Replication of Streptococcus equi subspecies zooepidemicus infection in swine.

Streptococcus equi subspecies zooepidemicus (SEZ) is a commensal bacterium of horses and causes infections in mammalian species, including humans. Historically, virulent strains of SEZ caused high mortality in pigs in China and Indonesia, while disease in the U.S. was infrequent. More recently, high mortality events in sows were attributed to SEZ in North America. The SEZ isolates from these mortality events have high genetic similarity to an isolate from an outbreak in China. Taken together, this may indicate SEZ is an emerging threat to swine health. To generate a disease model and evaluate the susceptibility of healthy, conventionally raised pigs to SEZ, we challenged sows and five-month-old pigs with an isolate from a 2019 mortality event. Pigs were challenged with a genetically similar guinea pig isolate or genetically distinct horse isolate to evaluate comparative virulence. The swine isolate caused severe systemic disease in challenged pigs with 100 % mortality. Disease manifestation in sows was similar to field reports: lethargy/depression, fever, reluctance to rise, and high mortality. The guinea pig isolate also caused severe systemic disease; however, most five-month-old pigs recovered. In contrast, the horse isolate did not cause disease and was readily cleared from the respiratory tract. In conclusion, we were able to replicate disease reported in the field. The results indicate differences in virulence between isolates, with the highest virulence associated with the swine isolate. Additionally, we generated a challenge model that can be used in future research to evaluate virulence factors and disease prevention strategies.

Piglet innate immune response to Streptococcus suis colonization is modulated by the virulence of the strain.

Streptococcus suis is a zoonotic pathogen of swine involved in arthritis, polyserositis, and meningitis. Colonization of piglets by S. suis is very common and occurs early in life. The clinical outcome of infection is influenced by the virulence of the S. suis strains and the immunity of the animals. Here, the role of innate immunity was studied in cesarean-derived colostrum-deprived piglets inoculated intranasally with either virulent S. suis strain 10 (S10) or non-virulent S. suis strain T15. Colonization of the inoculated piglets was confirmed at the end of the study by PCR and immunohistochemistry. Fever (≥40.5 °C) was more prevalent in piglets inoculated with S10 compared to T15 at 4 h after inoculation. During the 3 days of monitoring, no other major clinical signs were detected. Accordingly, only small changes in transcription of genes associated with the antibacterial innate immune response were observed at systemic sites, with S10 inducing an earlier response than T15 in blood. Local inflammatory response to the inoculation, evaluated by transcriptional analysis of selected genes in nasal swabs, was more sustained in piglets inoculated with the virulent S10, as demonstrated by transcription of inflammation-related genes, such as IL1B, IL1A, and IRF7. In contrast, most of the gene expression changes in trachea, lungs, and associated lymph nodes were observed in response to the non-virulent T15 strain. Thus, S. suis colonization in the absence of systemic infection induces an innate immune response in piglets that appears to be related to the virulence potential of the colonizing strain.

The Indirect Impact of the SARS-CoV-2 Pandemic on Invasive Group a Streptococcus, Streptococcus Pneumoniae and Staphylococcus Aureus Infections in Houston Area Children.

Masking and social distancing have been adopted to mitigate the severe acute respiratory syndrome coronavirus 2 pandemic. We evaluated the indirect impact of severe acute respiratory syndrome coronavirus 2 prevention strategies on invasive Staphylococcus aureus, Streptococcus pneumoniae (pneumococcus) and Group A Streptococcus in Houston area children. We observed a decline in invasive pneumococcal disease and invasive Group A Streptococcus temporally associated with social distancing/masking/school closures.

Genome-Wide fitness analysis of group B Streptococcus in human amniotic fluid reveals a transcription factor that controls multiple virulence traits.

