Interplay between group A Streptococcus and host innate immune responses.

SUMMARYGroup A Streptococcus (GAS), also known as Streptococcus pyogenes, is a clinically well-adapted human pathogen that harbors rich virulence determinants contributing to a broad spectrum of diseases. GAS is capable of invading epithelial, endothelial, and professional phagocytic cells while evading host innate immune responses, including phagocytosis, selective autophagy, light chain 3-associated phagocytosis, and inflammation. However, without a more complete understanding of the different ways invasive GAS infections develop, it is difficult to appreciate how GAS survives and multiplies in host cells that have interactive immune networks. This review article attempts to provide an overview of the behaviors and mechanisms that allow pathogenic GAS to invade cells, along with the strategies that host cells practice to constrain GAS infection. We highlight the counteractions taken by GAS to apply virulence factors such as streptolysin O, nicotinamide-adenine dinucleotidase, and streptococcal pyrogenic exotoxin B as a hindrance to host innate immune responses.

Group A Streptococcus interactions with the host across time and space.

Group A Streptococcus (GAS) has a fantastically wide tissue tropism in humans, manifesting as different diseases depending on the strain's virulence factor repertoire and the tissue involved. Activation of immune cells and pro-inflammatory signaling has historically been considered an exclusively host-protective response that a pathogen would seek to avoid. However, recent advances in human and animal models suggest that in some tissues, GAS will activate and manipulate specific pro-inflammatory pathways to promote growth, nutrient acquisition, persistence, recurrent infection, competition with other microbial species, dissemination, and transmission. This review discusses molecular interactions between the host and pathogen to summarize how infection varies across tissue and stages of inflammation. A need for inflammation for GAS survival during common, mild infections may drive selection for mechanisms that cause pathological and excess inflammation severe diseases such as toxic shock syndrome, necrotizing fasciitis, and rheumatic heart disease.

Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice.

Streptococcus anginosus (S. anginosus) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice. In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (ANXA2) receptor on gastric epithelial cells. Interaction of TMPC with ANXA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. ANXA2 knockout abrogated the induction of MAPK by S. anginosus. Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.

Bovine neutrophils stimulated with Streptococcus uberis induce neutrophil extracellular traps, and cause cytotoxicity and transcriptional upregulation of inflammatory cytokine genes in bovine mammary epithelial cells.

This study aimed to understand the response of neutrophils stimulated by Streptococcus uberis, a major cause of mastitis. It was found that the production of neutrophil extracellular traps (NETs) was induced in milk clots from mastitic milk produced by S. uberis-infected bovine udders. The release of NETs from neutrophils stimulated by S. uberis was investigated. Bovine neutrophils cocultured with S. uberis in vitro released the components of NETs, which contained extracellular DNA and elastase. Bovine mammary epithelial cells (BMECs) incubated in coculture supernatants containing components of NETs, caused cytotoxicity and transcriptional upregulation of inflammatory cytokines, including of interleukin (IL) -1ß, tumor necrosis factor (TNF)-α, IL-6, and IL-8, in BMECs. These findings suggest that bovine neutrophils stimulated by S. uberis induce responses that cause exacerbated inflammation, such as NET formation, cytotoxicity against BMECs, and increased production of inflammatory cytokines. Bovine neutrophil responses stimulated by S. uberis could be involved in the progression of S. uberis-induced mastitis.

Skin IL-17A and IFN-γ Production Correlate with Disease Severity in Patients with Psoriasis and Streptococcal Infection.

