Virulence

Lumpy skin disease (LSD) was reported for the first time in India in 2019 and since then, it has become endemic. Since a homologous (LSD-virus based) vaccine was not available in the country, goatpox virus (GPV)-based heterologous vaccine was authorized for mass immunization to induce protection against LSD in cattle. This study describes the evaluation of safety, immunogenicity and efficacy of a new live-attenuated LSD vaccine developed by using an Indian field strain, isolated in 2019 from cattle. The virus was attenuated by continuous passage (P=50) in Vero cells...

Sepsis is a leading cause of fatality in invasive candidiasis. The magnitude of the inflammatory response is a determinant of sepsis outcomes, and inflammatory cytokine imbalances are central to the pathophysiological processes. We previously demonstrated that a Candida albicans F1 Fo -ATP synthase α subunit deletion mutant was nonlethal to mice. Here, the potential effects of the F1 Fo -ATP synthase α subunit on host inflammatory responses and the mechanism were studied. Compared with wild-type strain, the F1 Fo -ATP synthase α subunit deletion mutant failed to induce inflammatory responses in Galleria mellonella and murine systemic candidiasis models and significantly decreased the mRNA levels of the proinflammatory cytokines IL-1β, IL-6 and increased those of the anti-inflammatory cytokine IL-4 in the kidney...

The global coronavirus disease 2019 (COVID-19) pandemic has a detrimental impact on public health. COVID-19 usually manifests as pneumonia, which can progress into acute respiratory distress syndrome (ARDS) related to uncontrolled TH17 immune reaction. Currently, there is no effective therapeutic agent to manage COVID-19 with complications. The currently available anti-viral drug remdesivir has an effectiveness of 30% in SARS-CoV-2-induced severe complications. Thus, there is a need to identify effective agents to treat COVID-19 and the associated acute lung injury and other complications...

BACKGROUND: Studies have shown liver aminotransferase level is apparently increased in about 50% of pregnant women with chronic hepatitis B virus (HBV)-infection, which includes acute flares of chronic hepatitis B (CHB). These acute flares of CHB are bound up with immunologic changes that arise during pregnancy and could result in liver dysfunction, hepatic decompensation and even maternal death. However, the indicators for predicting acute flares of CHB among pregnant women still need further study...

Monkeypox (Mpox) was mostly limited to Central and Western Africa, but recently it has been reported globally. The current review presents an update on the virus, including ecology and evolution, possible drivers of transmission, clinical features and management, knowledge gaps, and research priorities to reduce the disease transmission. The origin, reservoir(s) and the sylvatic cycle of the virus in the natural ecosystem are yet to be confirmed. Humans acquire the infection through contact with infected animals, humans, and natural hosts...

Helcococcus ovis (H. ovis) can cause disease in a broad range of animal hosts, including humans, and has been described as an emerging bacterial pathogen in bovine metritis, mastitis, and endocarditis. In this study we developed an infection model that showed H. ovis can proliferate in the hemolymph and induce dose-dependent mortality in the invertebrate model organism Galleria mellonella (G. mellonella) . We applied the model and identified H. ovis isolates with attenuated virulence originating from the uterus of a healthy post-partum dairy cow (KG38) and hypervirulent isolates (KG37, KG106) originating from the uterus of cows with metritis...

Epizootiologists recurrently encounter symbionts and pathobionts in the haemolymph (blood equivalent) of shellfish. One such group is the dinoflagellate genus Hematodinium , which contains several species that cause debilitating disease in decapod crustaceans. The shore crab Carcinus maenas acts as a mobile reservoir of microparasites, including Hematodinium sp. thereby posing a risk to other co-located commercially important species, e.g. velvet crabs ( Necora puber ). Despite the widespread prevalence and documented seasonality of Hematodinium infection dynamics, there is a knowledge gap regarding host-pathogen antibiosis, namely, how Hematodinium avoids the host's immune defences...

Streptococcus agalactiae (GBS) is an important pathogenic bacteria that infected both of human and animals, causing huge economic loss. The increasing cases of antibiotic-resistant GBS impose challenges to treat such infection by antibiotics. Thus, it is highly demanded for the approach to tackle antibiotic resistance in GBS. In this study, we adopte a metabolomic approach to identify the metabolic signature of ampicillin-resistant GBS (AR-GBS) that ampicillin is the routine choice to treat infection by GBS...

Mycobacterium tuberculosis ( M. tb ) utilizes the multifunctionality of its protein factors to deceive the host. The unabated global incidence and prevalence of tuberculosis (TB) and the emergence of multidrug-resistant strains warrant the discovery of novel drug targets that can be exploited to manage TB. This study reports the role of M. tb AAA+ family protein MoxR1 in regulating host-pathogen interaction and immune system functions. We report that MoxR1 binds to TLR4 in macrophage cells and further reveal how this signal the release of proinflammatory cytokines...

Intercellular communication among microbes plays an important role in disease exacerbation. Recent advances have described small vesicles, termed as "extracellular vesicles" (EVs), previously disregarded as "cellular dust" to be vital in the intracellular and intercellular communication in host-microbe interactions. These signals have been known to initiate host damage and transfer of a variety of cargo including proteins, lipid particles, DNA, mRNA and miRNAs. Microbial EVs, referred to generally as "membrane vesicles" (MVs) play a key role in disease exacerbation suggesting their importance in pathogenicity...

