RESUMO
Pasteurella spp. can cause fatal zoonotic infections in humans. We performed a multicenter study to investigate the prevalence and clinical features of Pasteurella infections in South Korea during 2018â2022. We also conducted a collaborative systematic review and meta-analysis of the global burden of Pasteurella bacteremia. The study included 283 cases found an increasing trend in Pasteurella infections. Blood cultures were positive in 8/35 (22.9%) cases sampled, for overall bacteremia-associated rate of 2.8% (8/283). Aging was a significant risk factor for bacteremia (odds ratio 1.05 [95% CI 1.01-1.10]), according to multivariate analyses. For the meta-analysis, we included a total of 2,012 cases from 10 studies. The pooled prevalence of bacteremia was 12.4% (95% CI 7.3%-18.6%) and of mortality 8.4% (95% CI 2.7%-16.5%). Our findings reflect the need for greater understanding of the increase in Pasteurella infections and the global burden of Pasteurella bacteremia to determine appropriate case management.
Assuntos
Bacteriemia , Infecções por Pasteurella , Pasteurella , Animais , Humanos , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Infecções por Pasteurella/epidemiologia , Infecções por Pasteurella/microbiologia , Prevalência , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
An 81-year-old male patient in Germany had prosthetic valve endocarditis caused by Pasteurella dagmatis after a domestic cat bite. We surgically treated a paravalvular abscess and administered definitive antibiotic therapy consisting of penicillin G and levofloxacin. The patient was discharged from the intensive care unit in good condition 21 days after the surgery.
Assuntos
Antibacterianos , Endocardite Bacteriana , Infecções por Pasteurella , Pasteurella , Masculino , Idoso de 80 Anos ou mais , Humanos , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Animais , Alemanha , Infecções por Pasteurella/microbiologia , Infecções por Pasteurella/diagnóstico , Infecções por Pasteurella/tratamento farmacológico , Gatos , Antibacterianos/uso terapêutico , Pasteurella/isolamento & purificação , Pasteurella/genética , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/tratamento farmacológico , Próteses Valvulares Cardíacas/efeitos adversos , Próteses Valvulares Cardíacas/microbiologia , Resultado do TratamentoRESUMO
Pasteurella bettyae is a gram-negative bacillus sporadically involved in human infections; its main reservoirs are cats and dogs. A recent publication suggests the possibility of sexual transmission leading to genital infections in men who have sex with men. We report 9 cases in France of genital infection among this population.
Assuntos
Homossexualidade Masculina , Infecções por Pasteurella , Pasteurella , Humanos , Masculino , França/epidemiologia , Adulto , Infecções por Pasteurella/transmissão , Infecções por Pasteurella/microbiologia , Pasteurella/isolamento & purificação , Pasteurella/genética , Pasteurella/classificação , Pessoa de Meia-Idade , Adulto JovemRESUMO
Pasteurella multocida is a zoonotic pathogen causing serious diseases in humans and animals. Here, we report P. multocida from wildlife on China's Qinghai-Tibet plateau with a novel capsular serotype, forming a single branch on the core-genome phylogenetic tree: four strains isolated from dead Himalayan marmot (Marmota himalayana) and one genome assembled from metagenomic sequencing of a dead Woolly hare (Lepus oiostolus). Four of the strains were identified as subspecies multocida and one was septica. The mouse model showed that the challenge strain killed mice within 24 h at an infectious dose of less than 300 bacteria. The short disease course is comparable to septicemic plague: the host has died before more severe pathological changes could take place. Though pathological changes were relatively mild, cytokine storm was obvious with a significant rise of IL-12p70, IL-6, TNF-αand IL-10 (P < 0.05). Our findings suggested P. multocida is a lethal pathogen for wildlife on Qinghai-Tibet plateau, in addition to Yersinia pestis. Individuals residing within the M. himalayana plague focus are at risk for P. multocida infection, and public health warnings are necessitated.