Psoriasis is a multisystemic inflammatory disorder mainly involving the skin and joints, whose etiopathogenesis is still not completely understood. An association with streptococcal throat infection has been suggested. We aim to investigate a correlation between IL-17A and IFN-γ production by T cells infiltrating skin lesions and PASI in 313 patients with psoriasis, compared with that in 252 healthy controls. The phenotype of ß-hemolytic Streptococci-specific infiltrating T cells in skin lesions was evaluated and characterized for IFN-γ, IL-4, and IL-17A production. In addition, PBMCs were tested by ELISpot for IFN-γ and IL-17A after streptococcal antigen exposure. A total of 64 of 313 (20.4%) patients with psoriasis had throat streptococcal infection. Of the 3,868 skin-derived T-cell clones from psoriasis with streptococcal infection, 66% proliferated in response to ß-hemolytic Streptococci antigens. Most ß-hemolytic Streptococci-specific T cells displayed T helper 17 and T helper 1 phenotypes. The levels of IFN-γ and IL-17A secreted by skin-infiltrating T cells of patients with psoriasis significantly correlated with PASI score. In ß-hemolytic Streptococci-positive patients, IFN-γ and IL-17A production by peripheral blood T cells after stimulation with streptococcal antigens was quantified by ELISpot. The results obtained may suggest ELISpot as a useful diagnostic tool to identify patients with psoriasis that may deserve antibiotic treatment.

Vimentin affects inflammation and neutrophil recruitment in airway epithelium during Streptococcus suis serotype 2 infection.

Streptococcus suis serotype 2 (SS2) frequently colonizes the swine upper respiratory tract and can cause Streptococcal disease in swine with clinical manifestations of pneumonia, meningitis, and septicemia. Previously, we have shown that vimentin, a kind of intermediate filament protein, is involved in the penetration of SS2 through the tracheal epithelial barrier. The initiation of invasive disease is closely related to SS2-induced excessive local inflammation; however, the role of vimentin in airway epithelial inflammation remains unclear. Here, we show that vimentin deficient mice exhibit attenuated lung injury, diminished production of proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and the IL-8 homolog, keratinocyte-derived chemokine (KC), and substantially reduced neutrophils in the lungs following intranasal infection with SS2. We also found that swine tracheal epithelial cells (STEC) without vimentin show decreased transcription of IL-6, TNF-α, and IL-8. SS2 infection caused reassembly of vimentin in STEC, and pharmacological disruption of vimentin filaments prevented the transcription of those proinflammatory cytokines. Furthermore, deficiency of vimentin failed to increase the transcription of nucleotide oligomerization domain protein 2 (NOD2), which is known to interact with vimentin, and the phosphorylation of NF-κB protein p65. This study provides insights into how vimentin promotes excessive airway inflammation, thereby exacerbating airway injury and SS2-induced systemic infection.

Infection-Related Glomerulonephritis in Children and Adults.

Infection-related glomerulonephritis is an immunologically mediated glomerular injury after an infection. Glomerulonephritis may occur with the infection or after a variable latent period. Poststreptococcal glomerulonephritis (PSGN) is the prototype of infection-related glomerulonephritis. The streptococcal antigens, nephritis-associated plasmin-like receptor and streptococcal exotoxin B, have emerged as major players in the pathogenesis of PSGN. Although PSGN is the most common infection-related glomerulonephritis in children, in adults, glomerulonephritis is secondary to bacteria such as staphylococci, viruses such as hepatitis C, and human immunodeficiency virus, and, rarely, parasitic infections. Supportive therapy is the mainstay of treatment in most infection-related glomerulonephritis. Treatment of the underlying infection with specific antibiotics and antiviral medications is indicated in some infections. Parasitic infections, although rare, may be associated with significant morbidity. Poststreptococcal glomerulonephritis is a self-limiting condition with a good prognosis. However, bacterial, viral, and parasitic infections may be associated with significant morbidity and long-term consequences. Epidemiologic studies are required to assess the global burden of infection-related glomerulonephritis. A better understanding of the pathogenesis of infection-related glomerulonephritis may unravel more treatment options and preventive strategies.

Spatial profiling of the placental chorioamniotic membranes reveals upregulation of immune checkpoint proteins during Group B Streptococcus infection in a nonhuman primate model.