We previously demonstrated that MgrA, SarA, SarR, SarS, SarZ, and Rot bind at least three of the four promoters associated with genes encoding primary extracellular proteases in Staphylococcus aureus (Aur, ScpA, SspA/SspB, SplA-F). We also showed that mutation of sarA results in a greater increase in protease production, and decrease in biofilm formation, than mutation of the loci encoding any of these other proteins. However, these conclusions were based on in vitro studies. Thus, the goal of the experiments reported here was to determine the relative impact of the regulatory loci encoding these proteins in vivo ...

Recent viral hemorrhagic fever (VHF) disease outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV) in West Africa are unique and alarming. The intents of this editorial are to highlight what is known about these viruses and the disease outbreaks that they cause in the African continent and elsewhere and to raise awareness of a related virus called Lassa virus (LASV) that causes endemic viral hemorrhagic fever infections and frequent outbreaks in West Africa.

The sucrose non-fermenting 1 ( SNF1 ) complex is a heterotrimeric protein kinase complex that is an ortholog of the mammalian AMPK complex and is evolutionally conserved in most eukaryotes. This complex contains a catalytic subunit (Snf1), a regulatory subunit (Snf4) and a scaffolding subunit (Sip1/Sip2/Gal73) in budding yeast. Although the function of AMPK has been well studied in Saccharomyces cerevisiae and Candida albicans , the role of AMPK in Candida tropicalis has never been investigated. In this study, we focused on SNF4 in C...

Unconventional protein secretion (UPS) plays important roles in cell physiology. In contrast to canonical secretory routes, UPS does not generally require secretory signal sequences and often bypasses secretory compartments such as the ER and the Golgi apparatus.Giardia lamblia is a protist parasite with reduced subcellular complexity which releases several proteins, some of them virulence factors, without canonical secretory signals. This implicates UPS at the parasite-host interface. No dedicated machinery nor mechanism(s) for UPS in Giardia are currently known, although speculations on the involvement of endocytic organelles called PV/PECs, have been put forth...

Polydnaviruses (PDVs), obligatory symbionts with parasitoid wasps, function as host immune suppressors and growth and development regulator. PDVs can induce host hemocyte apoptosis, but the underlying mechanism remains largely unknown. Here, we provided evidence that, during the early stages of parasitism, the activated Cotesia vestalis bracovirus (CvBV) reduced the overall number of host hemocytes by inducing apoptosis. We found that one hemocyte-highly expressed CvBV gene, CvBV-26-4 , could induce hemocyte apoptosis...

In many Gram-positive bacteria, the transpeptidase enzyme sortase A (SrtA) anchors surface proteins to cell wall and plays a critical role in the bacterial pathogenesis. Here, we show that in Staphylococcus aureus , an important human pathogen, the SrtA is phosphorylated by serine/threonine protein kinase Stk1. S. aureus SrtA can also be phosphorylated by small-molecule phosphodonor acetyl phosphate (AcP) in vitro . We determined that various amino acid residues of S. aureus SrtA are subject to phosphorylation, primarily on its catalytic site residue cysteine-184 in the context of a bacterial cell lysate...

Haemophilus parasuis ( H. parasuis ) causes exudative inflammation, implying endothelial dysfunction during pathogen infection. However, so far, the molecular mechanism of endothelial dysfunction caused by H. parasuis has not been clarified. By using the transwell-based cell co-culture system, we demonstrate that knocking out resistin in porcine alveolar macrophages (PAMs) dramatically attenuated endothelial monolayer damage caused by H. parasuis . The resistin secreted by PAMs inhibited the expression of the tight junction proteins claudin-5 and occludin rather than the adherens junction protein VE-cadherin in co-cultured porcine aortic endothelial cells (PAECs)...

The emergence of HIV drug resistance seriously affects the quality of life of patients. However, there has been no extensive study of CSF resistance. The aim of this study is to evaluate common HIV-1 resistance in CSF and compare it with resistance in matched plasma, and analyze the influencing factors of cerebrospinal fluid drug resistance. The matched CSF and plasma samples of 62 HIV-1 patients were tested at one study site in China (Chongqing; 2019-2022). HIV genotyping and drug resistance was evaluated using the Stanford v8...

Mother-to-child transmission (MTCT) is still the main route of hepatitis B virus (HBV) infection. However, the virological factors affecting HBV MTCT have not been fully elucidated. In this study, based on a prospective cohort of mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg), we found that the average nucleotide mutation rate of HBV preS1 promoter (SPI) region in the immunoprophylaxis success group was significantly higher than that in the immunoprophylaxis failure group. Among the nucleotide mutations of the HBV SPI region, the C2729T mutation had the highest frequency...

We previously demonstrated that two methyltransferase motifs, K-D-K-E and G-G-D, affect the pathogenicity of Newcastle disease virus (NDV) by regulating mRNA translation and virus transmission. Here, we compared the infectious centre area produced by the NDV strain, rSG10, and methyltransferase motifs mutant rSG10 strains in DF-1 cells. The results show that intercellular transmission was attenuated by methyltransferase motif mutations. We further determined the ability of mutant viruses to spread in cell-free and cell-to-cell situations...