Streptococcus agalactiae (group B Streptococcus; GBS) remains a dominant cause of serious neonatal infections. One aspect of GBS that renders it particularly virulent during the perinatal period is its ability to invade the chorioamniotic membranes and persist in amniotic fluid, which is nutritionally deplete and rich in fetal immunologic factors such as antimicrobial peptides. We used next-generation sequencing of transposon-genome junctions (Tn-seq) to identify five GBS genes that promote survival in the presence of human amniotic fluid. We confirmed our Tn-seq findings using a novel CRISPR inhibition (CRISPRi) gene expression knockdown system. This analysis showed that one gene, which encodes a GntR-class transcription factor that we named MrvR, conferred a significant fitness benefit to GBS in amniotic fluid. We generated an isogenic targeted deletion of the mrvR gene, which had a growth defect in amniotic fluid relative to the wild type parent strain. The mrvR deletion strain also showed a significant biofilm defect in vitro. Subsequent in vivo studies showed that while the mutant was able to cause persistent murine vaginal colonization, pregnant mice colonized with the mrvR deletion strain did not develop preterm labor despite consistent GBS invasion of the uterus and the fetoplacental units. In contrast, pregnant mice colonized with wild type GBS consistently deliver prematurely. In a sepsis model the mrvR deletion strain showed significantly decreased lethality. In order to better understand the mechanism by which this newly identified transcription factor controls GBS virulence, we performed RNA-seq on wild type and mrvR deletion GBS strains, which revealed that the transcription factor affects expression of a wide range of genes across the GBS chromosome. Nucleotide biosynthesis and salvage pathways were highly represented among the set of differentially expressed genes, suggesting that MrvR may be involved in regulating nucleotide availability.

Pol-miR-150 regulates anti-bacterial and viral infection in Japanese flounder (Paralichthys olivaceus) via the lysosomal protein LMP2L.

MiR-150 is a microRNA (miRNA) present in a number of teleost species, but its target and regulation mechanism are unknown. Similarly, lysosome membrane protein 2-like (LMP2L) is a gene identified in fish but with unknown function. In this study, we examined the regulation mechanism and function of flounder miR-150 (named pol-miR-150) and its target gene LMP2L (named PoLMP2L) in association with bacterial and viral infection. We found that pol-miR-150 expression was not only modulated by the bacterial pathogen Streptococcus iniae but also by the viral pathogen megalocytivirus. Pol-miR-150 targeted PoLMP2L by binding to the 3'-untranslated region (3'-UTR) of PoLMP2L and inhibited PoLMP2L expression in vitro and in vivo. PoLMP2L is a member of the CD36 superfamily of scavenger receptors and homologous to but phylogenetically distinct from lysosomal integral membrane protein type 2 (LIMP2). PoLMP2L was localized mainly in the lysosomes and expressed in multiple organs of flounder. In vivo knockdown and overexpression of PoLMP2L enhanced and suppressed, respectively, S. iniae dissemination in flounder tissues, whereas in vivo knockdown and overexpression of pol-miR-150 produced the opposite effects on S. iniae dissemination. In addition, pol-miR-150 knockdown also significantly inhibited the replication of megalocytivirus. The results of this study revealed the regulation mechanism and immune functions of fish miR-150 and LMP2L, and indicated that LMP2L and miR-150 play an important role in the antimicrobial immunity of fish.

The otc gene of Streptococcus suis plays an important role in biofilm formation, adhesion, and virulence in a murine model.

Streptococcus suis (S. suis) is an emerging zoonotic pathogen that can cause meningitis, arthritis, pneumonia, and sepsis. It poses a serious threat to the swine industry and public health worldwide. Ornithine carbamoyltransferase (OTC) is involved in the arginine deiminase system. OTC, which is a widely distributed enzyme in microorganisms, mammals, and higher plants, catalyzes the conversion of ornithine to citrulline. The present study showed that the otc gene plays an important role in the pathogenesis of S. suis infections. The ability of an otc-deficient mutant (Δotc) to form a biofilm was significantly reduced compared to the wild-type (WT) strain, as determined by crystal violet staining. Confocal laser scanning microscopy and scanning electron microscopy observations showed that the weakening of biofilm formation by the Δotc strain is related to a decrease in the extracellular matrix. In addition, compared to the WT strain, the Δotc strain had a reduced capacity to adhere to human laryngeal epidermoid carcinoma (HEp-2) cells compared to the WT strain. A real-time PCR analysis showed that the expression of adhesion-related genes by the Δotc strain was also lower than that of the WT strain. The virulence of the Δotc strain was significantly lower than that of the WT strain in a murine infection model. In addition, a histological analysis showed that the pathogenicity of the Δotc strain was lower than that of the WT strain, causing only slight inflammatory lesions in lung, liver, spleen, and kidney tissues. No significant differences were observed between the complemented mutant (CΔotc) and WT strains with respect to biofilm formation, adhesion, gene expression, and virulence. The present study provided evidence that the otc gene plays a pivotal role in the regulation of S. suis adhesion and biofilm formation. It also suggested that the otc gene is indirectly involved in the pathogenesis of S. suis serotype 2 infections.

