cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.29567345.v1
title: Carnosol attenuates <i>Acinetobacter baumannii</i> virulence by interfering with indole-mediated quorum sensing

description: Many bacterial pathogens utilize quorum sensing (QS) signals to modulate the biological functions in a cell density-dependent manner. <i>Acinetobacter baumannii</i> is a harmful pathogen and a major cause of hospital-acquired infections due to its severe drug-resistance and pathogenic nature. Therefore, the development of innovative antibacterial strategies for <i>A. baumannii</i> infections is important. Earlier studies have proved that <i>A. baumannii</i> utilizes N-acyl-L-homoserine lactones (AHLs) and indole signalling systems to modulate its biological functions and virulence. Here, we report that carnosol, which is isolated from <i>Salvia officinalis</i> L. (<i>S. officinalis</i>), inhibited the pathogenicity of <i>A. baumannii</i> by interfering with indole-mediated quorum sensing. Phenotypic and virulence experiments have revealed that carnosol decreased the formation of biofilms, motility, and cytotoxicity of <i>A. baumannii</i>, without affecting its growth rate. Genetic and biochemical analysis results showed that carnosol reduced the regulatory effect of AbiR on the transcription of target genes by inhibiting the binding of AbiR to the promoters of these genes. Our results suggest that the indole QS system of <i>A. baumannii</i> could be used as a new target and that carnosol might be developed as a new anti-virulence agent against <i>A. baumannii</i> infections.
DOI: 10.6084/m9.figshare.28366918
title: Guanosine enhances the bactericidal effect of ceftiofur sodium on <i>Streptococcus suis</i> by activating bacterial metabolism

description: The emergence and rapid development of antibiotic resistance poses a serious threat to global public health. <i>Streptococcus suis</i> (<i>S. suis</i>) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against multidrug-resistant bacteria. However, the mechanism by which metabolites act as antibiotic adjuvant remains unclear. Here, we found that guanosine metabolism was repressed in multidrug-resistant <i>S. suis</i>. Exogenous guanosine promoted the antibacterial effects of ceftiofur sodium (CEF) <i>in vitro</i> and <i>in vivo</i>. Furthermore, we demonstrated that exogenous guanosine promoted the biosynthesis of purine pathway, TCA cycle and bacterial respiration, which make bacteria more sensitive to the killing effect of antibacterial. In addition, the function of the cell membrane is affected by guanosine and the accumulation of antimicrobials in the bacteria increased. Bacterial-oxidative stress and DNA damage induced by guanosine is also one of the mechanisms by which the antibacterial effect is enhanced. These results suggest that guanosine is a promising adjuvant for antibacterial drugs and provide new theoretical basis for the clinical treatment of <i>S. suis</i> infection.
DOI: 10.6084/m9.figshare.28366918.v1
title: Guanosine enhances the bactericidal effect of ceftiofur sodium on <i>Streptococcus suis</i> by activating bacterial metabolism

description: The emergence and rapid development of antibiotic resistance poses a serious threat to global public health. <i>Streptococcus suis</i> (<i>S. suis</i>) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against multidrug-resistant bacteria. However, the mechanism by which metabolites act as antibiotic adjuvant remains unclear. Here, we found that guanosine metabolism was repressed in multidrug-resistant <i>S. suis</i>. Exogenous guanosine promoted the antibacterial effects of ceftiofur sodium (CEF) <i>in vitro</i> and <i>in vivo</i>. Furthermore, we demonstrated that exogenous guanosine promoted the biosynthesis of purine pathway, TCA cycle and bacterial respiration, which make bacteria more sensitive to the killing effect of antibacterial. In addition, the function of the cell membrane is affected by guanosine and the accumulation of antimicrobials in the bacteria increased. Bacterial-oxidative stress and DNA damage induced by guanosine is also one of the mechanisms by which the antibacterial effect is enhanced. These results suggest that guanosine is a promising adjuvant for antibacterial drugs and provide new theoretical basis for the clinical treatment of <i>S. suis</i> infection.
DOI: 10.6084/m9.figshare.30621820
title: Cytochrome bd-II oxidase CyxA promotes the pathogenicity of <i>Klebsiella pneumoniae</i> by resisting oxidative stress

