii to reduce the number of infectionrelated
deaths is imperative. In search of novel and alternative
antibiotics, the antibacterial function of lipocalin2 (Lcn2) was
investigated to treat systemic infections of A. baumannii using
a mouse neutropenia model. We observed a significant increase
in serum Lcn2 levels upon bacterial injection into the
mouse, and the administration of recombinant Lcn2 (rmLcn2)
extended their survival. Such protective effects were also observed
in rmLcn2-pretreated macrophages, where rmLcn2
reduced the survival of the pathogen inside the macrophages.
The underlying molecular mechanism of Lcn2 protection was
also investigated. We observed that pretreatment of the Raw-
264.7 macrophages with rmLcn2 markedly altered the expression
of tonB3, which encodes a component of the transporter
for ferrisiderophores in A. baumannii. However, the
expression of katG, the gene encoding catalase, remained unaffected.
These indicate that Lcn2-mediated defense against
the pathogen is related to nutritional immunity rather than
reactive oxygen species (ROS) production. Furthermore, the
addition of rmLcn2 in infected mice diminished bacterial burden
in multiple organs and enhanced the expression of tonB3
in the liver, spleen, and lungs of the infected mice. Increased
survival rate due to rmLcn2 treatment declined when the infection
model was established using lcn2-defective (lcn2-/-)
mice, which indicated the necessity of endogenous Lcn2. Therefore,
the antibacterial function of Lcn2 can be exploited to
develop an alternative therapeutic agent against A. baumannii.
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The COVID-19 pandemic has caused unprecedented health,
social, and economic crises worldwide. However, to date, there
is an only a limited effective treatment for this disease. Human
placenta hydrolysate (hPH) has previously been shown to be
safe and to improve the health condition in patients with hyperferritinemia
and COVID-19. In this study, we aimed to
determine the antiviral effects of hPH against SARS-CoV-2
in vitro and in vivo models and compared with Remdesivir,
an FDA-approved drug for COVID-19 treatment. To assess
whether hPH inhibited SARS-CoV-2 replication, we determined
the CC50, EC50, and selective index (SI) in Vero cells
by infection with a SARS-CoV-2 at an MOI of 0.01. Further,
groups of ferrets infected with 105.8 TCID50/ml of SARS-CoV-2
and treated with hPH at 2, 4, 6 dpi, and compared their clinical
manifestation and virus titers in respiratory tracts with
PBS control-treated group. The mRNA expression of immunerelated
cytokines was determined by qRT-PCR. hPH treatment
attenuated virus replication in a dose-dependent manner in
vitro. In a ferret infection study, treatment with hPH resulted
in minimal bodyweight loss and attenuated virus replication
in the nasal wash, turbinates, and lungs of infected ferrets.
In addition, qRT-PCR results revealed that the hPH treatment
remarkably upregulated the gene expression of type I
(IFN-α and IFN-β) and II (IFN-γ) IFNs in SARS-CoV-2 infected
ferrets. Our data collectively suggest that hPH has antiviral
efficacy against SARS-CoV-2 and might be a promising
therapeutic agent for the treatment of SARS-CoV-2 infection.
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