-
Tropical Medicine and Infectious Disease Oct 2023is a major foodborne pathogen of both animals and humans. This bacterium is responsible for considerable morbidity and mortality world-wide. Different serovars of this... (Review)
Review
is a major foodborne pathogen of both animals and humans. This bacterium is responsible for considerable morbidity and mortality world-wide. Different serovars of this genus cause diseases ranging from self-limiting gastroenteritis to a potentially fatal systemic disease known as enteric fever. Gastrointestinal infections with are usually self-limiting and rarely require medical intervention. Bloodstream infections, on the other hand, are often fatal even with hospitalization. This review describes the routes and underlying mechanisms of the extraintestinal dissemination of and the chronic infections that sometimes result. It includes information on the pathogenicity islands and individual virulence factors involved in systemic dissemination as well as a discussion of the host factors that mediate susceptibility. Also, the major outbreaks of invasive disease in the tropics are described.
PubMed: 37999606
DOI: 10.3390/tropicalmed8110487 -
Nature Microbiology Oct 2023Cell-intrinsic defences constitute the first line of defence against intracellular pathogens. The guanosine triphosphatase RAB32 orchestrates one such defence response...
Cell-intrinsic defences constitute the first line of defence against intracellular pathogens. The guanosine triphosphatase RAB32 orchestrates one such defence response against the bacterial pathogen Salmonella, through delivery of antimicrobial itaconate. Here we show that the Parkinson's disease-associated leucine-rich repeat kinase 2 (LRRK2) orchestrates this defence response by scaffolding a complex between RAB32 and aconitate decarboxylase 1, which synthesizes itaconate from mitochondrial precursors. Itaconate delivery to Salmonella-containing vacuoles was impaired and Salmonella replication increased in LRRK2-deficient cells. Loss of LRRK2 also restored virulence of a Salmonella mutant defective in neutralizing this RAB32-dependent host defence pathway in mice. Cryo-electron tomography revealed tether formation between Salmonella-containing vacuoles and host mitochondria upon Salmonella infection, which was significantly impaired in LRRK2-deficient cells. This positions LRRK2 centrally within a host defence mechanism, which may have favoured selection of a common familial Parkinson's disease mutant allele in the human population.
Topics: Humans; Mice; Animals; Parkinson Disease; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Salmonella Infections; Salmonella
PubMed: 37640963
DOI: 10.1038/s41564-023-01459-y -
Pharmacological Reports : PR Aug 2023Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for the treatment of non-erosive reflux disease (NERD), ulcers associated with non-steroidal... (Review)
Review
Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for the treatment of non-erosive reflux disease (NERD), ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs), esophagitis, peptic ulcer disease (PUD), Zollinger-Ellison syndrome (ZES), gastroesophageal reflux disease (GERD), non-ulcer dyspepsia, and Helicobacter pylori eradication therapy. The drugs have the effect of inhibiting acid production in the stomach. According to research, PPIs can affect the composition of gut microbiota and modulate the immune response. Recently, there has been a problem with the over-prescription of such drugs. Although PPIs do not have many side effects, their long-term use can contribute to small intestinal bacterial overgrowth (SIBO) or C. difficile and other intestinal infections. Probiotic supplementation during PPIs therapy may provide some hope in the reduction of emerging therapy side effects. This review aims to present the most important effects of long-term PPI use and provides critical insights into the role of probiotic intervention in PPI therapy.
Topics: Humans; Proton Pump Inhibitors; Clostridioides difficile; Dysbiosis; Gastroesophageal Reflux; Probiotics; Immunity; Immunomodulation
PubMed: 37142877
DOI: 10.1007/s43440-023-00489-x -
Microbiological Research Oct 2023Inflammasome activation is a critical defense mechanism against bacterial infection. Previous studies suggest that inflammasome activation protects against Salmonella...
