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Frontiers in Microbiology 2023Rat species , also known as the brown street rat, is the most abundant mammal after humans in urban areas, where they co-exist with humans and domestic animals. The...
Rat species , also known as the brown street rat, is the most abundant mammal after humans in urban areas, where they co-exist with humans and domestic animals. The reservoir role of of zoonotic pathogens in cities among rodent-borne diseases that could endanger the lives of humans and other mammals. Therefore, understanding the normal microbiome of is crucial for understanding and preventing zoonotic pathogen transmission to humans and animals. We investigated the intestinal microbiome of free-living collected from the Ruili, Nujiang, and Lianhe regions of Yunnan, China, using 16S rRNA gene sequence analysis. Proteobacteria, followed by Firmicutes, and Bacteroidetes were abundant in the intestines of ; however, bacterial compositions varied significantly between samples from different locations. Following a similar trend, Gammaproteobacteria, Bacilli, and Clostridia were among the top bacterial classes in most intestinal samples. The situation differed slightly for the Lianhe and Nujiang samples, although Phyla Bacteroidota and Spirochaetota were most prevalent. The Alpha diversity, Chao1, and Simpson indexes revealed microbial richness among the samples. A slight variation was observed among the samples collected from Ruili, Nujiang, and Lianhe. At species levels, several opportunistic and zoonotic bacterial pathogens, including , , , , , , etc., were revealed in the intestines, implying the need for a regular survey to monitor and control rodent populations. In conclusion, we explored diverse microbial communities in intestines captured from different regions. Further, we identified several opportunistic and potential bacterial pathogens, which still need to be tested for their underlying pathogenesis. The findings of our current study should be considered a warning to the health authorities to implement rat control and surveillance strategies globally.
PubMed: 38029126
DOI: 10.3389/fmicb.2023.1283453 -
Frontiers in Veterinary Science 2023The deletion of orphan response regulator CovR reduces the growth rate of serotype 2 ( 2). In this study, metabolome and transcriptome profiling were performed to study...
The deletion of orphan response regulator CovR reduces the growth rate of serotype 2 ( 2). In this study, metabolome and transcriptome profiling were performed to study the mechanisms underlying the poor growth of 2 caused by the deletion of orphan response regulator CovR. By comparing 2 (Δ) and 2 (SC19), 146 differentially accumulated metabolites (upregulated: 83 and downregulated: 63) and 141 differentially expressed genes (upregulated: 86 and downregulated: 55) were identified. Metabolome and functional annotation analysis revealed that the growth of Δ was inhibited by the imbalance aminoacyl tRNA biosynthesis (the low contents of L-lysine, L-aspartic acid, L-glutamine, and L-glutamic acid, and the high content of L-methionine). These results provide a new insight into the underlying poor growth of 2 caused by the deletion of orphan response regulator CovR. Metabolites and candidate genes regulated by the orphan response regulator CovR and involved in the growth of 2 were reported in this study.
PubMed: 38026618
DOI: 10.3389/fvets.2023.1280161 -
Journal of Pharmaceutical Analysis Oct 2023Muramidase-released protein (MRP) is now being recognized as a critical indicator of the virulence and pathogenicity of (). However, the identification of viable...