description: Adaptation to oxidative stress is crucial for survival of <i>Klebsiella pneumoniae</i> in external environments and within infected hosts. Cytochrome bd oxidase contributes to oxidative stress resistance and enhances the pathogenicity of several pathogens. In this study, we explored the role of cytochrome bd-II oxidase CyxA in <i>K. pneumoniae</i>’s response to oxidative stress and its overall pathogenicity. The expression level of <i>cyxA</i> was significantly increased in response to oxidative stress in the wild-type strain (WT). Deletion of <i>cyxA</i> reduced <i>K. pneumoniae</i>’s resistance to exogenous hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and nitric oxide (NO). Additionally, the expression levels of <i>cyxA</i> at 37°C and 41°C were significantly higher compared to 30°C, and the Δ<i>cyxA</i> strain exhibited significantly lower viable counts, elevated intracellular reactive oxygen species (ROS) levels, and decreased total antioxidant capacity (T-AOC) relative to WT at 37°C and 41°C. Results from intraperitoneal and intestinal infection models in mice revealed that CyxA promotes pathogenicity by enhancing the invasiveness of <i>K. pneumoniae</i> into intra-abdominal tissues and confers a fitness advantage in the inflamed gut. Moreover, we provide preliminary evidence that CyxA exhibits catalase activity and increases the expression of catalase KatE. In summary, our results suggest that cytochrome bd-II oxidase CyxA enhances <i>K. pneumoniae</i>’s resistance to oxidative stress caused by exogenous ROS, elevated temperature, and inflammation, either by directly or indirectly metabolizing H<sub>2</sub>O<sub>2</sub>, thereby promoting its growth and pathogenicity.
DOI: 10.6084/m9.figshare.30621820.v2
title: Cytochrome bd-II oxidase CyxA promotes the pathogenicity of <i>Klebsiella pneumoniae</i> by resisting oxidative stress

description: Adaptation to oxidative stress is crucial for survival of <i>Klebsiella pneumoniae</i> in external environments and within infected hosts. Cytochrome bd oxidase contributes to oxidative stress resistance and enhances the pathogenicity of several pathogens. In this study, we explored the role of cytochrome bd-II oxidase CyxA in <i>K. pneumoniae</i>’s response to oxidative stress and its overall pathogenicity. The expression level of <i>cyxA</i> was significantly increased in response to oxidative stress in the wild-type strain (WT). Deletion of <i>cyxA</i> reduced <i>K. pneumoniae</i>’s resistance to exogenous hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and nitric oxide (NO). Additionally, the expression levels of <i>cyxA</i> at 37°C and 41°C were significantly higher compared to 30°C, and the Δ<i>cyxA</i> strain exhibited significantly lower viable counts, elevated intracellular reactive oxygen species (ROS) levels, and decreased total antioxidant capacity (T-AOC) relative to WT at 37°C and 41°C. Results from intraperitoneal and intestinal infection models in mice revealed that CyxA promotes pathogenicity by enhancing the invasiveness of <i>K. pneumoniae</i> into intra-abdominal tissues and confers a fitness advantage in the inflamed gut. Moreover, we provide preliminary evidence that CyxA exhibits catalase activity and increases the expression of catalase KatE. In summary, our results suggest that cytochrome bd-II oxidase CyxA enhances <i>K. pneumoniae</i>’s resistance to oxidative stress caused by exogenous ROS, elevated temperature, and inflammation, either by directly or indirectly metabolizing H<sub>2</sub>O<sub>2</sub>, thereby promoting its growth and pathogenicity.
DOI: 10.6084/m9.figshare.29464312
title: Emergence of highly virulent <i>Aeromonas dhakensis</i> in channel catfish aquaculture: Genomic insights into pathogenicity and antimicrobial resistance