Assuntos
Pasteurella multocida , Peste , Animais , Humanos , Camundongos , Tibet , Marmota/microbiologia , Pasteurella multocida/genética , Filogenia , Sorogrupo , China , Peste/microbiologia , Animais SelvagensRESUMO
Pasteurella multocida is a zoonotic conditional pathogen that infects multiple livestock species, causing substantial economic losses in the animal husbandry industry. An efficient markerless method for gene manipulation may facilitate the investigations of P. multocida gene function and pathogenesis of P. multocida. Herein, a temperature-sensitive shuttle vector was constructed using lacZ as a selection marker, and markerless glgB, opa, and hyaE mutants of P. multocida were subsequently constructed through blue-white colony screening. The screening efficiency of markerless deletion strains was improved by the lacZ system, and the method could be used for multiple gene deletions. However, the fur mutant was unavailable via this method. Therefore, we constructed a pheSm screening system based on mutated phenylalanine tRNA synthetase as a counterselection marker to achieve fur deletion mutant. The transformed strain was sensitive to 20 mM p-chloro-phenylalanine, demonstrating the feasibility of pheSm as a counter-selective marker. The pheSm system was used for markerless deletions of glgB, opa, and hyaE as well as fur that could not be screened by the lacZ system. A comparison of screening efficiencies of the system showed that the pheSm counterselection system was more efficient than the lacZ system and broadly applicable for mutant screening. The methods developed herein may provide valuable tools for genetic manipulation of P. multocida.IMPORTANCEPasteurella multocida is a highly contagious zoonotic pathogen. An understanding of its underlying pathogenic mechanisms is of considerable importance and requires efficient species-specific genetic tools. Herein, we propose a screening system for P. multocida mutants using lacZ or pheSm screening markers. We evaluated the efficiencies of both systems, which were used to achieve markerless deletion of multiple genes. The results of this study support the use of lacZ or pheSm as counterselection markers to improve counterselection efficiency in P. multocida. This study provides an effective genetic tool for investigations of the virulence gene functions and pathogenic mechanisms of P. multocida.
Assuntos
Pasteurella multocida , Animais , Pasteurella multocida/genética , Óperon Lac , Vetores Genéticos , FenilalaninaRESUMO
Fowl cholera is an infectious disease that affects both poultry and wild birds, characterized by hemorrhagic and septicemic symptoms, caused by Pasteurella multocida (P. multocida), and leading to substantial economic losses in the poultry sector. The development of genetic engineering vaccines against avian P. multocida encountered early-stage challenges due to the limited availability of effective gene editing tools. Presently, NgAgoDM-enhanced homologous recombination stands as a potent technique for achieving efficient gene knockout in avian P. multocida. Hence, this study employed NgAgoDM-enhanced homologous recombination to target and knockout hyaE (239-359aa), hyaD, hexABC, and hexD, denoted as ΔhyaE (239-359aa), ΔhyaD, ΔhexABC, and ΔhexD, respectively. Additionally, we generated a hyaD recovery strain with two point mutations, designated as mhyaD. Thus, this study systematically examined the impact of capsular synthetic gene clusters on the pathogenicity of P. multocida. Moreover, the study demonstrated the critical role of hyaD activity in the virulence of avian P. multocida. This study offers novel insights for enhancing attenuated vaccines further.
Assuntos
Infecções por Pasteurella , Pasteurella multocida , Doenças das Aves Domésticas , Pasteurella multocida/genética , Pasteurella multocida/patogenicidade , Animais , Infecções por Pasteurella/veterinária , Infecções por Pasteurella/microbiologia , Virulência/genética , Doenças das Aves Domésticas/microbiologia , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/genética , Recombinação Homóloga , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/genética , Técnicas de Inativação de Genes , Galinhas/microbiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Aves/microbiologia , Família Multigênica , Fatores de Virulência/genética , Aves Domésticas/microbiologiaRESUMO
Pasteurella multocida causes acute/chronic pasteurellosis in porcine, resulting in considerable economic losses globally. The draft genomes of two Indian strains NIVEDIPm17 (serogroup D) and NIVEDIPm36 (serogroup A) were sequenced. A total of 2182-2284 coding sequences (CDSs) were predicted along with 5-6 rRNA and 45-46 tRNA genes in the genomes. Multilocus sequence analysis and LPS genotyping showed the presence of ST50: genotype 07 and ST74: genotype 06 in NIVEDIPm17 and NIVEDIPm36, respectively. Pangenome analysis of 61 strains showed the presence of 1653 core genes, 167 soft core genes, 750 shell genes, and 1820 cloud genes. Analysis of virulence-associated genes in 61 genomes indicated the presence of nanB, exbB, exbD, ptfA, ompA, ompH, fur, plpB, fimA, sodA, sodC, tonB, and omp87 in all strains. The 61 genomes contained genes encoding tetracycline (54%), streptomycin (48%), sulphonamide (28%), tigecycline (25%), chloramphenicol (21%), amikacin (7%), cephalosporin (5%), and trimethoprim (5%) resistance. Multilocus sequence type revealed that ST50 was the most common (34%), followed by ST74 (26%), ST13 (24%), ST287 (5%), ST09 (5%), ST122 (3%), and ST07 (2%). Single-nucleotide polymorphism and core genome-based phylogenetic analysis clustered the strains into three major clusters. In conclusion, we described the various virulence factors, mobile genetic elements, and antimicrobial resistance genes in the pangenome of P. multocida of porcine origin, besides the rare presence of LPS genotype 7 in serogroup D.
