Review

Signal transduction in the mammalian cell during bacterial attachment and entry

Inflammasome signaling results in cell death and release of cytokines from the IL-1 family, which facilitates control over an infection. However, some pathogens such as Salmonella typhimurium (ST) activate various innate immune signaling pathways, including inflammasomes, yet evade these cell death mechanisms, resulting in a chronic infection. Here we investigated inflammasome signaling induced by acute and chronic isolates of ST obtained from different organs. We show that ST isolated from infected mice during the acute phase displays an increased potential to activate inflammasome signaling, which then undergoes a protracted decline during the chronic phase of infection. This decline in inflammasome signaling was associated with reduced expression of virulence factors, including flagella and the Salmonella pathogenicity island I genes. This reduction in cell death of macrophages induced by chronic isolates had the greatest impact on the NLRP3 inflammasome, which correlated with a reduction in caspase-1 activation. Furthermore, rapid cell death induced by Casp-1/11 by ST in macrophages limited the subsequent activation of cell death cascade proteins Casp-8, RipK1, RipK3, and MLKL to prevent the activation of alternative forms of cell death. We observed that the lack of the ability to induce cell death conferred a competitive fitness advantage to ST only during the acute phase of infection. Finally, we show that the chronic isolates displayed a significant attenuation in their ability to infect mice through the oral route. These results reveal that ST adapts during chronic infection by circumventing inflammasome recognition to promote the survival of both the host and the pathogen.

To cope with their continually fluctuating surroundings, pathovars of the unicellular phytopathogen Pseudomonas syringae have developed rapid and sophisticated signalling networks to sense extracellular stimuli, which allow them to adjust their cellular composition to survive and cause diseases in host plants. Comparative genomic analyses of P. syringae strains have identified various genes that encode several classes of signalling proteins, although how this bacterium directly perceives these environmental cues remains elusive. Recent work has revealed new mechanisms of a cluster of bacterial signal transduction systems that mainly include two-component systems (such as RhpRS, GacAS, CvsRS and AauRS), extracytoplasmic function sigma factors (such as HrpL and AlgU), nucleotide-based secondary messengers, methyl-accepting chemotaxis sensor proteins and several other intracellular surveillance systems. In this review, we compile a list of the signal transduction mechanisms that P. syringae uses to monitor and respond in a timely manner to intracellular and external conditions. Further understanding of these surveillance processes will provide new perspectives from which to combat P. syringae infections.

Microbial pathogenesis is a worldwide concern affecting millions of people around the world. These epidemics have caused thousands of deaths in the past. In the present chapter, we have tried to address the key issues regarding some important pathogens such as Mycobacterium tuberculosis, Yersinia pestis, Escherichia coli, Staphylococcus aureus, Vibrio cholerae, etc. and their infection and disease causing mechanism to the human host—strategies they use to overcome the antibiotics. We have provided insight into few genes and pathogenicity island which these organisms possess. Apart from the mechanism, the chapter describes evolution and how these organisms acquired the genes which they are using currently for pathogenesis. This chapter will also provide a brief insight into the vaccine development against some of these organisms with the methods used for the diagnosis and identification of pathogenic microbes related to medical and public health.