Background: Preterm birth is a leading cause of neonatal mortality, which is often complicated by intrauterine infection and inflammation. We have established a nonhuman primate model of Group B Streptococcus (GBS, Streptococcus agalactiae) infection-associated preterm birth. Immune checkpoints are modulators of the immune response by activating or suppressing leukocyte function and are understudied in preterm birth. The objective of this study was to spatially profile changes in immune protein expression at the maternal-fetal interface during a GBS infection with a focus on immune checkpoints. Methods: Twelve nonhuman primates (pigtail macaques, Macaca nemestrina) received a choriodecidual inoculation of either: 1) 1-5 X 108 colony forming units (CFU) of hyperhemolytic/hypervirulent GBS (GBSΔcovR, N=4); 2) an isogenic/nonpigmented strain (GBS ΔcovRΔcylE, N=4); or, 3) saline (N=4). A Cesarean section was performed at preterm labor or 3 days after GBS infection or 7 days after saline inoculation. Nanostring GeoMx® Digital Spatial Profiling technology was used to segment protein expression within the amnion, chorion, and maternal decidua at the inoculation site using an immuno-oncology panel targeting 56 immunoproteins enriched in stimulatory and inhibitory immune checkpoint proteins or their protein ligands. Statistical analysis included R studio, Kruskal-Wallis, Pearson and Spearman tests. Results: Both inhibitory and stimulatory immune checkpoint proteins were significantly upregulated within the chorioamniotic membranes and decidua (VISTA, LAG3, PD-1, CD40, GITR), as well as their ligands (PD-L1, PD-L2, CD40L; all p<0.05). Immunostaining for VISTA revealed positive (VISTA+) cells, predominantly in the chorion and decidua. There were strong correlations between VISTA and amniotic fluid concentrations of IL-1ß, IL-6, IL-8, and TNF-α (all p<0.05), as well as maternal placental histopathology scores (p<0.05). Conclusion: Differential regulation of multiple immune checkpoint proteins in the decidua at the site of a GBS infection indicates a major perturbation in immunologic homeostasis that could benefit the host by restricting immune-driven pathologies or the pathogen by limiting immune surveillance. Protein expression of VISTA, an inhibitory immune checkpoint, was upregulated in the chorion and decidua after GBS infection. Investigating the impact of innate immune cell expression of inhibitory immune checkpoints may reveal new insights into placental host-pathogen interactions at the maternal-fetal interface.

Group B Streptococcus Surface Protein ß: Structural Characterization of a Complement Factor H-Binding Motif and Its Contribution to Immune Evasion.

The ß protein from group B Streptococcus (GBS) is a ∼132-kDa, cell-surface exposed molecule that binds to multiple host-derived ligands, including complement factor H (FH). Many details regarding this interaction and its significance to immune evasion by GBS remain unclear. In this study, we identified a three-helix bundle domain within the C-terminal half of the B75KN region of ß as the major FH-binding determinant and determined its crystal structure at 2.5 Å resolution. Analysis of this structure suggested a role in FH binding for a loop region connecting helices α1 and α2, which we confirmed by mutagenesis and direct binding studies. Using a combination of protein cross-linking and mass spectrometry, we observed that B75KN bound to complement control protein (CCP)3 and CCP4 domains of FH. Although this binding site lies within a complement regulatory region of FH, we determined that FH bound by ß retained its decay acceleration and cofactor activities. Heterologous expression of ß by Lactococcus lactis resulted in recruitment of FH to the bacterial surface and a significant reduction of C3b deposition following exposure to human serum. Surprisingly, we found that FH binding by ß was not required for bacterial resistance to phagocytosis by neutrophils or killing of bacteria by whole human blood. However, loss of the B75KN region significantly diminished bacterial survival in both assays. Although our results show that FH recruited to the bacterial surface through a high-affinity interaction maintains key complement-regulatory functions, they raise questions about the importance of FH binding to immune evasion by GBS as a whole.

