A randomised, double-blinded, controlled trial to determine the efficacy of combined therapy of oclacitinib and marine oil extract PCSO-524 in dogs with atopic dermatitis.

BACKGROUND: Polyunsaturated fatty acids (PUFA) can be beneficial in the management of canine atopic dermatitis (cAD). A commercial product PCSO-524 containing PUFA has demonstrated anti-inflammatory effects in dogs. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of PCSO-524, in combination with oclacitinib in dogs with cAD. ANIMALS: Seventeen client-owned dogs with cAD. MATERIALS AND METHODS: A randomised, double-blinded, controlled trial. All dogs were treated with oclacitinib (0.4-0.6 mg/kg) twice a day for 14 days, then once a day until Day (D)42. They were randomly divided into two groups: PCSO-524 (n = 9) and sunflower oil (n = 8). Clinical status was assessed by Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and pruritus Visual Analog Scale (pVAS) at baseline (D0), D14, D28 and D42. Trans epidermal water loss (TEWL) was measured at the same time points. RESULTS: CADESI scores decreased significantly after treatment and there was a significant difference between the PCSO-524 and the control group at D28 (p = 0.04) and D42 (p = 0.03). The PCSO-524 group also demonstrated a significantly decreased pVAS on D28 and D42 (p < 0.001 and p < 0.001) compared to D0, while significant differences were observed in the control group at D14 and D28 (p < 0.01 and p = 0.04) and not at D42 (p = 0.12). The mean TEWL showed a significant decrease at D28 and D42 in the PCSO-524 group, compared to the control group (p = 0.002 and p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: The combination of PCSO-524 and oclacitinib may help to alleviate the rebound effect that occurs when tapering down the dosage of oclacitinib, as compared to using oclacitinib alone for the management of cAD.

Antibiotic-resistant status and pathogenic clonal complex of canine Streptococcus canis-associated deep pyoderma.

BACKGROUND: Streptococcus canis causes deep pyoderma in canines, which raises concerns about the risk of isolates from lesions acquiring an antibiotic-resistant phenotype. It is necessary to identify effective antibiotics and the characteristics of the pathogenic cluster for S. canis-associated deep pyoderma. RESULTS: The signalment, molecular typing, and antibiotic-resistant status of S. canis isolated from deep pyoderma lesions (27 strains) and oral cavities (26 strains) were analyzed. Older dogs tended to have S. canis-associated deep pyoderma (15 of 27 dogs over 10 years old). Veterinarians chose quinolones for 10/16 cases (63%), even though the rate of quinolone-resistant strains of S. canis is 38-59%. Although 70% of the strains showed resistance to three or more antibiotic classes (37/53), 94% (50/53) strains showed sensitivity for penicillins. We also identified ß-lactamase activity among penicillin-resistant strains of S. canis. Clonal complex 13 (CC13) was detected only in lesions and formed independent clusters in the phylogenetic tree. One strain of CC13 was resistant to the anti-methicillin-resistant Staphylococcus aureus drugs, vancomycin and linezolid. CONCLUSION: Although antibiotic-resistant strains of S. canis are isolated at a high rate, they can currently be treated with ß-lactamase-inhibiting penicillins. CC13 may be a pathogenic cluster with high levels of antibiotics resistance.

Guest edited collection serological study of SARS-CoV-2 antibodies in japanese cats using protein-A/G-based ELISA.

BACKGROUND: Little is known about the epidemic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cats in Japan due to insufficiently reliable seroepidemiological analysis methods that are easy to use in cats. RESULTS: We developed a protein-A/G-based enzyme-linked immunosorbent assay (ELISA) to detect antibodies against SARS-CoV-2 in cats. The assay was standardized using positive rabbit antibodies against SARS-CoV-2. The ELISA results were consistent with those of a conventional anti-feline-immunoglobulin-G (IgG)-based ELISA. To test the protein-A/G-based ELISA, we collected blood samples from 1,969 cats that had been taken to veterinary clinics in Japan from June to July 2020 and determined the presence of anti-SARS-CoV-2 antibodies. Nine cats were found to have SARS-CoV-2 S1-specific IgG, of which 4 had recombinant receptor-binding domain-specific IgG. Of those 9 samples, one showed neutralizing activity. Based on these findings, we estimated that the prevalence of SARS-CoV-2 neutralizing antibodies in cats in Japan was 0.05% (1/1,969 samples). This prevalence was consistent with the prevalence of neutralizing antibodies against SARS-CoV-2 in humans in Japan according to research conducted at that time. CONCLUSIONS: Protein-A/G-based ELISA has the potential to be a standardized method for measuring anti-SARS-CoV-2 antibodies in cats. The infection status of SARS-CoV-2 in cats in Japan might be linked to that in humans.