Comparative study of Revogene GBS LB assay and GeneXpert GBS LB assay for the detection of group B Streptococcus in prenatal screening samples.

BACKGROUND: Group B Streptococcal (GBS) infections in the United States are a leading cause of meningitis and sepsis in newborns. The CDC therefore recommends GBS screening for all pregnant women at 35-37 weeks of gestation and administration of intrapartum prophylaxis (in those that tested positive) as an effective means of controlling disease transmission. Several FDA approved molecular diagnostic tests are available for rapid and accurate detection of GBS in antepartum women. METHOD: In this study, we report a clinical comparison of the Xpert GBS LB assay and a novel FDA-cleared test, Revogene GBS LB assay. A total of 250 vaginal-rectal swabs from women undergoing prenatal screening were submitted to the University of Wisconsin's clinical microbiology laboratory for GBS testing. RESULTS: We found 96.8% of samples were concordant between the two tests, while 3.2% were discordant with a positive percent agreement of 98.0% and a negative percent agreement of 96.5% between the Revogene GBS LB assay and the GeneXpert GBS LB assay. CONCLUSION: Overall, we report that both assays perform well for the detection of GBS colonization in pregnant women.

Characterization of Streptococcus iniae-induced microRNA profiles in Paralichthys olivaceus and identification of pol-3p-10740_175 as a regulator of antibacterial immune response.

MicroRNAs (miRNAs) are involved in many biological activities including immune defense against pathogens. In this study, we applied high-throughput sequencing technology to examine miRNAs in Japanese flounder (Paralichthys olivaceus) infected with Streptococcus iniae at different times. A total of 1038 miRNAs were identified, of which, 249 were novel miRNAs, and 81 showed differential expression (named DEmiRNAs) after S. iniae infection. Of the 81 DEmiRNAs identified, 34 and 58 occurred at 6 h and 24 h post-infection, respectively; most DEmiRNAs were strongly time-specific, and only 13.6% of the DEmiRNAs were shared between the two time points. A total of 9582 target genes were predicted for the 81 DEmiRNAs. The putative target genes were enriched in various GO and KEGG pathways of biological processes and molecular/cellular functions, in particular endocytosis, regulation of transcription, lysososme, and the signaling pathways of MAPK, ErbB, and AMPK. One of the DEmiRNAs, pol-3p-10740_175, was found to target dual specificity phosphatase 6 (Dusp6) and repress the expression of the latter. Transfection of flounder FG cells with pol-3p-10740_175 caused a significant inhibition on S. iniae invasion. The results of this study provided the first S. iniae-induced miRNA profile in Japanese flounder and indicated that flounder miRNAs play an important role in antibacterial immunity.

Examination of Australian Streptococcus suis isolates from clinically affected pigs in a global context and the genomic characterisation of ST1 as a predictor of virulence.

Streptococcus suis is a major zoonotic pathogen that causes severe disease in both humans and pigs. Australia's pig herd has been quarantined for over 30 years, however S. suis remains a significant cause of disease. In this study, we investigated S. suis from 148 cases of clinical disease in pigs from 46 pig herds over a period of seven years, to determine the level of genetic difference from international isolates that may have arisen over the 30 years of separation. Isolates underwent whole genome sequencing, genome analysis and antimicrobial susceptibility testing. Data was compared at the core genome level to clinical isolates from overseas. Results demonstrated five predominant multi-locus sequence types and two major cps gene types (cps2 and 3). At the core genome level Australian isolates clustered predominantly within one large clade consisting of isolates from the UK, Canada and North America. A small proportion of Australian swine isolates (5%) were phylogenetically associated with south-east Asian and UK isolates, many of which were classified as causing systemic disease, and derived from cases of human and swine disease. Based on this dataset we provide a comprehensive outline of the current S. suis clones associated with disease in Australian pigs and their global context, with the main finding being that, despite three decades of separation, Australian S. suis are genomically similar to overseas strains. In addition, we show that ST1 clones carry a constellation of putative virulence genes not present in other Australian STs.

Pathogenic mechanisms of invasive group A Streptococcus infections by influenza virus-group A Streptococcus superinfection.