Previous studies have demonstrated that protein tyrosine phosphorylation plays an important role in WSSV infection. In the present work, in order to further elucidate the potential role of protein tyrosine phosphorylation in white spot syndrome virus (WSSV) infection. The expression variation of tyrosine phosphorylated proteins in hemocytes of shrimp (Litopenaeus vannamei) after WSSV infection were examined by flow cytometric immunofluorescence assay (FCIFA) and enzyme linked immunosorbent assay (ELISA), and results showed that the level of protein tyrosine phosphorylation in hemocytes fluctuated significantly after WSSV infection and exhibited two peaks at 6 and 24 h post infection (hpi). Meanwhile, tyrosine phosphorylated proteins in hemocytes after WSSV infection were also detected by cell immunofluorescence, and results showed that the fluorescence intensity in hemocytes was altered with the course of WSSV infection and showed stronger fluorescent signals at 6 and 24 hpi compared to other time points. Furthermore, two dimensional gel electrophoresis (2-DE) and 2-DE western blotting were applied to identify the differentially expressed tyrosine phosphorylated proteins in hemocytes before and after WSSV infection. The result of 2-DE western blotting showed that there were nine tyrosine phosphorylated proteins in the hemocytes of healthy shrimp, whereas twenty-one tyrosine phosphorylated proteins were detected in the hemocytes of shrimp at 6hpi. Then, the differential tyrosine phosphorylated proteins were analyzed by Mass Spectrometry (MS), and eight of them were identified to be sodium/potassium-transporting ATPase subunit alpha, ubiquitin/ribosomal L40 fusion protein, actin-D, phosphopyruvate hydratase, beta-actin, ATP synthase subunit beta, receptor for activated protein kinase c1 and protein disulfide-isomerase. Moreover, the expression levels of sodium/potassium-transporting ATPase subunit alpha, ubiquitin/ribosomal L40 fusion protein, phosphopyruvate hydratase, ATP synthase subunit beta, receptor for activated protein kinase c1 and protein disulfide-isomerase were examined to be up-regulated post WSSV infection by quantitative real-time RT-PCR. Taken together, these results demonstrated that protein tyrosine phosphorylation was involved in the process of WSSV infection, which might play an important role in the immune response to WSSV infection in shrimp.

Microbial pathogenesis is a worldwide concern affecting millions of people around the world. These epidemics have caused thousands of deaths in the past. In the present chapter, we have tried to address the key issues regarding some important pathogens such as Mycobacterium tuberculosis, Yersinia pestis, Escherichia coli, Staphylococcus aureus, Vibrio cholerae, etc. and their infection and disease causing mechanism to the human host—strategies they use to overcome the antibiotics. We have provided insight into few genes and pathogenicity island which these organisms possess. Apart from the mechanism, the chapter describes evolution and how these organisms acquired the genes which they are using currently for pathogenesis. This chapter will also provide a brief insight into the vaccine development against some of these organisms with the methods used for the diagnosis and identification of pathogenic microbes related to medical and public health.

The aim of this study was to evaluate Ca²⁺ ATPase activity and the lipid peroxidation in muscles from rats experimentally infected by Trypanosoma evansi and its roles in the muscle pathogenesis in trypanosomosis. Thirty-six rats were divided in two groups. Group A was infected with an isolate from T. evansi and group B was used as a negative control. Group A was divided into three subgroups (A1, A2 and A3), three animals each group, as well as group B (B1, B2 and B3). The collection of samples were performed at days 5 (A1 and B1), 15 (A2 and B2) and 30 (A3 and B3) post-infection (PI) with the purpose of comparison between healthy and infected rats in the course of the disease. The Ca²⁺ ATPase enzyme activity was determined in skeletal muscle samples. Muscle tissue lipid peroxidation was determined by TBARS levels, and histopathologically it was investigated a possible damage to the muscle tissue of rats infected with T. evansi. It was observed a significant decrease of Ca²⁺ ATPase activity in infected rats compared to not-infected. This enzymatic inhibition was observed at days 5, 15 and 30 PI. A significant increase was observed for TBARS levels in the muscles of infected rats at days 5, 15 and 30 PI. It was not identified any histological alterations for gastrocnemius in rats infected by T. evansi at days 5 and 15 PI. Nevertheless, at day 30 PI it was verified inflammatory infiltrate with mononuclear cells between muscle fibers in three infected rats (50%). T. evansi infections in rats showed a negative correlation between Ca²⁺ ATPase and TBARS levels. Based on these results we suggest that the leg weakness and muscle injuries common in infected animals with T. evansi may be related to a reduced activity of Ca²⁺ ATPase and oxidative stress.