Prostaglandin E₂ (PGE₂), an essential endogenous lipid mediator for normal physiological functions, can also act as an inflammatory mediator in pathological conditions. We determined whether Staphylococcus aureus lipoproteins are essential for inducing PGE₂ secretion by immune cells and whether pattern recognition receptors mediate this process. PGE₂ levels secreted by mouse peritoneal macrophages infected with the S. aureus isogenic mutant, lgt::ermB (Δlgt; deficient in lipoprotein maturation), decreased compared with those from macrophages infected with wild-type (WT) S. aureus. Experiments using toll-like receptors 2 (TLR2)-deficient, TLR4-deficient, and NLRP3-deficient mice indicated that these 3 proteins are involved in macrophage PGE₂ secretion in response to S. aureus, and lipoproteins were essential for S. aureus invasion and survival within macrophages. Inhibition of endogenous PGE₂ synthesis had no effect on bacterial invasion. Exogenous PGE₂ inhibited phagocytosis in the WT S. aureus and its isogenic mutant but increased intracellular killing accompanied by enhanced IL-1β secretion. Our data demonstrate that S. aureus can induce macrophage TLR/mitogen-activated protein kinase/NF-κB signaling and that PGE₂ treatment upregulates NLRP3/caspase-1 signaling activation. Thus, macrophage PGE₂ secretion after S. aureus infection depends on bacterial lipoprotein maturation and macrophage receptors TLR2, TLR4, and NLRP3. Moreover, exogenous PGE₂ regulates S. aureus-induced macrophage activation through TLRs and NLRP3 inflammasome signaling.

Introduction: The unscientific and irrational use of antimicrobial drugs in dairy farms has led to the emergence of more serious drug resistance in Escherichia coli.Methods: In this study, cases of calf diarrhea in cattle farms around the Hohhot area were studied, and Escherichia coli were identified by PCR and biochemical methods, while the distribution of virulence and drug resistance genes of the isolates was analyzed.Results: The results showed that 21 strains of Escherichia coli were isolated from the diseased materials, and the isolation rate was 60%. The isolated strains belong to 15 ST types. The drug resistance levels of the isolated strains to 20 kinds of antimicrobial agent viz., penicillin, ampicillin, cefotaxime, cefepime, cefoxitin, and ceftriaxone were more than 50%. The resistance rate to meropenem was 10%. The resistance rates to tetracycline and doxycycline were 33% and 29%, to ciprofloxacin, levofloxacin and enrofloxacin were 48%, 33%, and 33%, to amikacin, kanamycin and gentamicin were 19%, 24% and 38%, to cotrimoxazole and erythromycin were 48% and 15%, to florfenicol, chloramphenicol and polymyxin B were 29%, 33%, and 5%. Nine strains of pathogenic calf diarrhea Escherichia coli were isolated by mouse pathogenicity test. The detection rates of virulence genes for the adhesion class were fimC (95%), IuxS (95%), eaeA (76%), fimA (62%), ompA (52%), and flu (24%). The detection rates for iron transporter protein like virulence genes were iroN (33%), iutA (19%), fyuA (14%), irp5 (9.5%), Iss (9.5%), and iucD (9.5%). The detection rates for toxin-like virulence genes were phoA (90%), Ecs3703 (57%), ropS (33%), hlyF (14%), and F17 (9.5%). The detection rates of tetracycline resistance genes in isolated strains were tetB (29%), tetA (19%) and tetD (14%). The detection rates for fluoroquinolone resistance genes were parC (Y305H, P333S, R355G) (9.5%), gyrA (S83L, D87N) (28%), qnrD (43%), and qnrS (9.5%). The detection rates for β-lactam resistance genes were bla_CTX–M (29%), bla_TEM (29%), and bla_SHV (9.5%). The detection rates for aminoglycoside resistance genes were strA-B (57%), aacC (33%), aac(3′)-IIa (29%), and aadAI (24%). The detection rates of chloramphenicol resistance genes floR and sulfa resistance genes sul2 were 24 and 33%.Conclusion: Pathogenic Escherichia coli causing diarrhea in calves contain abundant virulence genes and antibiotic resistance genes.

Endometritis is the most common bovine uterine disease following parturition. The role of prostaglandin E₂ (PGE₂) in the regulation of endometrial inflammation and repair is well understood. Excess PGE₂ is also generated in multiple inflammatory diseases, including endometritis. However, it remains unclear whether PGE₂ is associated with pathogen-induced inflammatory damage to the endometrium. To clarify the role of PGE₂ in pathogen-induced inflammatory damage, this study evaluated the production of PGE₂, inflammatory factors, and damage-associated molecular patterns (DAMPs) in cultured Escherichia coli-infected bovine endometrial tissue. PGE₂ production was significantly higher in E. coli-infected tissue, and in E. coli-infected tissue treated with 15-prostaglandin dehydrogenase (15-PGDH) inhibitors, as compared to uninfected tissue. Phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) were also upregulated in E. coli-infected tissue, while concentrations of arachidonic acid (AA), leukotrienes, DAMPs, and other proinflammatory factors increased. The accumulation of PGE₂ clearly damaged the cultured tissue. Treatment with the COX-2, mPGES-1, EP4, and protein kinase A (PKA) inhibitors decreased the production of PGE₂, inflammatory factors, and DAMPs, simultaneously alleviating the E. coli-induced endometrial tissue damage. Therefore, the PGE₂ that was generated by COX-2 and mPGES-1 accumulated, and this pathogenic PGE₂ increased inflammatory damage by upregulating inflammatory factors and DAMPs in E. coli-infected bovine endometrial tissue. This upregulation of inflammatory factors and DAMPs might be regulated by the EP₄-PKA signaling pathway.