Group A Streptococcus (GAS) are pathogenic bacteria of the genus Streptococcus and cause severe invasive infections that comprise a wide range of diverse diseases, including acute respiratory distress syndrome, renal failure, toxic shock-like syndrome, sepsis, cellulitis and necrotizing fasciitis. The essential virulence, infected host and external environmental factors required for invasive GAS infections have not yet been determined. Superinfection with influenza virus and GAS induced invasive GAS infections was demonstrated by our team in a mouse model, after which clinical cases of invasive GAS infections secondary to influenza virus infection were reported by other investigators in Japan, USA, Canada, UK China, and other countries. However, the pathogenic mechanisms underlying influenza virus-GAS superinfection are not yet fully understood. The present review describes the current knowledge about invasive GAS infections by superinfection. Topics addressed include the bacteriological, virological and immunological mechanisms impacting invasion upon superinfection on top of underlying influenza virus infection by GAS and other bacteria (i.e., Streptococcus pneumoniae and Staphylococcus aureus). Future prospects are also discussed.

Protective responses of two paralogs of granulocyte colony stimulating factor (GCSF) in rock bream, Oplegnathus fasciatus during bacterial and viral infection.

Granulocyte colony stimulating factor (GCSF) has a key role in the production of neutrophilic granulocytes during normal hematopoietic development and release of neutrophils into the blood circulation. In this study we have identified and characterized two paralogs of GCSF (RbGCSF) in rock bream. Although RbGCSF-1 and RbGCSF-2 share low sequence conservation, its domains and protein structure still share significant similarity. Basal levels of RbGCSF-1 gene expression was high in peripheral blood leukocytes (PBLs), spleen and intestine whereas the RbGCSF-2 was highly expressed in PBLs and kidney, of healthy animals. A significant induction of RbGCSFs were observed after the challenge with Streptococcus iniae in kidney, spleen and gills during initial hours of infection. Whereas Edwarsiella tarda infection caused a reasonable expression in kidney. Red seabream iridovirus caused induction of RbGCSF-1 transcription only in gills during initial hours. This higher expression of RbGCSF in early hours may be its response to induce emergency hematopoiesis, due to shortage of neutrophils to combat the surge in pathogens. The difference in induction of RbGCSF paralogs during infection may constitute to its different roles or overlapping functions.

[Cerebrospinal fluid shunt malfunction not associated with ventricular enlargement. A case report and literature review]. / Disfunktsiya shunta tserebrospinal'noi zhidkosti bez rasshireniya zheludochkov mozga. Sluchai iz praktiki i obzor literatury.

Substantiation of the shunt failure diagnosis and subsequent consideration of indications for surgical elimination of the malfunction is a laborious and challenging process. Identification of a malfunction in doubtful cases requires, in addition to standard examinations, extra diagnostic procedures, which may delay making a decision for several weeks to several months. The article describes a case of mechanical CSF shunt malfunction (breakage and failure of a peritoneal catheter in a 7-year-old girl) with intracranial hypertension symptoms, but without typical enlargement of the brain ventricles. According to the medical history, congenital hydrocephalus in the child was accompanied by an inflammatory process of bacterial and viral etiology. The absence of brain ventricle enlargement was shown not to exclude a probability of shunt malfunction. In this case, a specific phenomenon, an intraparenchymatous cerebrospinal fluid "lake" surrounding a ventricular catheter, was observed. Shunting recovery did not lead to a significant reduction in the phenomenon size. Causes underlying this phenomenon require further investigation.

Genetic Diversity among Group A Streptococcus Isolated from Throats of Healthy and Symptomatic Children.

BACKGROUND: Group A streptococcus (GAS) is the commonest bacterial cause of pharyngitis. Children in the age group of 5-15 years are most commonly affected. It can also colonize throats of healthy children in this age group. Both cases and carriers can transmit it in the community. METHODS: Throat swab samples were collected from 1849 asymptomatic and 371 symptomatic children. RESULTS: The rate of isolation of GAS was 1.41% among the asymptomatic group and 7.55% among the symptomatic group. Nine different emm types were encountered in the asymptomatic children and 14 among the symptomatic children. CONCLUSION: Throat swab cultures must be used in all cases of pharyngitis. Early and appropriate antibiotic therapy will prevent complications. Asymptomatic throat carriage of GAS in children was low in our study. However, they can still act as reservoirs. Emm typing helps in understanding epidemiology and finding new types.

Emergence of a novel lineage containing a prophage in emm/M3 group A Streptococcus associated with upsurge in invasive disease in the UK.