Epithelial-immune crosstalk with the skin microbiota in homeostasis and atopic dermatitis - a mini review.

The skin is a complex and dynamic ecosystem, wherein epithelial cells, immune cells and the skin microbiota actively interact and maintain barrier integrity and functional immunity. Skin microbes actively tune the functions of the resident immune cells. Dysbiosis - alterations in the resident microbiota - leads to the dysregulation of host immunity. Microbiome analyses in humans and dogs with atopic dermatitis (AD) have shown shifts in microbial diversity, and in particular, an increased proportion of staphylococci. Monogenic diseases that manifest AD-like symptoms provide insights into the pathogenesis of AD and the mechanisms of dysbiosis, from both the epithelial and immunological perspectives. The symbiotic relationships between the host and microbiota must be maintained constitutively. Detailed mechanisms of how host immunity regulates commensal bacteria in the steady state have been reported. The skin harbours multiple tissue-resident immune cells, including both innate and adaptive immune cells. Recent studies have highlighted the fundamental role of innate lymphoid cells (ILCs) in the maintenance of barrier functions and tissue homeostasis. ILCs directly respond to tissue-derived signals and are instrumental in barrier immunity. Epithelial cells produce alarmins such as thymic stromal lymphopoietin (TSLP) and interleukins (IL)-33 and IL-25, all of which activate group 2 ILCs (ILC2s), which produce type 2 cytokines, such as IL-5 and IL-13, boosting type 2 immune reactions. Dysregulation of the epithelial-ILC crosstalk results in allergic inflammation. This review highlights our understanding of the active interactions between the host epithelial and immune cells, and microbiota, providing a foundation for novel therapeutic strategies for inflammatory skin diseases.

La peau est un écosystème complexe et dynamique, tandis que les cellules épithéliales, les cellules immunitaires et le microbiote cutané interagissent activement et maintiennent l'intégrité de la barrière et de l'immunité. Les microbes cutanés règlent activement les fonctions des cellules immunitaires résidentes. La dysbiose - altérations du microbiote résident - mène à la dérégulation de l'immunité de l'hôte. Les analyses du microbiome chez l'homme et le chien avec dermatite atopique (AD) ont montré les shifts de diversité microbienne, et en particulier, une augmentation de la proportion de staphylocoques. Les maladies monogéniques qui manifestent des symptômes AD-like fournissent des données sur la pathogénie de AD et des mécanismes de dysbiose, à la fois de perspectives épithéliales et immunologiques. Les relations symbiotiques entre l'hôte et le microbiote doit être maintenu constitutivement. Les mécanismes détaillés de comment l'immunité de l'hôte régule les bactéries commensales dans l'état ont été décrits. La peau possède différentes cellules immunitaires résidents comprenant à la fois des cellules des systèmes immunitaires inné et adaptatif. Des études récente ont montré le rôle fondamental des cellules lymphoïdes innées (ILCs) dans le maintien des fonctions barrières et homéostasie tissulaire. Les ILCs répondent directement aux signaux dérivés des tissus et sont instrumentaux dans l'immunité de barrière. Les cellules épithéliales produisent des alamines tels que TSLP (thymic stromal lymphopoietin) et interleukines (IL)-33 et IL-25, toutes activant les ILCs du groupe 2 (ILC2s), produisent des cytokines de type 2 telles que IL-5 et IL-13, boostant l'immunité de type 2. La dérégulation des résultats de epithelial-ILC résulte en une inflammation allergique. Cette revue insiste sur nos connaissances sur les interactions actives entre les cellules immunitaires et épithéliales de l'hôte et le microbiote, fournissant une base pour de nouvelles stratégies thérapeutiques pour les maladies cutanés inflammatoires.