Inflammasome activation is a critical defense mechanism against bacterial infection. Previous studies suggest that inflammasome activation protects against Salmonella oral infection. Here we find inflammasome activation plays a critical role in the pathogenesis of Salmonella systemic infection. We show that in a systemic infection model by i.p. injection of Salmonella, deficiency of caspase-1 or gasdermin-D prolonged survival time, reduced plasma concentrations of the proinflammatory cytokines IL-1β, IL-6 and TNFα. These deficiencies also protected against coagulopathy during Salmonella infection as evidenced by diminished prolongation of prothrombin time and increase in plasma thrombin-antithrombin complex concentrations in the caspase-1 or gasdermin-D deficient mice. Activation of the NAIP/NLRC4 inflammasome by flagellin and/or the components of the SPI1 type 3 secretion system played a critical role in Salmonella-induced coagulopathy. In the absence of flagellin and SPI1, the Salmonella mutant strain still triggered coagulopathy through the caspase-11/NLRP3 pathway. Our results reveal a previously undisclosed role of the inflammasomes and pyroptosis in the pathogenesis of Salmonella systemic infection.
Topics: Mice; Animals; Inflammasomes; Pyroptosis; Flagellin; Calcium-Binding Proteins; Apoptosis Regulatory Proteins; Gasdermins; Caspases; Salmonella typhimurium; Caspase 1; Salmonella Infections; Inflammation
PubMed: 37467711
DOI: 10.1016/j.micres.2023.127460 -
Microorganisms Nov 2023is the leading cause of food-borne zoonotic disease worldwide. Non-typhoidal serotypes are the primary etiological agents associated with salmonellosis in poultry.... (Review)
Review
is the leading cause of food-borne zoonotic disease worldwide. Non-typhoidal serotypes are the primary etiological agents associated with salmonellosis in poultry. Contaminated poultry eggs and meat products are the major sources of human infection. Horizontal and vertical transmission are the primary routes of infection in chickens. The principal virulence genes linked to pathogenesis in poultry are located in pathogenicity islands 1 and 2 (SPI-1 and SPI-2). Cell-mediated and humoral immune responses are involved in the defense against invasion in poultry. Vaccination of chickens and supplementation of feed additives like prebiotics, probiotics, postbiotics, synbiotics, and bacteriophages are currently being used to mitigate the load in poultry. Despite the existence of various control measures, there is still a need for a broad, safe, and well-defined strategy that can confer long-term protection from in poultry flocks. This review examines the current knowledge on the etiology, transmission, cell wall structure, nomenclature, pathogenesis, immune response, and efficacy of preventative approaches to .
PubMed: 38004824
DOI: 10.3390/microorganisms11112814 -
Pathogens (Basel, Switzerland) Oct 2023is one of the most spread foodborne pathogens worldwide, and infections in humans still represent a global health burden. The main source of infections in humans is... (Review)
Review
is one of the most spread foodborne pathogens worldwide, and infections in humans still represent a global health burden. The main source of infections in humans is represented by contaminated animal-derived foodstuffs, with pork products being one of the most important players. infection in swine is critical not only because it is one of the main causes of economic losses in the pork industry, but also because pigs can be infected by several serovars, potentially contaminating the pig meat production chain and thus posing a significant threat to public health globally. As of now, in Europe and in the United States, swine-related serovars, e.g., Typhimurium and its monophasic variant subsp. 1,4,[5],12:i:-, are also frequently associated with human salmonellosis cases. Moreover, multiple outbreaks have been reported in the last few decades which were triggered by the consumption of -contaminated pig meat. Throughout the years, changes and evolution across the pork industry may have acted as triggers for new issues and obstacles hindering control along the food chain. Gathered evidence reinforces the importance of coordinating control measures and harmonizing monitoring programs for the efficient control of in swine. This is necessary in order to manage outbreaks of clinical disease in pigs and also to protect pork consumers by controlling subclinical carriage and shedding. This review provides an update on infection in pigs, with insights on ecology, focusing mainly on Choleraesuis, . Typhimurium, and . 1,4,[5],12:i:-, and their correlation to human salmonellosis cases. An update on surveillance methods for epidemiological purposes of infection in pigs and humans, in a "One Health" approach, will also be reported.
PubMed: 37887782
DOI: 10.3390/pathogens12101267