Assuntos
Infecções por Pasteurella , Pasteurella multocida , Animais , Suínos , Pasteurella multocida/genética , Filogenia , Lipopolissacarídeos , Infecções por Pasteurella/veterinária , Fatores de Virulência/genéticaRESUMO
The misclassification of the species Pasteurella caecimuris Lagkouvardos et al. 2016 along with the heterotypic synonymy between P. caecimuris and Rodentibacter heylii Adhikary et al. 2017 has long been recognized. However, no formal assignment of P. caecimuris to its correct taxonomic position has been made accordingly and therefore the nomenclatural consequences have not been implemented. In the present study, the author first re-evaluates the taxonomic relationships of P. caecimuris using genome-based approaches, confirming the need of reclassification to the genus Rodentibacter and presenting evidence of the synonymy between R. heylii and P. caecimuris. Next, the author proposes a new name Rodentibacter caecimuris comb. nov. and, based on the priority of their specific epithets, treats Rodentibacter heylii as a later heterotypic synonym of Rodentibacter caecimuris.
Assuntos
Ácidos Graxos , Pasteurella , Pasteurellaceae , DNA Bacteriano/genética , Filogenia , RNA Ribossômico 16S/genética , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Composição de Bases , Ácidos Graxos/químicaRESUMO
Meningitis induced by Pasteurella multocida has been substantially described in clinical practice in both human and veterinary medicine, but the underlying mechanisms have not been previously reported. In this study, we investigated the influence of P. multocida infection on the permeability of the blood-brain barrier (BBB) using different models. Our in vivo tests in a mouse model and in vitro tests using human brain microvascular endothelial cell (hBMEC) model showed that P. multocida infection increased murine BBB permeability in mice and hBMEC monolayer permeability. Furthermore, we observed that P. multocida infection resulted in decreased expression of tight junctions (ZO1, claudin-5, occludin) and adherens junctions (E-cadherin) between neighboring hBMECs. Subsequent experiments revealed that P. multocida infection promoted the activation of hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) signaling and NF-κB signaling, and suppressed the HIF-1α/VEGFA significantly remitted the decrease in ZO1/E-cadherin induced by P. multocida infection (P < 0.001). NF-κB signaling was found to contribute to the production of chemokines such as TNF-1α, IL-ß, and IL-6. Additionally, transmission electron microscopy revealed that paracellular migration might be the strategy employed by P. multocida to cross the BBB. This study provides the first evidence of the migration strategy used by P. multocida to traverse the mammalian BBB. The data presented herein will contribute to a better understanding of the pathogenesis of the zoonotic pathogen P. multocida.