La piel es un ecosistema complejo y dinámico, en el que las células epiteliales, las células inmunitarias y la microbiota cutánea interactúan activamente y mantienen la integridad de la barrera y la inmunidad funcional. Los microbios de la piel sintonizan activamente las funciones de las células inmunitarias residentes. La disbiosis (alteraciones en la microbiota residente) conduce a la disregulación de la inmunidad del huésped. Los análisis de microbiomas en humanos y perros con dermatitis atópica (AD) han mostrado cambios en la diversidad microbiana y, en particular, una mayor proporción de estafilococos. Las enfermedades monogénicas que manifiestan síntomas similares a la AD proporcionan información sobre la patogénesis de la AD y los mecanismos de la disbiosis, tanto desde la perspectiva epitelial como inmunológica. Las relaciones simbióticas entre el huésped y la microbiota deben mantenerse de manera constitutiva. Mecanismos detallados de cómo la inmunidad del huésped regula las bacterias comensales en el estado normal han sido descritos. La piel alberga múltiples células inmunitarias residentes en los tejidos, incluidas células inmunitarias tanto innatas como adaptativas. Estudios recientes han destacado el papel fundamental de las células linfoides innatas (ILCs) en el mantenimiento de las funciones de barrera y la homeostasis tisular. Las ILCs responden directamente a señales derivadas de tejidos y son fundamentales en la inmunidad de barrera. Las células epiteliales producen alarminas como la linfopoyetina del estroma tímico (TSLP) y las interleuquinas (IL) -33 e IL-25, todas las cuales activan las ILCs del grupo 2 (ILC2s), que producen citocqunas de tipo 2, como IL-5 e IL-13, estimulando las reacciones inmunes de tipo 2. La disregulación de la interacción epitelio-ILCs da como resultado una inflamación alérgica. Esta revisión destaca nuestra comprensión de las interacciones activas entre las células epiteliales e inmunes del huésped y la microbiota, proporcionando una base para nuevas estrategias terapéuticas en enfermedades inflamatorias de la piel.

A pele é um ecossistema complexo e dinâmico, em que as células epiteliais, as células imunológicas e a microbiota cutânea interagem ativamente e mantêm a integridade da barreira e a imunidade funcional. Os microrganismos da pele ajustam ativamente as funções das células imunes residentes. Disbiose - alterações na microbiota residente - leva à desregulação da imunidade do hospedeiro. As análises de microbioma em humanos e cães com dermatite atópica (DA) demonstraram mudanças na diversidade microbiana e, em particular, um aumento na proporção de estafilococos. Doenças monogênicas que manifestam sintomas semelhantes aos da DA fornecem informações sobre a patogênese da DA e os mecanismos da disbiose, tanto sob o ponto de vista epitelial quanto imunológico. As relações simbióticas entre o hospedeiro e a microbiota devem ser mantidas constitutivamente. Mecanismos detalhados de como a imunidade do hospedeiro regula as bactérias comensais no estado estacionário foram relatados. A pele abriga várias células imunes residentes no tecido, incluindo células imunes inatas e adaptativas. Estudos recentes têm destacado o papel fundamental das células linfoides inatas (ILCs) na manutenção das funções de barreira e homeostase tecidual. Os ILCs respondem diretamente aos sinais derivados de tecidos e são fundamentais para a imunidade de barreira. As células epiteliais produzem alarminas, como linfopoietina estromal tímica (TSLP) e interleucinas (IL) -33 e IL-25, todas ativando ILCs do grupo 2 (ILC2s), que produzem citocinas tipo 2, como IL-5 e IL-13, estimulando as reações imunológicas do tipo 2. A desregulação da comunicação epitelial-ILC resulta em inflamação alérgica. Esta revisão destaca nossa compreensão das interações ativas entre as células epiteliais e imunológicas do hospedeiro e microbiota, fornecendo uma base para novas estratégias terapêuticas para doenças inflamatórias da pele.

Efficacy of olanexidine gluconate in canine superficial pyoderma: a randomised, single-blinded controlled trial.