Muramidase-released protein (MRP) is now being recognized as a critical indicator of the virulence and pathogenicity of (). However, the identification of viable therapeutics for infection was hindered by the absence of an explicit mechanism for MRP-actuated inflammation. Dihydroartemisinin (DhA) is an artemisinin derivative with potential anti-inflammatory activity. The modulatory effect of DhA on the inflammatory response mediated by the virulence factor MRP remains obscure. This research aimed to identify the signaling mechanism by which MRP triggers the innate immune response in mouse spleen and cultured macrophages. With the candidate mechanism in mind, we investigated DhA for its ability to dampen the pro-inflammatory response induced by MRP. The innate immune response in mice was drastically triggered by MRP, manifesting as splenic and systemic inflammation with splenomegaly, immune cell infiltration, and an elevation in pro-inflammatory cytokines. A crucial role for Toll-like receptor 4 (TLR4) in coordinating the MRP-mediated inflammatory response via nuclear factor-kappa B (NF-κB) activation was revealed by TLR4 blockade. In addition, NF-κB-dependent transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinases (MAPKs) activation was required for the inflammatory signal transduction engendered by MRP. Intriguingly, we observed an alleviation effect of DhA on the MRP-induced immune response, which referred to the suppression of TLR4-mediated actuation of NF-κB-STAT3/MAPK cascades. The inflammatory response elicited by MRP is relevant to TLR4-dependent NF-κB activation, followed by an increase in the activity of STAT3 or MAPKs. DhA mitigates the inflammation process induced by MRP via blocking the TLR4 cascade, highlighting the therapeutic potential of DhA in targeting infection diseases.
PubMed: 38024861
DOI: 10.1016/j.jpha.2023.05.013 -
Translational Animal Science 2023() is an endemic zoonotic pathogen still lacking adequate prevention in pigs. The present case study looked back to the occurrence and consequences of outbreaks in our...
() is an endemic zoonotic pathogen still lacking adequate prevention in pigs. The present case study looked back to the occurrence and consequences of outbreaks in our swine research facilities in search of new metabolic and physiological insight. From a series of outbreaks, a dataset was created including 56 pigs sampled during disease detection based on clinical signs. Pigs suspected with infection were defined as diseased ( = 28) and included pigs defined as neurologically diseased ( = 20) when severe neurological signs (central nervous system dysfunctions, i.e., opisthotonos, ataxia, and generalized tremor) were observed. Another set of 28 pigs included respective pen mates from each case and were defined as control. Representative deaths were confirmed to be caused by Tonsillar swabs were collected and analyzed by quantitative polymerase chain reaction () for total bacteria, total , and serotypes () 2 (and/or 1/2) and 9. Blood and sera were analyzed to quantify blood gases, minerals, and reactive immunoglobulins against current isolates. Data collected included litter sibling associations, birth and weaning body weight (), and average daily gain () 7 d after the disease detection. In general, the disease increased pH, sO and the incidence of alkalosis, but reduced pCO, glucose, Ca, P, Mg, K, and Na in blood/serum compared to control. The SS2 (and/or SS1/2) prevalence was significantly ( < 0.05) increased in neurologically diseased pigs and its relative abundance tended ( < 0.10) to increase in tonsils. In contrast, the relative abundance of total was lower ( > 0.05) in diseased pigs than control pigs. Levels of reactive IgG2 were lower, but IgM were higher ( < 0.03) in neurologically affected pigs compared to control. Furthermore, there was an increased proportion of sibling pigs that were diseased compared to control. In conclusion, our results evidence that naturally affected pigs were associated to average performing pigs without any predisease trait to highlight but a sow/litter effect. Besides, neurologically affected pigs had increased (SS2 and/or 1/2) prevalence and relative abundance, a respiratory alkalosis profile, and mineral loss.
PubMed: 38023423
DOI: 10.1093/tas/txad126 -
Virulence Dec 2023is a zoonotic Gram-positive bacterium that causes invasive infections such as sepsis and meningitis, threatening public health worldwide. For successful establishment...
is a zoonotic Gram-positive bacterium that causes invasive infections such as sepsis and meningitis, threatening public health worldwide. For successful establishment of infection, the bacterium should subvert the innate effectors of immune defence, including the cathelicidin family of host-defence peptides that combat pathogenic bacteria by directly disrupting cell membranes and coordinating immune responses. Here, our study shows that an extracellular endopeptidase O (PepO) of contributes to assisting the bacterium to resist cathelicidin-mediated killing, as the deletion of the gene makes more sensitive to the human cathelicidin LL-37, as well as its mouse equivalent, mCRAMP. This protease targets and cleaves both LL-37 and mCRAMP, degrading them into shorter peptides with only a few amino acids, thereby abrogating their ability to kill . By cleaving LL-37 and mCRAMP, PepO impairs their chemotactic properties for neutrophil migration and undermines their anti-apoptosis activity, which is required for prolonging neutrophil lifespan. Also, PepO inhibits the ability of LL-37 and mCRAMP to promote lysosome development in macrophages. Moreover, the loss of PepO attenuates organ injury and decreases bacterial burdens in a murine model of bacteraemia. Taken together, these data provide novel insights into the role of the intrinsic proteolytic characteristics of PepO in -host interaction. Our findings demonstrate that utilizes the PepO protease to cleave cathelicidins, which is an immunosuppressive strategy adopted by this bacterium to facilitate pathogenesis.
