Salmonella - foodborne pathogen and antimicrobial resistance

Foodborne diseases encompass a wide spectrum of illnesses and are a growing public health problem worldwide. They are caused by consumption of food or water contaminated by pathogenic (disease-causing) microorganisms such as bacteria, viruses and parasites. The contamination of food can occur at any stage in the process from food production to consumption (“farm to fork”) and can result from environmental contamination (water, soil or air). They enter the body through the gastrointestinal tract where the first symptoms often occur like nausea, vomiting, stomach cramps, and diarrhoea. However, symptoms differ among the different types of foodborne diseases and the patient’s immune status. Symptoms can sometimes be severe and some foodborne illnesses can even be fatal. Commonly recognized foodborne infections are: campylobacteriosis, Escherichia coli O157:H7 infection and haemolytic uremic syndrome (HUS), salmonellosis, cryptosporidiosis, listeriosis, giardiasis. norovirus infection, scombroid fish poisoning, shigellosis, toxoplasmosis, Vibrio infection and yersiniosis. One of the top three germs that cause illnesses from food eaten in EU is Salmonella.

Characterization of the role of yadK in the pathogenesis of enterohaemorrhagic E. coli O157:H7

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 can use serious diarrhea and haemolytic uremic syndrome. Various factors including adhesins contribute to pathogenesis of EHEC. Previous studies suggested that yadK gene, which encodes a putative fimbrial adhesin in EHEC, may be involved in response of EHEC to acid stress. To characterize role of yadK protein in the pathogenesis of EHEC, recombinant yadK protein was generated and used to immunize rabbit to obtain anti-yadK antiserum, which was able to specifically recognize over-expressed yadK protein in EHEC. Western blotting with anti-yadK revealed a higher level of yadK expression in EHEC under acid adapted-acid stress compared to EHEC under unstressed conditions, which confirmed earlier yadK mRNA studies and indicated that yadK is upregulated in EHEC under acid stress. Finally, we observed that anti-yadK antiserum was able to specifically reduce adhesion of acid stressed EHEC to human epithelial cells compared to adhesion level of unstressed EHEC.

Characterization of the role of yadK in the pathogenesis of enterohaemorrhagic E. coli O157:H7

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 can use serious diarrhea and haemolytic uremic syndrome. Various factors including adhesins contribute to pathogenesis of EHEC. Previous studies suggested that yadK gene, which encodes a putative fimbrial adhesin in EHEC, may be involved in response of EHEC to acid stress. To characterize role of yadK protein in the pathogenesis of EHEC, recombinant yadK protein was generated and used to immunize rabbit to obtain anti-yadK antiserum, which was able to specifically recognize over-expressed yadK protein in EHEC. Western blotting with anti-yadK revealed a higher level of yadK expression in EHEC under acid adapted-acid stress compared to EHEC under unstressed conditions, which confirmed earlier yadK mRNA studies and indicated that yadK is upregulated in EHEC under acid stress. Finally, we observed that anti-yadK antiserum was able to specifically reduce adhesion of acid stressed EHEC to human epithelial cells compared to adhesion level of unstressed EHEC.

Eculizumab therapy on a patient with co‐existent lupus nephritis and C3 mutation‐related atypical haemolytic uremic syndrome: a case report

Background Thrombotic microangiopathy (TMA), a rare but serious complication of systemic lupus erythematosus (SLE), is associated with poor outcomes to conventional immunosuppressive therapy. Recently, eculizumab, a humanised monoclonal antibody that blocks the complement factor 5, has been known to effectively treat atypical haemolytic uremic syndrome (aHUS). Here, we report a case of aHUS co-existing with lupus nephritis that was successfully treated with eculizumab. Case presentation A 23-year-old man presented with abdominal pain and diarrhoea. Initial laboratory tests have shown thrombocytopaenia, microangiopathic haemolytic anaemia, and acute kidney injury. Immunologic tests were consistent with SLE. Kidney biopsy have revealed lupus nephritis class IV-G with TMA. Genetic analysis have shown complement C3 gene mutations, which hints the co-existence of lupus nephritis with aHUS, a form of complement-mediated TMA. Although initial treatment with haemodialysis, plasma exchange, and conventional immunosuppressive therapy (steroid and cyclophosphamide) did not appreciably improve kidney function and thrombocytopaenia, the patient was able to respond to eculizumab therapy. Conclusions Due to the similar features of TMA and SLE, clinical suspicion of aHUS in patients with lupus nephritis is important for early diagnosis and prompt management. Timely administration of eculizumab should be considered as a treatment option for aHUS in lupus nephritis patients to yield optimal therapeutic outcomes.

Transplant-associated Thrombotic Microangiopathy Treated with Eculizumab and Romiplostim

Transplant-associated thrombotic microangiopathy (TA-TMA) can occur after solid organ transplantation. It results in thrombocytopenia, haemolytic anaemia and microvascular occlusion. TA-TMA is not fully understood and treatment has not been clearly established. However, there is increasing evidence to suggest an immune-complement mediated component to its development. Eculizumab is a monoclonal antibody that inhibits the cleavage of C5 into pro-inflammatory, prothrombotic terminal complement elements and has been utilized in the treatment of atypical haemolytic uremic syndrome. We report a case of TA-TMA successfully treated with eculizumab and romiplostim. This case adds to the evidence that TA-TMA is triggered by complement dysregulation and suggests possible interventions for refractory cases.