BACKGROUND: Topical treatments can be beneficial for managing canine superficial pyoderma. A novel antiseptic agent, olanexidine gluconate, has become available recently for use in humans, and its efficacy for canine pyoderma as topical therapy is unknown. OBJECTIVE: The antimicrobial effect of olanexidine was evaluated using minimal inhibitory concentration (MIC) towards Staphylococcus pseudintermedius. Furthermore, its clinical efficacy in canine superficial pyoderma was assessed in a randomized, single-blinded study. ANIMALS: Twenty-eight client-owned dogs with atopic dermatitis and superficial pyoderma. METHODS AND MATERIALS: The MIC of olanexidine was determined for S. pseudintermedius isolates (n=73) by serial dilution of 96-well broth microdilution method. Regarding the clinical trial, all recruited dogs were randomized into two groups; one treated with 1.5% olanexidine spray once daily and the other with a 3% chlorhexidine shampoo once a week for 2 times, respectively. Clinical assessment was performed at days 0 and 14 according to the guidelines of the Japanese Society of Antimicrobials for Animals. RESULTS: The MIC values for methicillin-resistant S. pseudintermedius (MRSP) and methicillin-sensitive S. pseudintermedius (MSSP) were 0.23 µg/ml and 0.24 µg/ml (P =0.9), respectively. In clinical trial, olanexidine and chlorhexidine showed substantial improvement in clinical presentation compared to the baseline. CONCLUSIONS AND CLINICAL IMPORTANCE: Olanexidine showed comparable efficacy to chlorhexidine (P=0.73). Moreover, the MIC against S. pseudintermedius indicated high bactericidal activity, which was supported by the topical effectiveness of olanexidine.

Influence of hospital size on antimicrobial resistance and advantages of restricting antimicrobial use based on cumulative antibiograms in dogs with Staphylococcus pseudintermedius infections in Japan.

BACKGROUND: Antimicrobial resistance in Staphylococcus pseudintermedius (SP) and the prevalence of meticillin-resistant SP (MRSP) is increasing in dogs worldwide. OBJECTIVES: To evaluate the influence of hospital size on antimicrobial resistance of SP and whether restricted use of antimicrobials based on antibiograms could reduce the identification of antimicrobial resistance in SP from infected dogs. METHODS AND MATERIALS: In Study 1, a total of 2,294 SP isolates from dogs with pyoderma (n = 1,858, 52 hospitals) or otitis externa (OE; n = 436, 44 hospitals) taken between 2017 and 2019 were analysed. Clinics were categorised into small, medium and large based on numbers of practicing veterinary surgeons. In Study 2, a cumulative antibiogram was constructed for 12 antimicrobials from one large veterinary clinic from 2017 to 2018. Referring to this antibiogram, the clinic introduced strict antimicrobial selection criteria to treat dogs with pyoderma and OE, starting in 2018. RESULTS: MRSP was identified in 981 dogs (42.8%). In large clinics, the isolation rate of MRSP was 51.1% (404 of 791), which was significantly higher (P < 0.01) than in small clinics with less than two veterinary practitioners (34.0%, 154 of 453). In the antibiogram study, the susceptibility rates of oxacillin (MPIPC, 61.5%), cefpodoxime (CPDX, 55.8%) and minocycline (MINO, 55.8%) were significantly higher in 2019 (n = 52) than in 2017 to 2018 (n = 54; MPIPC, 37.0%; CPDX, 33.3%; MINO, 20.4%; P < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Hospital size could affect the isolation rate of MRSP in dogs. Restricted use of antimicrobials for over a year based on cumulative antibiograms could reduce the resistance rate of multiple antimicrobials in SP isolated from dogs with pyoderma and OE.