Assuntos
Junções Aderentes , Barreira Hematoencefálica , Células Endoteliais , Infecções por Pasteurella , Pasteurella multocida , Junções Íntimas , Animais , Pasteurella multocida/fisiologia , Barreira Hematoencefálica/microbiologia , Camundongos , Junções Aderentes/metabolismo , Infecções por Pasteurella/veterinária , Infecções por Pasteurella/microbiologia , Células Endoteliais/microbiologia , Células Endoteliais/fisiologia , Junções Íntimas/metabolismo , Humanos , Encéfalo/microbiologia , Encéfalo/irrigação sanguíneaRESUMO
Pasteurella multocida is an opportunistic zoonotic pathogen that primarily causes fatal respiratory diseases, such as pneumonia and respiratory syndromes. However, the precise mechanistic understanding of how P. multocida disrupts the epithelial barrier in mammalian lung remains largely unknown. In this study, using unbiased RNA-seq analysis, we found that the evolutionarily conserved Hippo-Yap pathway was dysregulated after P. multocida infection. Given the complexity of P. multocida infection associated with lung injury and systemic inflammatory processes, we employed a combination of cell culture models, mouse models, and rabbit models to investigate the dynamics of the Hippo-Yap pathway during P. multocida infection. Our findings reveal that P. multocida infection activates the Hippo-Yap pathway both in vitro and in vivo, by upregulating the upstream factors p-Mst1/2, p-Lats1, and p-Yap, and downregulating the downstream effectors Birc5, Cyr61, and Slug. Conversely, pharmacological inhibition of the Hippo pathway by XMU-MP-1 significantly rescued pulmonary epithelial cell apoptosis in vitro and reduced lung injury, systemic inflammation, and mouse mortality in vivo. Mechanistic studies revealed that P. multocida induced up-regulation of Rassf1 expression, and Rassf1 enhanced Hippo-Yap pathway through phosphorylation. Accordingly, in vitro knockdown of Rassf1 significantly enhanced Yap activity and expression of Yap downstream factors and reduced apoptosis during P. multocida infection. P. multocida-infected rabbit samples also showed overexpression of Rassf1, p-Lats1, and p-Yap, suggesting that P. multocida activates the Rassf1-Hippo-Yap pathway. These results elucidate the pathogenic role of the Rassf1-Hippo-Yap pathway in P. multocida infection and suggest that this pathway has the potential to be a drug target for the treatment of pasteurellosis.
Assuntos
Lesão Pulmonar , Pasteurella multocida , Doenças dos Roedores , Camundongos , Animais , Coelhos , Via de Sinalização Hippo , Transdução de Sinais , Lesão Pulmonar/veterinária , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Ciclo Celular/metabolismo , Pulmão/metabolismo , Apoptose , Proliferação de Células , MamíferosRESUMO
Pasteurella multocida is an important zoonotic respiratory pathogen capable of infecting a diverse range of hosts, including humans, farm animals, and wild animals. However, the precise mechanisms by which P. multocida compromises the pulmonary integrity of mammals and subsequently induces systemic infection remain largely unexplored. In this study, based on mouse and rabbit models, we found that P. multocida causes not only lung damage but also bacteremia due to the loss of lung integrity. Furthermore, we demonstrated that bacteremia is an important aspect of P. multocida pathogenesis, as evidenced by the observed multiorgan damage and systemic inflammation, and ultimately found that this systemic infection leads to a cytokine storm that can be mitigated by IL-6-neutralizing antibodies. As a result, we divided the pathogenesis of P. multocida into two phases: the pulmonary infection phase and the systemic infection phase. Based on unbiased RNA-seq data, we discovered that P. multocida-induced apoptosis leads to the loss of pulmonary epithelial integrity. These findings have been validated in both TC-1 murine lung epithelial cells and the lungs of model mice. Conversely, the administration of Ac-DEVD-CHO, an apoptosis inhibitor, effectively restored pulmonary epithelial integrity, significantly mitigated lung damage, inhibited bacteremia, attenuated the cytokine storm, and reduced mortality in mouse models. At the molecular level, we demonstrated that the FAK-AKT-FOXO1 axis is involved in P. multocida-induced lung epithelial cell apoptosis in both cells and animals. Thus, our research provides crucial information with regard to the pathogenesis of P. multocida as well as potential treatment options for this and other respiratory bacterial diseases.
Assuntos
Bacteriemia , Infecções por Pasteurella , Pasteurella multocida , Doenças dos Roedores , Humanos , Animais , Coelhos , Camundongos , Infecções por Pasteurella/veterinária , Infecções por Pasteurella/microbiologia , Proteínas Proto-Oncogênicas c-akt , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/veterinária , Pulmão/patologia , Bacteriemia/veterinária , Bacteriemia/patologia , Apoptose , Mamíferos , Proteína Forkhead Box O1RESUMO
BACKGROUND: Pasteurella multocida is a zoonotic pathogen that mainly causes local skin and soft tissue infections in the human body through cat and dog bites. It rarely causes bacteraemia (or sepsis) and meningitis. We reported a case of septic shock and meningitis caused by P. multocida in a patient without a history of cat and dog bites. CASE PRESENTATION: An 84-year-old male patient was urgently sent to the emergency department after he was found with unclear consciousness for 8 h, accompanied by limb tremors and urinary incontinence. In the subsequent examination, P. multocida was detected in the blood culture and wound secretion samples of the patient. However, it was not detected in the cerebrospinal fluid culture, but its DNA sequence was detected. Therefore, the patient was clearly diagnosed with septic shock and meningitis caused by P. multocida. The patient had no history of cat or dog contact or bite. The patient was subsequently treated with a combination of penicillin G, doxycycline, and ceftriaxone, and he was discharged after 35 days of hospitalisation. CONCLUSION: This report presented a rare case of septic shock and meningitis caused by P. multocida, which was not related to a cat or dog bite. Clinical doctors should consider P. multocida as a possible cause of sepsis or meningitis and should be aware of its potential seriousness even in the absence of animal bites.
