An anti-Shiga toxin VHH nanobody multimer protects mice against fatal toxicosis when administered intramuscularly as repRNA.

Hemolytic uremic syndrome (HUS) is a systemic sequelae from gastrointestinal infection with Shiga toxin (Stx) producing (STEC) that can result in acute kidney injury, lasting renal disease, and death. Despite a window for intervention between hemorrhagic diarrhea and onset of HUS, no specific therapies exist to prevent or treat HUS following STEC infection. Furthermore, there is no way to predict which patients with STEC will develop HUS or any rapid way to determine which Stx variant is present.

PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections.

Virulent infectious agents such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and methicillin-resistant (MRSA) induce tissue damage that recruits neutrophils, monocyte, and macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes, and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2-infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage, and cytokine storm.

Systems genetics uncover new loci containing functional gene candidates in Mycobacterium tuberculosis-infected Diversity Outbred mice.

Mycobacterium tuberculosis infects two billion people across the globe, and results in 8-9 million new tuberculosis (TB) cases and 1-1.5 million deaths each year. Most patients have no known genetic basis that predisposes them to disease.

infection of human small intestinal epithelial cells induces type III interferon and impairs infectivity of Rotavirus.

Cryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogen and absence of in vitro growth platforms has limited our understanding of host-pathogen interactions and development of effective treatments. To address this problem, we developed a stem cell-derived culture system for using human enterocytes differentiated under air-liquid interface (ALI) conditions.

infection of human small intestinal epithelial cells induces type III interferon and impairs infectivity of Rotavirus.

Cryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogen and absence of in vitro growth platforms has limited our understanding of host-pathogen interactions and development of effective treatments. To address this problem, we developed a stem cell-derived culture system for using human enterocytes differentiated under air-liquid interface (ALI) conditions.

A highly antigenic fragment within the zoonotic Cryptosporidium parvum Gp900 glycoprotein (Domain 3) is absent in human restricted Cryptosporidium species.

We identified a fragment (Domain 3-D3) of the immunodominant sporozoite surface glycoprotein of the zoonotic parasite Cryptosporidium gp900, which is absent C. hominis and C. parvum anthroponosum.

Development of Two Mouse Models for Vaccine Evaluation against Cryptosporidiosis.

Cryptosporidiosis was shown a decade ago to be a major contributor to morbidity and mortality of diarrheal disease in children in low-income countries. A serious obstacle to develop and evaluate immunogens and vaccines to control this disease is the lack of well-characterized immunocompetent rodent models. Here, we optimized and compared two mouse models for the evaluation of vaccines: the Cryptosporidium tyzzeri model, which is convenient for screening large numbers of potential mixtures of immunogens, and the Cryptosporidium parvum-infected mouse pretreated with interferon gamma-neutralizing monoclonal antibody.

Reduced SARS-CoV-2 disease outcomes in Syrian hamsters receiving immune sera: Quantitative image analysis in pathologic assessments.

There is a need to standardize pathologic endpoints in animal models of SARS-CoV-2 infection to help benchmark study quality, improve cross-institutional comparison of data, and assess therapeutic efficacy so that potential drugs and vaccines for SARS-CoV-2 can rapidly advance. The Syrian hamster model is a tractable small animal model for COVID-19 that models clinical disease in humans. Using the hamster model, the authors used traditional pathologic assessment with quantitative image analysis to assess disease outcomes in hamsters administered polyclonal immune sera from previously challenged rhesus macaques.

The repurposing of Tebipenem pivoxil as alternative therapy for severe gastrointestinal infections caused by extensively drug-resistant spp.

Background: Diarrhoea remains one of the leading causes of childhood mortality globally. Recent epidemiological studies conducted in low-middle income countries (LMICs) identified spp. as the first and second most predominant agent of dysentery and moderate diarrhoea, respectively.

An immunocompetent rat model of infection with Cryptosporidium hominis and Cryptosporidium parvum.

A major obstacle to developing vaccines against cryptosporidiosis, a serious diarrheal disease of children in developing countries, is the lack of rodent models essential to identify and screen protective immunogens. Rodent models commonly used for drug discovery are unsuitable for vaccine development because they either are purposefully immunodeficient or immunosuppressed. Here, we describe the development and optimization of an immunocompetent intratracheal (IT) rat model susceptible to infections with sporozoites of Cryptosporidium parvum and Cryptosporidium hominis - the primary causes of human cryptosporidiosis.

A Pasteurella multocida strain affecting nulliparous heifers and calves in different ways.

Pasteurella multocida isolates from dairy cattle on a farm in Spain were associated with pneumonia of calves (six isolates) and mastitis of heifers (five isolates). The objective was to determine if the P. multocida isolates retrieved from both disease scenarios were the same strain or whether more than one strain was present.

Whole Genome Sequence Analysis of Pig Respiratory Bacterial Pathogens with Elevated Minimum Inhibitory Concentrations for Macrolides.

Macrolides are often used to treat and control bacterial pathogens causing respiratory disease in pigs. This study analyzed the whole genome sequences of one clinical isolate of Actinobacillus pleuropneumoniae, Haemophilus parasuis, Pasteurella multocida, and Bordetella bronchiseptica, all isolated from Australian pigs to identify the mechanism underlying the elevated minimum inhibitory concentrations (MICs) for erythromycin, tilmicosin, or tulathromycin. The H.

Variation in the Antimicrobial Susceptibility of Actinobacillus pleuropneumoniae Isolates in a Pig, Within a Batch of Pigs, and Among Batches of Pigs from One Farm.

Antimicrobial resistance in bacterial porcine respiratory pathogens has been shown to exist in many countries. However, little is known about the variability in antimicrobial susceptibility within a population of a single bacterial respiratory pathogen on a pig farm. This study examined the antimicrobial susceptibility of Actinobacillus pleuropneumoniae using multiple isolates within a pig and across the pigs in three different slaughter batches.

Use of a proposed antimicrobial susceptibility testing method for Haemophilus parasuis.

The aim of this study was to examine the antimicrobial susceptibility of 97 Haemophilus parasuis cultured from Australian pigs. As there is no existing standard antimicrobial susceptibility technique available for H. parasuis, methods utilising the supplemented media, BA/SN for disc diffusion and test medium broth (TMB) for a microdilution technique, were initially evaluated with the reference strains recommended by the Clinical and Laboratory Standards Institute.

Antimicrobial resistance in bacteria associated with porcine respiratory disease in Australia.

The porcine respiratory disease complex greatly affects the health and production of pigs. While antimicrobial agents are used to treat the respiratory infections caused by bacterial pathogens, there is no current information on antimicrobial resistance in Australian pig respiratory bacterial isolates. The aim of this study was to determine the antimicrobial resistance profiles, by determining the minimum inhibitory concentration of nine antimicrobial agents for 71 Actinobacillus pleuropneumoniae, 51 Pasteurella multocida and 18 Bordetella bronchiseptica cultured from Australian pigs.