Efficacy and safety of 0.0584% hydrocortisone aceponate topical spray and systemic oclacitinib combination therapy in dogs with atopic dermatitis: a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Oclacitinib is an effective systemic therapy for dogs with atopic dermatitis (AD). Few studies have evaluated concurrent topical treatment with oclacitinib in dogs. OBJECTIVES: To evaluate the efficacy and safety of combination therapy of oclacitinib and 0.0584% hydrocortisone aceponate (HCA) spray in dogs with AD. ANIMALS: Eighteen dogs with AD. METHODS AND MATERIALS: This study was a randomized, double-blinded, placebo-controlled trial. All dogs were treated with oclacitinib (0.4-0.6 mg/kg twice daily for 14 days, then once daily for 14 days) and randomized to receive either HCA spray or placebo spray, applied once daily for seven days then every other day through to Day (D)28. Clinical assessments included the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-4) and the pruritus Visual Analog Scale (PVAS) every seven days, and blood and urine tests every 14 days. RESULTS: The mean CADESI-4 and PVAS scores were significantly reduced on D7 and D14 compared to D0 in both groups (P < 0.05). From D14 to D21, CADESI-4 and PVAS scores were significantly increased in the placebo group (P < 0.005), and not in the HCA-treated group. The mean reduction from baseline of the HCA-treated group was significantly higher than that of the placebo group for the PVAS and CADESI-4 on D21 (59.9% versus 27.6%, P = 0.0216) and D28 (56.0% versus 30.5%, P = 0.0109), respectively. One dog in the HCA-treated group was withdrawn as a consequence of developing diarrhoea. CONCLUSION: Topical application of 0.0584% HCA spray may be useful for preventing exacerbation of pruritus and clinical lesions when tapering oclacitinib therapy in dogs with AD.

IgE reactivity to fish allergens from Pacific cod (Gadus macrocephalus) in atopic dogs.

BACKGROUND: IgE reactivity to fish allergens in atopic dogs, which are used as models for food allergy, has not been elucidated to date. We investigated IgE reactivity to crude extracts and purified allergens derived from the Pacific cod (Gadus macrocephalus) in atopic dogs to identify the allergenic proteins of cod. RESULTS: The levels of specific IgE to crude cod extracts were measured in the sera of 179 atopic dogs, including 27 dogs with cod allergy, using enzyme-linked immunosorbent assay (ELISA). Specific IgE to crude cod extracts were present in 36 (20%) of the 179 atopic dogs and in 12 (44%) of the 27 dogs with cod allergy. The allergens in crude cod extracts were analyzed by ELISA, immunoblotting, and liquid chromatography-tandem mass spectrometry. In allergen component analysis, IgE reactivity to tropomyosin and enolase was observed in the sera of dogs with cod allergy. IgE reactivity to parvalbumin, collagen, and tropomyosin was evaluated using the sera of atopic dogs that tested positive for specific IgE to crude cod extracts. Among the 36 dogs with IgE reactivity to crude cod extracts, 9 (25%), 14 (39%), and 18 (50%) dogs tested positive for specific IgE to parvalbumin, collagen, and tropomyosin, respectively. CONCLUSIONS: The IgE reactivity to cod allergens observed in dogs was similar to that in humans, and this finding further supports the use of atopic dogs with fish allergy as a model for fish allergy in humans.

Clinical and histopathological presentation and successful treatment with ciclosporin for canine sarcoidosis: a case report.

BACKGROUND: Sarcoidosis is a granulomatous disease histologically characterized by naked granulomas in various mammals. Canine sarcoidosis is a rare disease which can cause nonpruritic papule, plaques and nodules on the trunk, neck, face and ear; it is usually treated with corticosteroids. To date, there are no published reports on alternatives to corticosteroids treatment. OBJECTIVES: To report a case of canine cutaneous sarcoidosis successfully treated with oral ciclosporin. ANIMAL: An 11-year-old beagle dog was presented with multiple pleomorphic plaques on the lateral thighs and dorsal trunk. METHODS AND MATERIALS: Skin punch biopsy specimen were collected and analysed via routine histological examination and immunohistochemistry. After 14 weeks of oral ciclosporin treatment, repeat skin biopsy specimens were collected. RESULTS: Histopathological examination revealed noncaseating epithelioid cell granuloma formation in the dermis. Dermal epithelioid cells were positive for CD18 and Iba1, but not for CD3, CD20 and E-cadherin based on immunohistochemistry findings. Acid-fast bacteria, fungi and Leishmania spp. were not detected by special stains, culture or polymerase chain reaction. An initial two week treatment with immunosuppressive doses of oral prednisolone and doxycycline was not effective. Skin lesions were almost in remission after 14 weeks of oral ciclosporin treatment without adverse events. Histologically, the dermal granulomatous lesions regressed and were replaced by fibrous tissues after ciclosporin treatment. CONCLUSIONS AND CLINICAL RELEVANCE: This case report describes the clinical and histopathological presentation including immunohistochemistry and treatment outcome of a case of canine sarcoidosis Ciclosporin may be an effective alternative to corticosteroids for treating canine sarcoidosis.

