Robustly detecting mpox and non-mpox using a deep learning framework based on image inpainting.

Due to the lack of efficient mpox diagnostic technology, mpox cases continue to increase. Recently, the great potential of deep learning models in detecting mpox and non-mpox has been proven. However, existing methods are susceptible to interference from various noises in real-world settings, require diverse non-mpox images, and fail to detect abnormal input, which makes them unsuitable for practical deployment and application.

Citrate serves as a signal molecule to modulate carbon metabolism and iron homeostasis in Staphylococcus aureus.

Pathogenic bacteria's metabolic adaptation for survival and proliferation within hosts is a crucial aspect of bacterial pathogenesis. Here, we demonstrate that citrate, the first intermediate of the tricarboxylic acid (TCA) cycle, plays a key role as a regulator of gene expression in Staphylococcus aureus. We show that citrate activates the transcriptional regulator CcpE and thus modulates the expression of numerous genes involved in key cellular pathways such as central carbon metabolism, iron uptake and the synthesis and export of virulence factors.

Bacteriophage protein Dap1 regulates evasion of antiphage immunity and Pseudomonas aeruginosa virulence impacting phage therapy in mice.

Bacteriophages have evolved diverse strategies to overcome host defence mechanisms and to redirect host metabolism to ensure successful propagation. Here we identify a phage protein named Dap1 from Pseudomonas aeruginosa phage PaoP5 that both modulates bacterial host behaviour and contributes to phage fitness. We show that expression of Dap1 in P.

A c-di-GMP signaling module controls responses to iron in Pseudomonas aeruginosa.

Cyclic dimeric guanosine monophosphate (c-di-GMP) serves as a bacterial second messenger that modulates various processes including biofilm formation, motility, and host-microbe symbiosis. Numerous studies have conducted comprehensive analysis of c-di-GMP. However, the mechanisms by which certain environmental signals such as iron control intracellular c-di-GMP levels are unclear.

Modulation of MRSA virulence gene expression by the wall teichoic acid enzyme TarO.

Phenol-soluble modulins (PSMs) and Staphylococcal protein A (SpA) are key virulence determinants for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), an important human pathogen that causes a wide range of diseases. Here, using chemical and genetic approaches, we show that inhibition of TarO, the first enzyme in the wall teichoic acid (WTA) biosynthetic pathway, decreases the expression of genes encoding PSMs and SpA in the prototypical CA-MRSA strain USA300 LAC. Mechanistically, these effects are linked to the activation of VraRS two-component system that directly represses the expression of accessory gene regulator (agr) locus and spa.

The enzyme activity of sortase A is regulated by phosphorylation in .

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 , an important human pathogen, the SrtA is phosphorylated by serine/threonine protein kinase Stk1. SrtA can also be phosphorylated by small-molecule phosphodonor acetyl phosphate (AcP) .

PmiR senses 2-methylisocitrate levels to regulate bacterial virulence in .

To adapt to changes in environmental cues, produces an array of virulence factors to survive the host immune responses during infection. Metabolic products contribute to bacterial virulence; however, only a limited number of these signaling receptors have been explored in detail for their ability to modulate virulence in bacteria. Here, we characterize the metabolic pathway of 2-methylcitrate cycle in and unveil that PmiR served as a receptor of 2-methylisocitrate (MIC) to govern bacterial virulence.

Dual GGDEF/EAL-Domain Protein RmcA Controls the Type III Secretion System of by Interaction with CbrB.

Cyclic diguanylate (-di-GMP) is a major bacterial secondary signaling molecule that controls a multitude of cellular processes. More than 40 genes encoding diguanylate cyclases and phosphodiesterases have been identified in , and many of them have been intensively investigated. However, the mechanism through which they achieve signaling specificity remains unclear.

An Important Role of the Type VI Secretion System of Pseudomonas aeruginosa Regulated by Dnr in Response to Anaerobic Environments.

The type VI secretion system (T6SS) is capable of secreting a variety of metal-binding proteins involved in metal ion uptake, and it mediates an active metal ion transport system that contributes to competition between bacteria. Pseudomonas aeruginosa H2-T6SS can increase molybdenum ion acquisition and enhance bacterial survival advantage by promoting the secretion of the molybdate-binding protein ModA, in which the expression of H2-T6SS core genes , , and is activated by anaerobic conditions and are all regulated by the global regulator Anr. Here, we report the regulation of T6SS by Dnr, a dedicated dissimilatory nitrate respiration regulator in P.

Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics.

Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative opportunistic pathogen that infects patients with cystic fibrosis, burn wounds, immunodeficiency, chronic obstructive pulmonary disorder (COPD), cancer, and severe infection requiring ventilation, such as COVID-19. P.

Regulation of uric acid and glyoxylate metabolism by UgmR protein in Pseudomonas aeruginosa.

The opportunistic pathogen Pseudomonas aeruginosa has evolved several systems to adapt to complex environments. The GntR family proteins play important roles in the regulation of metabolic processes and bacterial pathogenesis. In this study, we uncovered that the gene clusters of PA1513-PA1518 and PA1498-PA1502 in P.

A practical framework RNMF for exploring the association between mutational signatures and genes using gene cumulative contribution abundance.

Background: Mutational signatures are somatic mutation patterns enriching operational mutational processes, which can provide abundant information about the mechanism of cancer. However, understanding of the pathogenic biological processes is still limited, such as the association between mutational signatures and genes.

Methods: We developed a simple and practical R package called RNMF (https://github.