A sudden increase in invasive Group A Streptococcus (iGAS) infections associated with emm/M3 isolates during the winter of 2008/09 prompted the initiation of enhanced surveillance in England. In order to characterise the population of emm/M3 GAS within the UK and determine bacterial factors that might be responsible for this upsurge, 442 emm/M3 isolates from cases of invasive and non-invasive infections during the period 2001-2013 were subjected to whole genome sequencing. MLST analysis differentiated emm/M3 isolates into three sequence types (STs): ST15, ST315 and ST406. Analysis of the whole genome SNP-based phylogeny showed that the majority of isolates from the 2008-2009 upsurge period belonged to a distinct lineage characterized by the presence of a prophage carrying the speC exotoxin and spd1 DNAase genes but loss of two other prophages considered typical of the emm/M3 lineage. This lineage was significantly associated with the upsurge in iGAS cases and we postulate that the upsurge could be attributed in part to expansion of this novel prophage-containing lineage within the population. The study underlines the importance of prompt genomic analysis of changes in the GAS population, providing an advanced public health warning system for newly emergent, pathogenic strains.

Isquemia mesentérica masiva en paciente puerperal por shock tóxico estreptocócico / Massive mesenteric ischemia in a puerperal woman due to streptococcal toxic shock

El estreptococo B hemolítico del grupo A es una bacteria aerobia Gram +, que puede producir una gran variedad de síndromes infecciosos en el puerperio. Hasta un tercio de las infecciones se complicará con un shock tóxico estafilocócico, caracterizado por shock y disfunción multiorgánica. Cultivos, diagnóstico y tratamiento precoces son vitales para el buen pronóstico. Presentamos el caso de una paciente puerperal con un síndrome de shock tóxico estreptocócico, complicado con una isquemia mesentérica masiva, donde tratamiento antibiótico y cirugía precoz fueron claves para la evolución

B hemolytic group A streptococcus is an aerobic Gram-positive bacteria that can produce a wide variety of infectious syndromes in the puerperium. Up to one-third of infections will be complicated by streptococcal toxic shock, characterized by shock and multiorgan dysfunction. Early cultures, diagnosis and treatment are vital to good prognosis. We present the case of a puerperal patient with streptococcal toxic shock, complicated by massive mesenteric ischemia, in whom antibiotic treatment and early surgery were the key to outcome

Impact of an experimental PRRSV and Streptococcus suis coinfection on the pharmacokinetics of ceftiofur hydrochloride after intramuscular injection in pigs.

This study determined the impact of porcine reproductive and respiratory syndrome virus (PRRSV) and Streptococcus suis coinfection on the pharmacokinetic (PK) profile of ceftiofur hydrochloride in pigs after intramuscular (i.m.) injection. Eighteen clinically normal crossbred gilts were assigned by weight into a challenge group (10 pigs) and control group (eight pigs). Pigs in both groups received a single i.m. injection of ceftiofur hydrochloride (Excenel RTU Sterile Suspension; Zoetis) at a 5 mg/kg BW dose. Serial blood samples were collected to characterize the plasma concentration curve. After a 10 days drug washout period, the challenge group was inoculated with 2 mL of PRRSV isolate VR-2385 (10(5.75) 50% tissue culture infective doses per mL) intranasally and 8 days later inoculated S. suis. When clinical disease was evident, the second PK assessment began in both challenge and control groups. Coinfected pigs demonstrated lower values of AUC and CMAX , but higher values of Cl/F and Vz/F indicating drug kinetics were altered by infection. The data from this study have implications on ceftiofur treatment regimens in diseased pigs.

Increased production of suilysin contributes to invasive infection of the Streptococcus suis strain 05ZYH33.

Streptococcus suis serotype 2 (SS2) is widely recognized in the veterinary world as the cause of rapidly progressive and fatal sepsis in infant pigs, manifested with meningitis, polyarthritis and pneumonia. It has evolved into a highly infectious strain, and caused two large-scale outbreaks of human epidemic in China, characterized bytypical toxic-shock syndrome and invasive infection. However, the molecular basis of virulence of this emerging zoonotic pathogen is still largely unknown. The present study shows that the sequence type (ST)7 epidemic strain S. suis 05ZYH33 causes higher mortality, higher necrosis of polymorphonuclear neutrophils and a significantly higher damage to human umbilical vein endothelial cells compared to the non-epidemic strain S. suis 1940. These differences appear to associate with the enhanced secretion of suilysin (sly) by S. suis 05ZYH33 compared to the non-epidemic strain 1940. Inclusion of additional strains confirmed that the epidemic ST7 strains produce more sly protein (mean, 1.49 g/ml; range, 0.76­1.91 g/ml) than non­epidemic strains (mean, 0.33 g/ml; range, 0.07-0.94 g/ml), and this difference is significant (P<0.001). The nonpolar mutant strain S. suis Δsly, constructed from the epidemic ST7 strain S. suis 05ZYH33 confirmed the role of sly on the enhanced virulence of S. suis ST7 strains. These findings suggest that increased sly production in S. suis 05ZYH33 facilitates penetration to the epithelium and its survival in the bloodstream, thereby contributing to the invasive infection.