Assuntos
Mordeduras e Picadas , Meningite , Infecções por Pasteurella , Pasteurella multocida , Choque Séptico , Masculino , Humanos , Animais , Cães , Gatos , Idoso de 80 Anos ou mais , Infecções por Pasteurella/diagnóstico , Infecções por Pasteurella/tratamento farmacológico , Choque Séptico/etiologia , Choque Séptico/complicações , Meningite/complicações , Mordeduras e Picadas/complicaçõesRESUMO
The avian influenza virus is an infectious agent that may cause global health problems in poultry and is potentially zoonotic. In the recent decades, bacterial-derived sialidases have been extensively studied for their ability to inhibit avian influenza virus infections. In this study, the antiviral activity of NanB sialidase from Pasteurella multocida was investigated through in vitro analysis using Madin-Darby canine kidney (MDCK) cells. NanB sialidase was purified from P. multocida to test its toxicity and its ability to hydrolyse its sialic acid receptors on MDCK cells. The H9N2 challenge virus was propagated in MDCK cells until cytopathic effects appeared. Antiviral activity of NanB sialidase was tested using MDCK cells, and then observed based on cell morphology, viral copy number, and expression of apoptosis-mediating genes. NanB sialidase effectively hydrolysed Neu5Acα(2,6)-Gal sialic acid at a dose of 129 mU/ml, while at 258 mU/ml, it caused toxicity to MDCK cells. Antiviral activity of sialidase was evident based on the significant decrease in viral copy number at all doses administered. The increase of p53 and caspase-3 expression was observed in infected cells without sialidase. Our study demonstrates the ability of NanB sialidase to inhibit H9N2 virus replication based on observations of sialic acid hydrolysis, reduction in viral copy number, and expression of apoptosis-related genes. The future application of sialidase may be considered as an antiviral strategy against avian influenza H9N2 virus infections. RESEARCH HIGHLIGHTSNanB sialidase effectively hydrolyses Neu5Acα(2,6)-Gal at a dose of 129 mU/ml.NanB sialidase from Pasteurella multocida can inhibit the entry of H9N2 virus into cells.NanB sialidase of Pasteurella multocida prevents infection-induced cell apoptosis.NanB sialidase reduces the H9N2 viral copy number in MDCK cells.
RESUMO
AIMS: This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant Pasteurella multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis. METHODS AND RESULTS: Danofloxacin at seven dosing regimens and 5 days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratios (AUC24h/MIC) of danofloxacin associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/mutant prevention concentration (MPC)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of three times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants. CONCLUSIONS: The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg-1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Fluoroquinolonas , Testes de Sensibilidade Microbiana , Pasteurella multocida , Pasteurella multocida/efeitos dos fármacos , Pasteurella multocida/genética , Fluoroquinolonas/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , MutaçãoRESUMO
Pasteurella multocida is an important bacterial pathogen that can cause diseases in both animals and humans. Its elevated morbidity and mortality rates in animals result in substantial economic repercussions within the livestock industry. The prevention of diseases caused by P. multocida through immunization is impeded by the absence of a safe and effective vaccine. Outer membrane vesicles (OMVs) secreted from the outer membrane of Gram-negative bacteria are spherical vesicular structures that encompass an array of periplasmic components in conjunction with a diverse assortment of lipids and proteins. These vesicles can induce antibacterial immune responses within the host. P. multocida has been shown to produce OMVs. Nonetheless, the precise characteristics and immunomodulatory functions of P. multocida OMVs have not been fully elucidated. In this study, OMVs were isolated from P. multocida using an ultrafiltration concentration technique, and their morphology, protein constitution, and immunomodulatory properties in RAW264.7 cells were studied. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) revealed that the OMVs exhibited typical spherical and bilayered lipid vesicular architecture, exhibiting an average diameter of approximately 147.5 nm. The yield of OMVs was 2.6 × 1011 particles/mL. Proteomic analysis revealed a high abundance of membrane-associated proteins within P. multocida OMVs, with the capability to instigate the host's immune response. Furthermore, OMVs stimulated the proliferation and cellular uptake of macrophages and triggered the secretion of cytokines, such as TNF-É, IL-1ß, IL-6, IL-10, and TGF-ß1. Consequently, our results indicated that OMVs from P. multocida could directly interact with macrophages and regulate their immune function in vitro. These results supported the prospective applicability of P. multocida OMVs as a platform in the context of vaccine development. KEY POINTS: ⢠Preparation and characterization of P. multocida OMVs. ⢠P. multocida OMVs possess a range of antigens and lipoproteins associated with the activation of the immune system. ⢠P. multocida OMVs can activate the proliferation, internalization, and cytokine secretion of macrophages in vitro.