Piperacillin and ceftazidime produce the strongest synergistic phage-antibiotic effect in Pseudomonas aeruginosa.

The combined use of phage and antibiotics can show synergistic antimicrobial effects, so-called phage-antibiotic synergy (PAS). Here, we screened and examined PAS against Pseudomonas aeruginosa in vitro. Testing four different phages infecting P. aeruginosa, phage KPP22 classified within the family Myoviridae genus Pbunavirus showed PAS with the widest range of antibiotics, and showed PAS with anti-Pseudomonas drugs such as piperacillin and ceftazidime. Thus, evidence suggests that the combined use of phage and antibiotics is a promising therapeutic strategy against P. aeruginosa infections, with consideration needed regarding the optimal selection and adequate application timing of these phages and antibiotics.

Staphylococcus aureus penetrate the interkeratinocyte spaces created by skin-infiltrating neutrophils in a mouse model of impetigo.

BACKGROUND: Impetigo is a bacterial skin disease characterized by intraepidermal neutrophilic pustules. Previous studies have demonstrated that exfoliative toxin producing staphylococci are isolated in the cutaneous lesions of human and canine impetigo. However, the mechanisms of intraepidermal splitting in impetigo remain poorly understood. OBJECTIVE: To determine how staphylococci penetrate the living epidermis and create intraepidermal pustules in vivo using a mouse model of impetigo. METHODS: Three Staphylococcus aureus strains harbouring the etb gene and three et gene negative strains were epicutaneously inoculated onto tape-stripped mouse skin. The skin samples were subjected to time course histopathological and immunofluorescence analyses to detect intraepidermal neutrophils and infiltrating staphylococci. To determine the role of neutrophils on intraepidermal bacterial invasion, cyclophosphamide (CPA) was injected intraperitoneally into the mice to cause leucopenia before the inoculation of etb gene positive strains. RESULTS: In mice inoculated with etb gene positive S. aureus, intraepidermal pustules resembling impetigo were detected as early as 4 h post-inoculation (hpi). Neutrophils in the epidermis were detected from 4 hpi, whereas intraepidermal staphylococci was detected from 6 hpi. The dimensions of the intraepidermal clefts created in mice inoculated with etb gene positive strains at 6 hpi were significantly larger than those in mice inoculated with et gene negative strains. In CPA treated mice, staphylococci or neutrophils were not detected in the deep epidermis until 6 hpi. CONCLUSION: Our findings indicate that intraepidermal neutrophils play an important role in S. aureus invasion into the living epidermis in a mouse model of impetigo.

Antimicrobial resistance and genotyping of Pseudomonas aeruginosa isolated from the ear canals of dogs in Japan.

The strong bond between dogs and their owners creates a close association that could result in the transfer of antibiotic-resistant bacteria from canines to humans, potentially leading to the spread of antimicrobial resistance genes. Pseudomonas aeruginosa, a common causative agent of persistent ear infections in dogs, is often resistant to multiple antibiotics. Assessing the antimicrobial resistance profile and genotype of P. aeruginosa is crucial for the appropriate use of veterinary pharmaceuticals. However, in recent years, few studies have been conducted on this bacterium in Japan. We determined the antimicrobial resistance profile and genotype of P. aeruginosa isolated from the ear canal of dogs in Japan in 2020. Analysis of antimicrobial resistance using disk diffusion tests indicated a high frequency of resistance to most antimicrobial agents. Particularly, 29 isolates from the ear canals of the 29 affected dogs (100%) were resistant to cefovecin, cefpodoxime, and florfenicol; however, they were susceptible to cefepime and piperacillin/tazobactam. Only 3.4, 10.3, and 10.3% of the isolates were resistant to ceftazidime, tobramycin, and gentamicin, respectively. Furthermore, upon analyzing the population structure using multilocus sequence typing, a considerably large clonal complex was not observed in the tested isolates. Three isolates, namely ST3881, ST1646, and ST532, were clonally related to the clinically isolated sequence types in Japan (such as ST1831, ST1413, ST1812, and ST1849), which is indicative of dog-to-human transmission. Considering the variation in antibiotic resistance compared to that reported by previous studies and the potential risk of dog-to-human transmission, we believe that the survey for antimicrobial resistance profile and population structure should be continued regularly. However, the prevalence of multidrug-resistant P. aeruginosa in dogs in Japan is not a crisis.