A case of acute poststreptococcal glomerulonephritis complicated by interstitial nephritis related to streptococcal pyrogenic exotoxin B.

This paper presents the case of a patient who developed acute kidney injury and nephrotic syndrome following streptococcal cutaneous infection. He presented with microhematuria, severe proteinuria and systemic edema 5 days after infection. Blood examination showed elevated creatinine level, hypocomplementemia, and elevated anti-streptolysin O level. Renal biopsy revealed endocapillary proliferative glomerulonephritis with tubulointerstitial nephritis (TIN). Immunofluorescence revealed C3-dominant glomerular staining, while electron microscopy showed hump-shaped subepithelial deposits. The patient was therefore diagnosed with poststreptococcal glomerulonephritis. The unique histological feature was C3 deposition in the tubular basement membrane (TBM), in which we detected streptococcal pyrogenic exotoxin B (SpeB), a nephritogenic antigen produced by streptococci. No nephritis-associated plasmin receptor or plasmin activity was evident in the TBM. These nephritogenic antigens and upregulation of plasmin activity were observed in glomeruli. This case suggests that TIN after poststreptococcal infection might be partially attributable to SpeB toxicity.

Host-to-Host Group A Streptococcus Transmission Causes Infection of the Lamina Propria but Not Epithelium of the Upper Respiratory Tract in MyD88-Deficient Mice.

To understand protective immune responses against the onset of group A Streptococcus respiratory infection, we investigated whether MyD88 KO mice were susceptible to acute infection through transmission. After commingling with mice that had intranasal group A Streptococcus (GAS) inoculation, MyD88-/- recipient mice had increased GAS loads in the nasal cavity and throat that reached a mean throat colonization of 6.3 × 106 CFU/swab and mean GAS load of 5.2 × 108 CFU in the nasal cavity on day 7. Beyond day 7, MyD88-/- recipient mice became moribund, with mean 1.6 × 107 CFU/swab and 2.5 × 109 CFU GAS in the throat and nasal cavity, respectively. Systemic GAS infection occurred a couple of days after the upper respiratory infection. GAS infects the lip, the gingival sulcus of the incisor teeth, and the lamina propria of the turbinate but not the nasal cavity and nasopharyngeal tract epithelia, and C57BL/6J recipient mice had no or low levels of GAS in the nasal cavity and throat. Direct nasal GAS inoculation of MyD88-/- mice caused GAS infection, mainly in the lamina propria of the turbinate. In contrast, C57BL/6J mice with GAS inoculation had GAS bacteria in the nasal cavity but not in the lamina propria of the turbinates. Thus, MyD88-/- mice are highly susceptible to acute and lethal GAS infection through transmission, and MyD88 signaling is critical for protection of the respiratory tract lamina propria but not nasal and nasopharyngeal epithelia against GAS infection.

Type IV Pili of Streptococcus sanguinis Contribute to Pathogenesis in Experimental Infective Endocarditis.

Streptococcus sanguinis is a common cause of infective endocarditis (IE). Efforts by research groups are aimed at identifying and characterizing virulence factors that contribute to the ability of this organism to cause IE. This Gram-positive pathogen causes heart infection by gaining access to the bloodstream, adhering to host extracellular matrix protein and/or platelets, colonizing the aortic endothelium, and incorporating itself into the aortic vegetation. While many virulence factors have been reported to contribute to the ability of S. sanguinis to cause IE, it is noteworthy that type IV pili (T4P) have not been described to be a virulence factor in this organism, although S. sanguinis strains typically encode these pili. Type IV pili are molecular machines that are capable of mediating diverse virulence functions and surface motility. T4P have been shown to mediate twitching motility in some strains of S. sanguinis, although in most strains it has been difficult to detect twitching motility. While we found that T4P are dispensable for direct in vitro platelet binding and aggregation phenotypes, we show that they are critical to the development of platelet-dependent biofilms representative of the cardiac vegetation. We also observed that T4P are required for in vitro invasion of S. sanguinis into human aortic endothelial cells, which indicates that S. sanguinis may use T4P to take advantage of an intracellular niche during infection. Importantly, we show that T4P of S. sanguinis are critical to disease progression (vegetation development) in a native valve IE rabbit model. The results presented here expand our understanding of IE caused by S. sanguinis and identify T4P as an important virulence factor for this pathogen. IMPORTANCE This work provides evidence that type IV pili produced by Streptococcus sanguinis SK36 are critical to the ability of these bacteria to attach to and colonize the aortic heart valve (endocarditis). We found that an S. sanguinis type IV pili mutant strain was defective in causing platelet-dependent aggregation in a 24-h infection assay but not in a 1-h platelet aggregation assay, suggesting that the type IV pili act at later stages of vegetation development. In a rabbit model of disease, a T4P mutant strain does not develop mature vegetations that form on the heart, indicating that this virulence factor is critical to disease and could be a target for IE therapy.