description: <i>Aeromonas dhakensis</i> has emerged as a significant pathogen in aquaculture, causing severe disease outbreaks and resulting in substantial economic losses. However, its pathogenic mechanism and virulence factors remain largely unexplored. In this study, we isolated a highly virulent strain of <i>A. dhakensis</i>, CWH5, from a severe disease outbreak in farmed channel catfish (<i>Ictalurus punctatus</i>). Through comprehensive whole-genome analysis, we elucidated its pathogenicity and the genetic basis for its high virulence and multi-antimicrobial resistance in channel catfish. Experimental infections showed that CWH5 exhibited exceptional virulence, with an LD<sub>50</sub> of (5.37 ± 0.31) ×10<sup>5</sup> CFU/fish and causing 100% mortality within 24 h at a concentration of 10<sup>7</sup> CFU/fish. Histopathological examinations revealed severe multi-organ damage, including extensive hepatocellular necrosis, gill epithelial destruction, and fin tissue deterioration. Whole-genome sequencing revealed a 4.92 Mb circular chromosome encoding sophisticated virulence mechanisms, such as complete Type III, IV, and VI secretion systems, and a vast arsenal of 60 antibiotic resistance genes across 15 drug classes. Comparative genomic analysis positioned CWH5 within the <i>A. dhakensis</i> clade, sharing the highest sequence similarity with <i>A. dhakensis</i> CIP 107,500<sup>T</sup>. The co-localization of virulence and resistance determinants within mobile genetic elements suggests the potential for horizontal gene transfer. Our work underscored the importance of <i>A. dhakensis</i> CWH5 as an emerging pathogen in channel catfish aquaculture, providing crucial insights into the molecular mechanisms of its exceptional virulence and implying significant implications for disease management and antimicrobial resistance surveillance in aquaculture settings.
DOI: 10.6084/m9.figshare.29464312.v1
title: Emergence of highly virulent <i>Aeromonas dhakensis</i> in channel catfish aquaculture: Genomic insights into pathogenicity and antimicrobial resistance

description: <i>Aeromonas dhakensis</i> has emerged as a significant pathogen in aquaculture, causing severe disease outbreaks and resulting in substantial economic losses. However, its pathogenic mechanism and virulence factors remain largely unexplored. In this study, we isolated a highly virulent strain of <i>A. dhakensis</i>, CWH5, from a severe disease outbreak in farmed channel catfish (<i>Ictalurus punctatus</i>). Through comprehensive whole-genome analysis, we elucidated its pathogenicity and the genetic basis for its high virulence and multi-antimicrobial resistance in channel catfish. Experimental infections showed that CWH5 exhibited exceptional virulence, with an LD<sub>50</sub> of (5.37 ± 0.31) ×10<sup>5</sup> CFU/fish and causing 100% mortality within 24 h at a concentration of 10<sup>7</sup> CFU/fish. Histopathological examinations revealed severe multi-organ damage, including extensive hepatocellular necrosis, gill epithelial destruction, and fin tissue deterioration. Whole-genome sequencing revealed a 4.92 Mb circular chromosome encoding sophisticated virulence mechanisms, such as complete Type III, IV, and VI secretion systems, and a vast arsenal of 60 antibiotic resistance genes across 15 drug classes. Comparative genomic analysis positioned CWH5 within the <i>A. dhakensis</i> clade, sharing the highest sequence similarity with <i>A. dhakensis</i> CIP 107,500<sup>T</sup>. The co-localization of virulence and resistance determinants within mobile genetic elements suggests the potential for horizontal gene transfer. Our work underscored the importance of <i>A. dhakensis</i> CWH5 as an emerging pathogen in channel catfish aquaculture, providing crucial insights into the molecular mechanisms of its exceptional virulence and implying significant implications for disease management and antimicrobial resistance surveillance in aquaculture settings.
DOI: 10.6084/m9.figshare.29979553
title: Hemocyanin controls <i>Vibrio</i> levels in hemolymph by modulating intracellular ROS via p38 MAPK

description: Redox reactions are essential for various biological processes, hence, maintaining redox homeostasis is critical for cellular health and host–microbe interactions, particularly in marine invertebrates, where these processes remain poorly understood. This study investigates the role of the respiratory protein hemocyanin in regulating redox-related genes, reactive oxygen species (ROS) levels in shrimp hemocytes, and its influence on immune function and hemolymph <i>Vibrio</i> abundance. Our results show that hemocyanin is crucial in the regulation of the redox system, as hemocyanin knockdown disrupts the expression of antioxidant (<i>Pv</i>POD and <i>Pv</i>GPX) and pro-oxidant (<i>Pv</i>XOX) genes and redox enzyme activities, leading to elevated ROS levels in hemocytes. Additionally, we found that hemocyanin controls redox homeostasis in hemocytes through the p38-MAPK-c-Jun signaling pathway. Moreover, ROS levels regulated by hemocyanin via the MAPK pathway impacted on hemolymph <i>Vibrio</i> spp. abundance. These findings highlight a crucial role of hemocyanin as an antioxidant that modulates redox balance in shrimp hemocytes, with significant implications for immune defense and microbial homeostasis, offering new insights into antioxidative mechanisms in marine invertebrates.
DOI: 10.6084/m9.figshare.30621820.v1
title: Cytochrome bd-II oxidase CyxA promotes the pathogenicity of <i>klebsiella pneumoniae</i> by resisting oxidative stress