The classical lancefield antigen of group a Streptococcus is a virulence determinant with implications for vaccine design.

Group A Streptococcus (GAS) is a leading cause of infection-related mortality in humans. All GAS serotypes express the Lancefield group A carbohydrate (GAC), comprising a polyrhamnose backbone with an immunodominant N-acetylglucosamine (GlcNAc) side chain, which is the basis of rapid diagnostic tests. No biological function has been attributed to this conserved antigen. Here we identify and characterize the GAC biosynthesis genes, gacA through gacL. An isogenic mutant of the glycosyltransferase gacI, which is defective for GlcNAc side-chain addition, is attenuated for virulence in two infection models, in association with increased sensitivity to neutrophil killing, platelet-derived antimicrobials in serum, and the cathelicidin antimicrobial peptide LL-37. Antibodies to GAC lacking the GlcNAc side chain and containing only polyrhamnose promoted opsonophagocytic killing of multiple GAS serotypes and protected against systemic GAS challenge after passive immunization. Thus, the Lancefield antigen plays a functional role in GAS pathogenesis, and a deeper understanding of this unique polysaccharide has implications for vaccine development.

The ß-domain of cluster 2b streptokinase is a major determinant for the regulation of its plasminogen activation activity by cellular plasminogen receptors.

Cluster 2b streptokinase (SK2b), secreted by invasive skin-trophic strains of Streptococcus pyogenes (GAS), is a human plasminogen (hPg) activator that optimally functions when human plasma hPg is bound, via its kringle-2 domain, to cognizant bacterial cells through the a1a2 domain of the major cellular hPg receptor, Plasminogen-binding group A streptococcal M-like protein (PAM). Another class of streptokinases (SK1), secreted primarily by GAS strains that possess affinity for pharyngeal infections, does not require PAM-bound hPg for optimal activity. We find herein that replacement of the central ß-domain of SK2b with the same module from SK1 reduces the dependency of SK2b on PAM, and the converse is true when the ß-domain of SK1 is replaced with this same region of SK2b. These data suggest that simple evolutionary shuttling of protein domains in GAS can be employed by GAS to rapidly generate strains that differ in tissue tropism and invasive capability and allow the bacteria to survive different challenges by the host.

Pig α1-acid glycoprotein: characterization and first description in any species as a negative acute phase protein.

The serum protein α1-acid glycoprotein (AGP), also known as orosomucoid, is generally described as an archetypical positive acute phase protein. Here, porcine AGP was identified, purified and characterized from pooled pig serum. It was found to circulate as a single chain glycoprotein having an apparent molecular weight of 43 kDa by SDS-PAGE under reducing conditions, of which approximately 17 kDa were accounted for by N-bound oligosaccharides. Those data correspond well with the properties of the protein predicted from the single porcine AGP gene (ORM1, Q29014 (UniProt)), containing 5 putative glycosylation sites. A monoclonal antibody (MAb) was produced and shown to quantitatively and specifically react with all microheterogenous forms of pig AGP as analyzed by 2-D electrophoresis. This MAb was used to develop an immunoassay (ELISA) for quantification of AGP in pig serum samples. The adult serum concentrations of pig AGP were in the range of 1-3 mg/ml in a number of conventional pig breeds while it was lower in Göttingen and Ossabaw minipigs (in the 0.3 to 0.6 mg/ml range) and higher in young (2-5 days old) conventional pigs (mean: 6.6 mg/ml). Surprisingly, pig AGP was found to behave as a negative acute phase protein during a range of experimental infections and aseptic inflammation with significant decreases in serum concentration and in hepatic ORM1 expression during the acute phase response. To our knowledge this is the first description in any species of AGP being a negative acute phase protein.