Anaphylaxis after vaccination for cats in Japan.

Severe adverse reactions in cats after vaccination were examined from 316 cases reported to the Ministry of Agriculture, Forestry and Fisheries (MAFF) in Japan during 15-year period from April 2004 to March 2019. We found that 130 (41%) showed anaphylaxis, and 99 (76%) of the 130 cases of anaphylaxis resulted in death. Veterinarians should be well prepared to deal with vaccine-associated anaphylaxis in cats. Bovine serum albumin (BSA) as indicator of purification was detected at high levels in commercially available feline vaccines. BSA might derive from fetal calf serum in culture media. This study provides useful information about anaphylaxis including critical details of the potential clinical signs associated with adverse events to feline vaccination.

Heterogeneous IgE reactivities to Staphylococcus pseudintermedius strains in dogs with atopic dermatitis, and the identification of DM13-domain-containing protein as a bacterial IgE-reactive molecule.

Staphylococcus pseudintermedius is one of the major pathogens causing canine skin infection. In canine atopic dermatitis (AD), heterogeneous strains of S. pseudintermedius reside on the affected skin site. Because an increase in specific IgE to this bacterium has been reported, S. pseudintermedius is likely to exacerbate the severity of canine AD. In this study, the IgE reactivities to various S. pseudintermedius strains and the IgE-reactive molecules of S. pseudintermedius were investigated. First, examining the IgE reactivities to eight strains of S. pseudintermedius using 141 sera of AD dogs, strain variation of S. pseudintermedius showed 10-63% of the IgE reactivities. This is different from the expected result based on the concept of Staphylococcus aureus clonality in AD patients. Moreover, according to the western blot analysis, there were more than four proteins reactive to IgE. Subsequently, the analysis of the common IgE-reactive protein at ∼15 kDa confirmed that the DM13-domain-containing protein was reactive in AD dogs, which is not coincident with any S. aureus IgE-reactive molecules. Considering these, S. pseudintermedius is likely to exacerbate AD severity in dogs, slightly different from the case of S. aureus in human AD.

Anaphylaxis after rabies vaccination for dogs in Japan.

Severe adverse reactions after rabies vaccination in dogs were examined from 317 cases reported to the Ministry of Agriculture, Forestry and Fisheries (MAFF) in Japan during 15-year period from April 2004 to March 2019. We found that 109 of the 317 dogs showed anaphylaxis (0.15/100,000 vaccinated dogs), and 71 of the 109 cases of anaphylaxis resulted in death (0.10/100,000 vaccinated dogs). We measured bovine serum albumin (BSA) in four commercially available rabies vaccines and found the levels ranged from 0.1 to 16.6 µg/dose. Our survey showed that the rate of anaphylaxis to rabies vaccines in dogs is rare, although some cases of anaphylaxis resulted in death. Veterinarians should be well prepared to deal with vaccine-associated anaphylaxis.

IgE reactivity to milk components in dogs with cutaneous adverse food reactions.

We investigated the IgE reactivity to crude and purified milk antigens in the sera of 112 dogs with cutaneous adverse food reactions (CAFRs). Of the 112 dogs, 33 (29%) had specific IgE for crude milk antigens. In the dogs with milk-specific IgE, IgE reactivity to casein, bovine serum albumin (BSA), α-lactalbumin, ß-lactoglobulin, and bovine IgG were 81%, 85%, 39%, 27%, and 35%, respectively. Casein and BSA may be important allergens in dogs with CAFRs. Some canine vaccines contain casein hydrolysate as a stabilizer and the pooled serum with anti-casein IgE showed IgE reactivity to the vaccines containing it. Information about IgE reactivity to casein in dogs with CAFRs could be useful for predicting adverse reactions to the vaccines including casein hydrolysate.