description: Adaptation to oxidative stress is crucial for survival of <i>Klebsiella pneumoniae</i> in external environments and within infected hosts. Cytochrome bd oxidase contributes to oxidative stress resistance and enhances the pathogenicity of several pathogens. In this study, we explored the role of cytochrome bd-II oxidase CyxA in <i>K. pneumoniae</i>’s response to oxidative stress and its overall pathogenicity. The expression level of <i>cyxA</i> was significantly increased in response to oxidative stress in the wild-type strain (WT). Deletion of <i>cyxA</i> reduced <i>K. pneumoniae</i>’s resistance to exogenous hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and nitric oxide (NO). Additionally, the expression levels of <i>cyxA</i> at 37 °C and 41 °C were significantly higher compared to 30 °C, and the Δ<i>cyxA</i> strain exhibited significantly lower viable counts, elevated intracellular reactive oxygen species (ROS) levels, and decreased total antioxidant capacity (T-AOC) relative to WT at 37 °C and 41 °C. Results from intraperitoneal and intestinal infection models in mice revealed that CyxA promotes pathogenicity by enhancing the invasiveness of <i>K. pneumoniae</i> into intra-abdominal tissues and confers a fitness advantage in the inflamed gut. Moreover, we provide preliminary evidence that CyxA exhibits catalase activity and increases the expression of catalase KatE. In summary, our results suggest that cytochrome bd-II oxidase CyxA enhances <i>K. pneumoniae</i>’s resistance to oxidative stress caused by exogenous ROS, elevated temperature, and inflammation, either by directly or indirectly metabolizing H<sub>2</sub>O<sub>2</sub>, thereby promoting its growth and pathogenicity.
DOI: 10.6084/m9.figshare.29979553.v1
title: Hemocyanin controls <i>Vibrio</i> levels in hemolymph by modulating intracellular ROS via p38 MAPK

description: Redox reactions are essential for various biological processes, hence, maintaining redox homeostasis is critical for cellular health and host–microbe interactions, particularly in marine invertebrates, where these processes remain poorly understood. This study investigates the role of the respiratory protein hemocyanin in regulating redox-related genes, reactive oxygen species (ROS) levels in shrimp hemocytes, and its influence on immune function and hemolymph <i>Vibrio</i> abundance. Our results show that hemocyanin is crucial in the regulation of the redox system, as hemocyanin knockdown disrupts the expression of antioxidant (<i>Pv</i>POD and <i>Pv</i>GPX) and pro-oxidant (<i>Pv</i>XOX) genes and redox enzyme activities, leading to elevated ROS levels in hemocytes. Additionally, we found that hemocyanin controls redox homeostasis in hemocytes through the p38-MAPK-c-Jun signaling pathway. Moreover, ROS levels regulated by hemocyanin via the MAPK pathway impacted on hemolymph <i>Vibrio</i> spp. abundance. These findings highlight a crucial role of hemocyanin as an antioxidant that modulates redox balance in shrimp hemocytes, with significant implications for immune defense and microbial homeostasis, offering new insights into antioxidative mechanisms in marine invertebrates.
DOI: 10.6084/m9.figshare.30477707
title: Antigenicity in mice of a recombinant <i>Neisseria gonorrhoeae</i> MafA 2/3 protein

description: There are no prophylactic vaccines for preventing the disease gonorrhea, caused by sexually transmitted infection with the Gram-negative pathogen <i>Neisseria gonorrhoeae</i>. In this study, we examined the antigenicity in mice of a recombinant rMafA 2/3 outer membrane protein (OMP). Mice were immunized with rMafA 2/3 with different adjuvants and delivery vehicles, which induced high levels of antibody that recognized the MafA 2/3 protein in i) antigen and OM-ELISA, ii) OM-western blots and iii) on whole bacteria examined with flow cytometry. Antisera to rMafA 2/3 in liposomes with monophosphoryl lipid A (MPLA) and with Zwittergent 3–14 ± MPLA, were bactericidal <i>in vitro</i> for homologous P9-17 (Allele 193) gonococcal strain (median 50% bactericidal titers of 256). Analysis of MafA 2/3 alleles among gonococcal isolates in the PubMLST database showed that ~50% and 26% of gonococci expressed Allele 90 and Allele 88-encoded protein respectively, and these proteins were identical bar one amino acid substitution. Murine antisera to Allele 193 rMafA 2/3 expressing strain P9-17 (~98% homology with Alleles 88/90 MafA 2/3 protein) showed bactericidal activity against heterologous strain FA1090 (Allele 88, 50% median titers from 4 to 64), but not to heterologous strain AR205 (Allele 90). By contrast, a rabbit anti-rMafA 2/3 serum was bactericidal for P9-17, FA1090, and AR205 (50% titers of 2048–4096), and inhibited significantly (<i>p</i> &lt;0.05) the association of gonococci to human Chang conjunctival epithelial cells <i>in vitro</i>. These findings suggest that MafA 2/3 could be a promising OMP for further study as a component of future subunit gonococcal vaccines.
DOI: 10.6084/m9.figshare.30477707.v1
title: Antigenicity in mice of a recombinant <i>Neisseria gonorrhoeae</i> MafA 2/3 protein