Development and Quantitation of Biofilms after Cultivation in Flow-reactors.

Characterization of biofilm formation and metabolic activities is critical to investigating biofilm interactions with environmental factors and illustrating biofilm regulatory mechanisms. An appropriate model that mimics biofilm habitats therefore demands accurate quantitation and investigation of biofilm-associated activities. Current methodologies commonly involve static biofilm setups (such as biofilm assays in microplates, bead biofilms, or biofilms on glass-slides) and fluidic flow biofilm systems (such as drip-flow biofilm reactors, 3-channel biofilm reactors, or tubing biofilm reactors).

Structural basis for diguanylate cyclase activation by its binding partner in .

Cyclic-di-guanosine monophosphate (c-di-GMP) is an important effector associated with acute-chronic infection transition in . Previously, we reported a signaling network SiaABCD, which regulates biofilm formation by modulating c-di-GMP level. However, the mechanism for SiaD activation by SiaC remains elusive.

Pseudomonas aeruginosa T6SS-mediated molybdate transport contributes to bacterial competition during anaerobiosis.

Type VI secretion system (T6SS) is widely distributed in Gram-negative bacteria and functions as a versatile protein export machinery that translocates effectors into eukaryotic or prokaryotic target cells. Growing evidence indicates that T6SS can deliver several effectors to promote bacterial survival in harmful environments through metal ion acquisition. Here, we report that the Pseudomonas aeruginosa H2-T6SS mediates molybdate (MoO) acquisition by secretion of a molybdate-binding protein, ModA.

The Pyocin Regulator PrtR Regulates Virulence Expression of Pseudomonas aeruginosa by Modulation of Gac/Rsm System and c-di-GMP Signaling Pathway.

In , the second messenger cyclic-di-GMP and Gac/Rsm signaling pathways are associated with the transition from acute to chronic infection. Therefore, identification of the molecular mechanisms that govern lifestyle choice in bacteria is very important. Here, we identified a novel cyclic-di-GMP modulator, PrtR, which was shown to repress pyocin production by inhibition of PrtN and activate the type III secretion system (T3SS) through PtrB.

Mutation-induced remodeling of the BfmRS two-component system in clinical isolates.

Genetic mutations are a primary driving force behind the adaptive evolution of bacterial pathogens. Multiple clinical isolates of , an important human pathogen, have naturally evolved one or more missense mutations in , which encodes the sensor histidine kinase of the BfmRS two-component system (TCS). A mutant BfmS protein containing both the L181P and E376Q substitutions increased the phosphorylation and thus the transcriptional regulatory activity of its cognate downstream response regulator, BfmR.

Iron facilitates the RetS-Gac-Rsm cascade to inversely regulate protease IV (piv) expression via the sigma factor PvdS in Pseudomonas aeruginosa.

Pseudomonas aeruginosa produces several proteases, such as an elastase (LasB protease), a LasA protease, and protease IV (PIV), which are thought as significant virulence factors during infection. Regulators of LasA and LasB expression have been identified and well characterized; however, the molecular details of this regulation of protease IV (PIV) remained largely unknown. Here, we describe the interaction between protease IV and the RetS/Rsm signalling pathway, which plays a central role in controlling the production of multiple virulence factors and the switch from planktonic to biofilm lifestyle.

Impairs Host Defense by Increasing the Quorum-Sensing-Mediated Virulence of .

, found widely in the wild, causes infections in the lungs and several other organs in healthy people but more often in immunocompromised individuals. infection leads to inflammasome assembly, pyroptosis, and cytokine release in the host. OprC is one of the bacterial porins abundant in the outer membrane vesicles responsible for channel-forming and copper binding.

Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR in Pseudomonas aeruginosa.

The GntR family regulators are widely distributed in bacteria and play critical roles in metabolic processes and bacterial pathogenicity. In this study, we describe a GntR family protein encoded by PA4132 that we named MpaR (MvfR-mediated PQS and anthranilate regulator) for its regulation of Pseudomonas quinolone signal (PQS) production and anthranilate metabolism in Pseudomonas aeruginosa. The deletion of mpaR increased biofilm formation and reduced pyocyanin production.

A novel c-di-GMP signal system regulates biofilm formation in .

The bacterial second messenger cyclic-di-GMP (c-di-GMP) controls biofilm formation and other phenotypes relevant to pathogenesis. The human pathogen encodes 17 diguanylate cyclase (DGCs) proteins which are required for c-di-GMP synthesis. Therefore, the c-di-GMP regulatory system in is highly sophisticated.

Alteration of protein homeostasis mediates the interaction of Pseudomonas aeruginosa with Staphylococcus aureus.

Intracellular protein degradation is essential for the survival of all organisms, but its role in interspecies interaction is unknown. Here, we show that the ClpXP protease of Pseudomonas aeruginosa suppresses its antimicrobial activity against Staphylococcus aureus, a common pathogen co-isolated with P. aeruginosa from polymicrobial human infections.

A type VI secretion system delivers a cell wall amidase to target bacterial competitors.

The human pathogen Pseudomonas aeruginosa harbors three paralogous zinc proteases annotated as AmpD, AmpDh2, and AmpDh3, which turn over the cell wall and cell wall-derived muropeptides. AmpD is cytoplasmic and plays a role in the recycling of cell wall muropeptides, with a link to antibiotic resistance. AmpDh2 is a periplasmic soluble enzyme with the former anchored to the inner leaflet of the outer membrane.