Assuntos
Pasteurella multocida , Animais , Humanos , Estudos Prospectivos , Proteômica , Macrófagos , PeriplasmaRESUMO
Pasteurella multocida type A (PmA) mainly causes respiratory diseases such as pneumonia in bovines, leading to great economic losses to the breeding industry. At present, there is still no effective commercial vaccine against PmA infection. In this study, a mutant strain (PmCQ2Δ4555-4580) with brand-new phenotypes was obtained after serially passaging at 42 °C. Whole genome resequencing and PCR analysis showed that PmCQ2Δ4555-4580 missed six genes, including PmCQ2_004555, PmCQ2_004560, PmCQ2_004565, PmCQ2_004570, PmCQ2_004575, and PmCQ2_004580. Importantly, the virulence of PmCQ2Δ4555-4580 was reduced by approximately 2.8 × 109 times in mice. Notably, live PmCQ2Δ4555-4580 could provide 100%, 100% and 40% protection against PmA, PmB and PmF, respectively; and inactivated PmCQ2Δ4555-4580 could provide 100% and 87.5% protection against PmA and PmB. Interestingly, immune protection-related proteins were significantly upregulated in PmCQ2Δ4555-4580 based on RNA-seq and bioinformatics analysis. Meaningfully, by in vitro expression, purification and in vivo immunization, 12 proteins had different degrees of immune protective effects. Among them, PmCQ2_008205, PmCQ2_010435, PmCQ2_008190, and PmCQ2_004170 had the best protective effect, the protection rates against PmA were 50%, 40%, 30%, and 30%, respectively, and the protective rates against PmB were 62.5%, 42.9%, 37.5%, and 28.6%, respectively. Collectively, PmCQ2Δ4555-4580 is a potential vaccine candidate for the prevention of Pasteurellosis involving in high expression of immune protective related proteins.
Assuntos
Doenças dos Bovinos , Infecções por Pasteurella , Pasteurella multocida , Doenças dos Roedores , Animais , Camundongos , Bovinos , Pasteurella multocida/genética , Vacinas Atenuadas , Infecções por Pasteurella/prevenção & controle , Infecções por Pasteurella/veterinária , Imunização/veterinária , Vacinação/veterinária , Vacinas BacterianasRESUMO
Pasteurellosis is a common zoonotic infection that occurs after an animal bite or scratch (B/S). We compared the clinical features of six patients with non-B/S pasteurellosis with those of 14 patients with B/S infections. Pasteurella multocida was identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in all six non-B/S infections, whereas 13 of the 14 B/S infections were identified with diagnostic kits. The non-B/S infections were pneumonia (n = 3), skin and soft tissue infections (n = 2), and bacteremia (n = 1). Pneumonia occurred in two patients with underlying pulmonary disease, whereas ventilator-associated pneumonia developed in one patient with cerebral infarction. Pasteurella multocida was isolated from a blood specimen and nasal swab from a patient with liver cirrhosis (Child-Pugh class C) and diabetes. Cellulitis developed in one patient with diabetes and normal-pressure hydrocephalus, who had an open wound following a fall, and in one patient with diabetes and a foot ulcer. Three patients with non-B/S infections had no pet and no episode of recent animal contact. The rate of moderate-to-severe comorbidities was significantly higher in patients with non-B/S infections than in those with B/S infections (100% and 14.3%, respectively, p < 0.001). In conclusion, non-B/S infections can develop in patients with chronic pulmonary disease, invasive mechanical ventilation, or open wounds, or who are immunocompromised, irrespective of obvious animal exposure. In contrast to B/S infections, non-B/S pasteurellosis should be considered opportunistic.