description: There are no prophylactic vaccines for preventing the disease gonorrhea, caused by sexually transmitted infection with the Gram-negative pathogen <i>Neisseria gonorrhoeae</i>. In this study, we examined the antigenicity in mice of a recombinant rMafA 2/3 outer membrane protein (OMP). Mice were immunized with rMafA 2/3 with different adjuvants and delivery vehicles, which induced high levels of antibody that recognized the MafA 2/3 protein in i) antigen and OM-ELISA, ii) OM-western blots and iii) on whole bacteria examined with flow cytometry. Antisera to rMafA 2/3 in liposomes with monophosphoryl lipid A (MPLA) and with Zwittergent 3–14 ± MPLA, were bactericidal <i>in vitro</i> for homologous P9-17 (Allele 193) gonococcal strain (median 50% bactericidal titers of 256). Analysis of MafA 2/3 alleles among gonococcal isolates in the PubMLST database showed that ~50% and 26% of gonococci expressed Allele 90 and Allele 88-encoded protein respectively, and these proteins were identical bar one amino acid substitution. Murine antisera to Allele 193 rMafA 2/3 expressing strain P9-17 (~98% homology with Alleles 88/90 MafA 2/3 protein) showed bactericidal activity against heterologous strain FA1090 (Allele 88, 50% median titers from 4 to 64), but not to heterologous strain AR205 (Allele 90). By contrast, a rabbit anti-rMafA 2/3 serum was bactericidal for P9-17, FA1090, and AR205 (50% titers of 2048–4096), and inhibited significantly (<i>p</i> &lt;0.05) the association of gonococci to human Chang conjunctival epithelial cells <i>in vitro</i>. These findings suggest that MafA 2/3 could be a promising OMP for further study as a component of future subunit gonococcal vaccines.
DOI: 10.6084/m9.figshare.30577009
title: Targeting methicillin-resistant <i>Staphylococcus aureus</i>: The comprehensive action of ent-kaurane diterpenoids on bacterial integrity

description: Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) represents a considerable challenge to global health owing to its resistance to antibiotics. In our prior research, we identified four ent-kaurane diterpenoids (compounds <b>1–4</b>) isolated from <i>Siegesbeckia orientalis</i> L., which exhibited anti-MRSA activity. Nevertheless, the precise mechanisms by which these compounds exert their effects remain to be fully elucidated. This study aims to comprehensively evaluate the anti-MRSA properties and explore the biological processes associated with the activity of compounds <b>1–4</b>. We utilized the minimum broth dilution method, electron microscopy, and membrane integrity assays to demonstrate that these compounds inhibit the growth of MRSA by disrupting cell wall and membrane structures. Additionally, crystal violet staining confirmed their efficacy in disrupting mature biofilms. In a murine model of bacteremia, the tested compounds <b>1–4</b> demonstrated a reduction in septic symptoms and exhibited favorable biosafety profiles, with compound <b>1</b> showing the most significant antibacterial effects. Transcriptomic analysis indicated that compound <b>1</b> disrupts peptidoglycan synthesis and interferes with the metabolism of cell wall precursors. Furthermore, it modulates the expression of genes associated with ion transport and membrane-related metabolic enzymes, thereby compromising the integrity of both the cell wall and the cytoplasmic membrane. In conclusion, this study systematically characterizes the anti-MRSA activity of the diterpenoid components derived from S. <i>orientalis</i> and identifies key biological processes and gene expression changes linked to their effects, and presents a promising new strategy for the development of natural anti-MRSA pharmaceuticals.