Topics: Animals; Humans; Mice; Cathelicidins; Antimicrobial Cationic Peptides; Immune Evasion; Streptococcus suis; Metalloendopeptidases; Bacteria
PubMed: 38010345
DOI: 10.1080/21505594.2023.2283896 -
Pathogens (Basel, Switzerland) Nov 2023serotype 2 is an important swine bacterial pathogen causing sudden death, septic shock, and meningitis. However, serotype 2 strains are phenotypically and genotypically...
serotype 2 is an important swine bacterial pathogen causing sudden death, septic shock, and meningitis. However, serotype 2 strains are phenotypically and genotypically heterogeneous and composed of a multitude of sequence types (STs) whose distributions greatly vary worldwide. It has been previously shown that the lipoprotein (LPP) maturation enzymes diacylglyceryl transferase (Lgt) and signal peptidase (Lsp) significantly modulate the inflammatory host response and play a differential role in virulence depending on the genetic background of the strain. Differently from Eurasian ST1/ST7 strains, the capsular polysaccharide of a North American serotype 2 ST25 representative strain only partially masks sub-capsular domains and bacterial wall components. Thus, our hypothesis is that since LPPs would be more surface exposed in ST25 strains than in their ST1 or ST7 counterparts, the maturation enzymes would play a more important role in the pathogenesis of the infection caused by the North American strain. Using isogenic Δ and Δ mutants derived from the wild-type ST25 strain, our studies suggest that these enzymes do not seem to play a role in the interaction between and epithelial and endothelial cells, regardless of the genetics background of the strain used. However, a role in the formation of biofilms (also independently of the STs) has been demonstrated. Moreover, the involvement of LPP dendritic cell activation in vitro seems to be somehow more pronounced with the ST25 strain. Finally, the Lgt enzyme seems to play a more important role in the virulence of the ST25 strain. Although some differences between STs could be observed, our original hypothesis that LPPs would be significantly more important in ST25 strains due to a better bacterial surface exposition could not be confirmed.
PubMed: 38003790
DOI: 10.3390/pathogens12111325 -
BMC Veterinary Research Nov 2023Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen. Orphan response regulator CovR plays crucial regulative functions in the survivability and...
BACKGROUND
Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen. Orphan response regulator CovR plays crucial regulative functions in the survivability and pathogenicity of S. suis 2. However, research on the CovR in S. suis 2 is limited.
RESULTS
In this study, the regulative functions of CovR in the survivability and pathogenicity were investigated in S. suis 2 isolated from a diseased pig. The deletion of CovR significantly weakened the survivability and pathogenicity of S. suis 2. Compared with the wild-type strain, ΔcovR showed slower growth rates and thinner capsular polysaccharides. Moreover, ΔcovR showed reduced adhesion and invasion to Hep-2 cells as well as anti-phagocytosis and anti-killing ability to 3D4 cells and anti-serum killing ability. In addition, the deletion of CovR significantly reduced the colonisation ability of S. suis 2 in mice. The survival rate of mice infected with ΔcovR was increased by 16.7% compared with that of mice infected with S. suis 2. Further, the deletion of CovR led to dramatic changes in metabolism-related pathways in S. suis 2, five of those, including fructose and mannose metabolism, glycerolipid metabolism, ABC transporters, amino sugar and nucleotide sugar metabolism and phosphotransferase system, were significantly down-regulated.