TGF-ß regulation of the uPA/uPAR axis modulates mesothelial-mesenchymal transition (MesoMT).

Pleural fibrosis (PF) is a chronic and progressive lung disease which affects approximately 30,000 people per year in the United States. Injury and sustained inflammation of the pleural space can result in PF, restricting lung expansion and impairing oxygen exchange. During the progression of pleural injury, normal pleural mesothelial cells (PMCs) undergo a transition, termed mesothelial mesenchymal transition (MesoMT). While multiple components of the fibrinolytic pathway have been investigated in pleural remodeling and PF, the role of the urokinase type plasminogen activator receptor (uPAR) is unknown. We found that uPAR is robustly expressed by pleural mesothelial cells in PF. Downregulation of uPAR by siRNA blocked TGF-ß mediated MesoMT. TGF-ß was also found to significantly induce uPA expression in PMCs undergoing MesoMT. Like uPAR, uPA downregulation blocked TGF-ß mediated MesoMT. Further, uPAR is critical for uPA mediated MesoMT. LRP1 downregulation likewise blunted TGF-ß mediated MesoMT. These findings are consistent with in vivo analyses, which showed that uPAR knockout mice were protected from S. pneumoniae-mediated decrements in lung function and restriction. Histological assessments of pleural fibrosis including pleural thickening and α-SMA expression were likewise reduced in uPAR knockout mice compared to WT mice. These studies strongly support the concept that uPAR targeting strategies could be beneficial for the treatment of PF.

The perils of penile enhancement: case report of a fulminant penile infection.

BACKGROUND: Penile enhancement with injectable agents is a rising trend and yet has received little scientific attention despite the potential for serious complications. These include cosmetic, functional and systemic complications that may require complex penile reconstructive surgery. We report a case of delayed severe infection following penile filler insertion leading to multi-organ failure and intensive care support. CASE PRESENTATION: A 31-year-old man presented with fevers and progressive pain and swelling of the penile shaft, 3 days after unprotected sexual intercourse. The patient received subcutaneous hyaluronic filler injections at a cosmetic clinic for penile enlargement two months prior to presentation. Relevant social history include polysubstance abuse and multiple sexual partners. Physical examination revealed gross penile oedema and erythema, with a ventral curvature of the penile shaft and a superficial abrasion on the distal ventral penile shaft. Within 24 h the patient developed septic shock with anuria, hypotension and fevers to 40 °C, requiring transfer to the Intensive Care Unit (ICU) for vasopressor and inotropic support. Intraoperative penile exploration revealed multiple pus stained fillers which were drained and grew Streptococcus Pyogenes on cultures. There was no abscess or evidence of necrotising fasciitis intraoperatively. The patient improved with intravenous antibiotics and was stepped down from the ICU after four days and discharged on day eight. One month post admission there was significant superficial skin loss to both ventral and lateral aspect of the penis, with healthy granulation tissue at the base. The patient opted for conservative management with regular dressings. He reported normal sexual and urinary function three months post admission. CONCLUSION: This is the first published case of sepsis from a penile infection in the context of hyaluronic acid penile fillers. In an era of escalating demand for penile cosmetic procedures, there is an increasing need for early recognition and appropriate management of penile filler infections. We report an unusual case of a localised penile infection rapidly progressing to sepsis with multi-organ failure requiring intensive care support. The case demonstrates early surgical intervention with targeted antimicrobials can result in successful eradication of infection, with satisfactory cosmetic and functional outcomes for patients.