Author Correction: Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Therapeutic Potential of an Endolysin Derived from Kayvirus S25-3 for Staphylococcal Impetigo.

Impetigo is a contagious skin infection predominantly caused by Staphylococcus aureus. Decontamination of S. aureus from the skin is becoming more difficult because of the emergence of antibiotic-resistant strains. Bacteriophage endolysins are less likely to invoke resistance and can eliminate the target bacteria without disturbance of the normal microflora. In this study, we investigated the therapeutic potential of a recombinant endolysin derived from kayvirus S25-3 against staphylococcal impetigo in an experimental setting. First, the recombinant S25-3 endolysin required an incubation period of over 15 minutes to exhibit efficient bactericidal effects against S. aureus. Second, topical application of the recombinant S25-3 endolysin decreased the number of intraepidermal staphylococci and the size of pustules in an experimental mouse model of impetigo. Third, treatment with the recombinant S25-3 endolysin increased the diversity of the skin microbiota in the same mice. Finally, we revealed the genus-specific bacteriolytic effect of recombinant S25-3 endolysin against staphylococci, particularly S. aureus, among human skin commensal bacteria. Therefore, topical treatment with recombinant S25-3 endolysin can be a promising disease management procedure for staphylococcal impetigo by efficient bacteriolysis of S. aureus while improving the cutaneous bacterial microflora.

Spontaneous regression of canine papillomavirus type 2-related papillomatosis on footpads in a dog.

Persistent papillomatosis on footpads related to canine papillomavirus type 2 (CPV-2) infection has been described in dogs with immunocompromised condition. A 9-year-old, male French bulldog was presented with cauliflower-like nodules on the footpads of his left front leg. Histopathological examination revealed multiple finger-like projections of squamous epithelium with intranuclear inclusion bodies. Immunohistochemistry using an anti-bovine papillomavirus antibody demonstrated immunostaining in the keratinocytes. Partial genome DNA of CPV-2 was amplified from the lesion. Full genome sequence of CPV-2 in the subject showed 99.95% nucleotide identity with that of CPV-2 from the reference data. Two weeks after a biopsy, the skin lesion spontaneously regressed without any specific treatment. In non-immunocompromised dogs, CPV-2-related footpad papillomatosis could spontaneously resolve after a biopsy.

Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity.

Exfoliative toxins (ETs) are secreted virulence factors produced by staphylococci. These serine proteases specifically cleave desmoglein 1 (Dsg1) in mammals and are key elements in staphylococcal skin infections. We recently identified a new et gene in S. aureus O46, a strain isolated from ovine mastitis. In the present study, we characterized the new et gene at a genetic level and the enzymatic activity of the deduced protein. The S. aureus O46 genome was re-assembled, annotated and compared with other publicly available S. aureus genomes. The deduced amino acid sequence of the new et gene shared 40%, 53% and 59% sequence identity to those of ETA, ETB and ETD, respectively. The new et gene shared the same genetic vicinity and was similar in other S. aureus strains bearing this gene. The recombinant enzyme of the new et gene caused skin exfoliation in vivo in neonatal mice. The new et-gene was thus named ete, encoding a new type (type E) of exfoliative toxin. We showed that ETE degraded the extracellular segments of Dsg1 in murine, ovine and caprine epidermis, as well as in ovine teat canal epithelia, but not that in bovine epidermis. We further showed that it directly hydrolyzed human and swine Dsg1 as well as murine Dsg1α and Dsg1ß, but not canine Dsg1 or murine Dsg1γ. Molecular modeling revealed a correlation between the preferred orientation of ETE docking on its Dsg1 cleavage site and species-specific cleavage activity, suggesting that the docking step preceding cleavage accounts for the ETE species-specificity. This new virulence factor may contribute to the bacterial colonization on the stratified epithelia in certain ruminants with mastitis.