Assuntos
Mordeduras e Picadas , Infecções por Pasteurella , Pasteurella multocida , Humanos , Infecções por Pasteurella/microbiologia , Infecções por Pasteurella/diagnóstico , Animais , Masculino , Feminino , Pasteurella multocida/isolamento & purificação , Pessoa de Meia-Idade , Idoso , Mordeduras e Picadas/complicações , Mordeduras e Picadas/microbiologia , Idoso de 80 Anos ou mais , Adulto , Bacteriemia/microbiologia , Bacteriemia/diagnósticoRESUMO
This study investigated the potential associations between 3 acute phase proteins (APP)-haptoglobin, serum amyloid A-and fibrinogen, clinical signs of respiratory disease, and the presence of bacterial pathogens in the lower respiratory tract (LRT) of preweaning dairy calves. This cross-sectional study included 150 preweaning calves (2-86 d old) from 15 large dairy herds in Estonia. Tracheobronchial lavage, blood, and fecal samples were collected from 5 calves showing clinical signs indicative of LRT disease, and samples from 5 calves without clinical signs of LRT disease per herd. All samples collected from these calves were analyzed for concentrations of systemic APP, LRT bacteria, and intestinal pathogens. Heifer blood and bulk tank milk samples were collected for the detection of disease-specific antibodies against bovine herpesvirus 1, bovine viral diarrhea virus, bovine respiratory syncytial virus, and Mycoplasma bovis. Mixed-effects linear regression models were used to analyze the associations of clinical respiratory disease signs and LRT bacteria with APP. Increased plasma fibrinogen concentrations in calves were associated with higher rectal temperature (>39.5°C), increased respiratory rate (>50 breaths/min), and coughing. Increased serum amyloid A concentrations were associated with higher rectal temperature (>39.5°C) and respiratory rate between 40 and 50 breaths/min. Calves with the presence of fecal Cryptosporidium spp. and rectal temperature of 39°C and above had increased serum haptoglobin concentrations. Increased fibrinogen concentrations were associated with the presence of Pasteurella multocida in the calf LRT, whereas increased concentrations of fibrinogen and serum amyloid A were associated with the presence of Trueperella pyogenes. In conclusion, APP showed variable associations with clinical signs of respiratory disease and LRT bacteria. Plasma fibrinogen concentration could be used as a complementary calf-side test to assess systemic inflammation caused by LRT bacteria such as Pasteurella multocida and Trueperella pyogenes in preweaning dairy calves.
Assuntos
Doenças dos Bovinos , Animais , Bovinos , Estudos Transversais , Doenças dos Bovinos/microbiologia , Doenças Respiratórias/veterinária , Doenças Respiratórias/microbiologia , Inflamação/veterinária , Estônia , Feminino , Fibrinogênio/análiseRESUMO
Two male Japanese Black calves developed an enlarged scrotum and testis. Orchiectomy was performed and pus was collected during surgery. After removal of the testis, bacteriological and histopathological examinations were conducted to investigate the cause and confirm the diagnosis. Based on the results obtained, both cases were diagnosed with epididymitis caused by an infection with Pasteurella multocida. This is the first study to show that P. multocida causes epididymitis in male calves. Further studies are required to clarify the details underlying the infection of calves with P. multocida.
Assuntos
Doenças dos Bovinos , Epididimite , Pasteurella multocida , Bovinos , Animais , Masculino , Epididimite/veterinária , TestículoRESUMO
Pasteurella multocida, a zoonotic pathogen that produces a 146-kDa modular toxin (PMT), causes progressive atrophic rhinitis with severe turbinate bone degradation in pigs. However, its mechanism of cytotoxicity remains unclear. In this study, we expressed PMT, purified it in a prokaryotic expression system, and found that it killed PK15 cells. The host factor CXCL8 was significantly upregulated among the differentially expressed genes in a transcriptome sequencing analysis and qPCR verification. We constructed a CXCL8-knockout cell line with a CRISPR/Cas9 system and found that CXCL8 knockout significantly increased resistance to PMT-induced cell apoptosis. CXCL8 knockout impaired the cleavage efficiency of apoptosis-related proteins, including Caspase3, Caspase8, and PARP1, as demonstrated with Western blot. In conclusion, these findings establish that CXCL8 facilitates PMT-induced PK15 cell death, which involves apoptotic pathways; this observation documents that CXCL8 plays a key role in PMT-induced PK15 cell death.