Outbreaks of Streptococcus gallolyticus subsp. pasteurianus in Goslings Characterized by Central Nervous Symptoms.

The present report describes outbreaks of Streptococcus gallolyticus subsp. pasteurianus in young geese flocks in Austria. The flocks, comprising 160-1450 goslings of 2-3 wk of age, experienced increased mortalities The clinical signs were characterized by severe central nervous symptoms, namely leg paddling and torticollis. The postmortem investigation revealed hepatitis, splenitis, and a low amount of liquid fluid in the coelomic cavity. Livers were of fragile texture, with white necrotic areas. The latter were also found in spleens. No macroscopic lesions were seen in brains. Bacteriologic investigation followed by bacterial identification by matrix-assisted laser desorption time-of-flight mass spectrometry and phylogenetic analysis of the partial 16S rRNA region revealed the presence in heart, liver, spleen, and brain of S. gallolyticus subsp. pasteurianus. Histologic investigation revealed multifocal necrosis in liver and spleen samples together with infiltration of mononuclear cells and heterophilic granulocytes. Furthermore, in the lesions, coccoid bacteria could be identified. No histopathologic changes were observed in brain samples from goslings, except in one bird in which accumulation of coccoid bacteria in blood vessels of the brain samples was present. Antibiotic sensitivity tests revealed identical profiles for all strains, which were susceptible to penicillins, cephalosporins, chloramphenicol, imipenem, and tylosin. However, resistance was found against quinolones, aminoglycosides, tetracycline, and trimethoprim-sulfamethoxazole, which are commonly used to treat infections with gram-positive bacteria.

Reporte de caso­Brotes de Streptococcus gallolyticus subsp. pasteurianus en gansitos caracterizados por síntomas nerviosos centrales. El presente informe describe brotes de Streptococcus gallolyticus subsp. pasteurianus en parvadas de gansos jóvenes en Austria. Las bandadas, que comprendían entre 160 a 1450 gansos de 2 a 3 semanas de edad, experimentaron aumento de la mortalidad. Los signos clínicos se caracterizaron por síntomas severos del sistema nervioso central, incluyendo, movimientos de pataleo y tortícolis. La investigación post mórtem reveló hepatitis, esplenitis y la presencia de líquido en la cavidad celómica en poca cantidad. Los hígados presentaron textura frágil, con áreas necróticas blancas. Estos últimos también se encontraron en bazos. No se observaron lesiones macroscópicas en el cerebro. La investigación bacteriológica seguida de la identificación bacteriana mediante espectrometría de masas MALDI-TOF y el análisis filogenético de la región parcial de ARNr 16S revelaron la presencia en el corazón, el hígado, el bazo y en el cerebro de S. gallolyticus subsp. pasteurianus. La investigación histológica reveló necrosis multifocal en muestras de hígado y bazo junto con infiltración de células mononucleares y granulocitos heterófilos. Además, en las lesiones se pudieron identificar bacterias de morfología cocoide. No se observaron cambios histopatológicos en muestras de cerebro de los gansitos, excepto en un ave en la que se observó acumulación de bacterias cocoides en los vasos sanguíneos de las muestras de cerebro. Las pruebas de sensibilidad a los antibióticos revelaron perfiles idénticos para todas las cepas, que eran susceptibles a penicilinas, cefalosporinas, cloranfenicol, imipenem y tilosina. Sin embargo, se encontró resistencia contra quinolonas, aminoglucósidos, tetraciclina y trimetoprim-sulfametoxazol, que se usan comúnmente para tratar infecciones con bacterias grampositivas.