CONCLUSIONS
Based on the results, CovR plays positive regulative functions in the survivability and pathogenicity of S. suis 2 SC19 strain isolated from a pig.
Topics: Animals; Mice; Bacterial Proteins; Serogroup; Streptococcal Infections; Streptococcus suis; Swine; Swine Diseases; Virulence; Virulence Factors
PubMed: 37990198
DOI: 10.1186/s12917-023-03808-9 -
Proceedings of the National Academy of... Nov 2023The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can...
The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can affect the health of humans as well as livestock. Here, we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis of , a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography, and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages of emerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation of and acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential of is yet to be fully realized.
Topics: Animals; Humans; Swine; Streptococcal Infections; Farms; Swine Diseases; Virulence; Streptococcus suis; Livestock
PubMed: 37963246
DOI: 10.1073/pnas.2307773120 -
Animals : An Open Access Journal From... Oct 2023( HPS) is a prominent pathogenic bacterium in pig production. Its infection leads to widespread fibrinous inflammation in various pig tissues and organs, often in...
( HPS) is a prominent pathogenic bacterium in pig production. Its infection leads to widespread fibrinous inflammation in various pig tissues and organs, often in conjunction with various respiratory virus infections, and leads to substantial economic losses in the pig industry. Therefore, the rapid diagnosis of this pathogen is of utmost importance. In this study, we used recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR) technology to establish a convenient detection and analysis system for that is fast to detect, easy to implement, and accurate to analyze, known as RPA-CRISPR/Cas12a analysis. The process from sample to results can be completed within 1 h with high sensitivity (0.163 pg/μL of DNA template, < 0.05), which is 10 -fold higher than the common PCR method. The specificity test results show that the RPA-CRISPR/Cas12a analysis of did not react with other common pig pathogens, including type II and IX, , , , , and ( < 0.0001). The RPA-CRISPR/Cas12a assay was applied to 15 serotypes of clinical samples through crude extraction of nucleic acid by boiling method, and all of the samples were successfully identified. It greatly reduces the time and cost of nucleic acid extraction. Moreover, the method allows results to be visualized with blue light. The accurate and convenient detection method could be incorporated into a portable format as point-of-care (POC) diagnostics detection for at the field level.
PubMed: 37958075
DOI: 10.3390/ani13213317 -
Medicine Oct 2023Streptococcus suis (S suis)-associated infections are uncommon but life-threatening diseases. The clinical manifestations vary from general symptoms of bacterial...
RATIONALE
Streptococcus suis (S suis)-associated infections are uncommon but life-threatening diseases. The clinical manifestations vary from general symptoms of bacterial infection to fatal meningitis. The clinical manifestation and routine diagnostic testing is not specific enough to obtain well-time diagnosis.
PATIENT CONCERNS AND DIAGNOSIS
We report a case of meningitis and sepsis caused by S suis infection. A 70-year-old woman presented to our emergency department with generalized pain. After hospital admission, her condition rapidly deteriorated to fever, intracranial hypertension, and disturbance of consciousness. Examination of the blood and cerebrospinal fluid with metagenomic next-generation sequencing and bacterial cultures revealed S suis infection.
INTERVENTIONS AND OUTCOMES
After anti-infection therapy with meropenem and vancomycin, the patient recovered and was discharged from the hospital with no residual effects.
LESSONS
Human infections with S suis are extremely rare. If clinicians encounter a patient with fever, disturbance of consciousness, and intracranial hypertension, especially those who have been exposed to raw pork, S suis infection should be considered. Metagenomic next-generation sequencing can be a useful adjunct for the rapid diagnosis of S suis infection and aid in the planning of clinical treatment. Meanwhile, public health awareness is necessary to limit the risk of S suis infection.
Topics: Humans; Female; Aged; Streptococcus suis; Streptococcal Infections; Sepsis; Meningitis, Bacterial; Intracranial Hypertension
PubMed: 37904422
DOI: 10.1097/MD.0000000000035780