Baicalein Ameliorates Streptococcus suis-Induced Infection In Vitro and In Vivo.

As an important zoonotic pathogen, Streptococcus suis (S. suis) infection has been reported to be a causative agent for variety of diseases in humans and animals, especially Streptococcal toxic shock-like syndrome (STSLS), which is commonly seen in cases of severe S. suis infection. STSLS is often accompanied by excessive production of inflammatory cytokines, which is the main cause of death. This calls for development of new strategies to avert the damage caused by STSLS. In this study, we found for the first time that Baicalein, combined with ampicillin, effectively improved severe S. suis infection. Further experiments demonstrated that baicalein significantly inhibited the hemolytic activity of SLY by directly binding to SLY and destroying its secondary structure. Cell-based assays revealed that Baicalein did not exert toxic effects and conferred protection in S. suis-infected cells. Interestingly, compared with ampicillin alone, Baicalein combined with ampicillin resulted in a higher survival rate in mice severely infected with S. suis. At the same time, we found that baicalein can be combined with meropenem against MRSA. In conclusion, these results indicate that baicalein has a good application prospect.

Potential factors involved in the early pathogenesis of Streptococcus uberis mastitis: a review.

Bovine mastitis is an inflammation of the mammary gland, which could be the result of allergy, physical trauma, or invasion by pathogens as Streptococcus uberis. This pathogen is an environmental pathogen associated with subclinical and clinical intramammary infection (IMI) in both lactating and non-lactating cows, which can persist in the udder and cause a chronic infection in the mammary gland. In spite of the important economic losses and increased prevalence caused by S. uberis mastitis, virulence factors involved in bacterial colonization of mammary glands and the pathogenic mechanisms are not yet clear. In the last 30 years, several studies have defined adherence and internalization of S. uberis as the early stages in IMI. S. uberis adheres to and invades into mammary gland cells, and this ability has been observed in in vitro assays. Until now, these abilities have not been determined in vivo challenges since they have been difficult to study. Bacterial surface proteins are able to bind to extracellular matrix protein components such as fibronectin, collagen and laminin, as well as proteins in milk. These proteins play a role in adhesion to host cells and have been denominated microbial surface components recognizing adhesive matrix molecules (MSCRAMMs). This article aims to summarize our current knowledge on the most relevant properties of the potential factors involved in the early pathogenesis of S. uberis mastitis.

THREE CASES OF ACUTE BACTERIAL SEPSIS IN PYGMY HIPPOPOTAMUS (CHOEROPSIS LIBERIENSIS) CALVE SIBLINGS.

A multiparous pygmy hippopotamus (Choeropsis liberiensis) dam produced three consecutive calves that died acutely at 13-15 wk of age from bacterial sepsis, for which diagnostic and therapeutic intervention was not possible. Streptococcus iniae (Cases 1 and 3), Escherichia coli (Case 2), and an unidentified member of the family Pasteurellaceae (Case 1) were identified in postmortem tissues through bacterial culture followed by standard and molecular identification methods. After the loss of two calves, a series of vaccinations were administered to the dam during the third pregnancy to enhance transplacental and colostral transfer of antibodies to the calf. The third calf did not survive, and the source of the bacterial infection in these three calves was undetermined. Prior to and after the birth of the fourth calf, nutritional and nutraceutical supplements were provided to the dam and calf. Additionally, pest control around the barn was enhanced. The fourth calf survived. Pygmy hippopotamus calves at the age of 13-15 wk may have increased susceptibility to bacterial infection, possibly due to waning maternally derived immunity. The findings in these cases, combined with a previous association of S. iniae in pygmy hippopotamus deaths, suggest that this bacterium is an especially important pathogen of the endangered pygmy hippopotamus.