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Molecular genetics of salmonela survival and resistance
Salmonella is one of the most common cause of the food borne illness. Salmonella belongs to Enterobacteriacae family and consists of 2 species, which diverge on 6 subspecies.These subspecies consists of 2700 serovars. There are typhoid serovars among them - S. Typhi, Paratyphi A, B, C - which cause typhoid fever in human. The rest of the serovars are non-typhoidal and leads to gastroenteritis both in animal and human. Salmonella enters to a mammal organism as a result of consumption of contaminated food products: meat, eggs, milk and products containing them. The entry of the infection for salmonellosis is the small intestine mucosa. Salmonella attaches to cell walls by fimbria and pili.
Salmonella has several systems that are activated in response to adverse conditions such as: high osmolarity, acid or heat shock and nutrient deficiencies. They are based on the principle of a two-component system in which there is a sensor that receives cytoplasmic signals, and a regulator. Regulator (usually DNA-binding protein) initiates the transcription of the virulence genes (Chakraborty, 2015). The sensor is histidine kinase, which phosphorylates the regulatory protein, thereby activating it.During the infectious cycle of salmonella in mammalian organism the formation of specific vacuole SCV takes place (Salmonella-containing vacuole-containing vacuole containing salmonella) in the cytoplasm of the eukaryotic cell (Steele-Mortimer, 2008). SCV is a modified phagosome, which is formed as a result of cytoskeleton rearrangements. The target are usually phagocytic cells : neutrophils, macrophages and epithelial cells of the small intestine mucosa - M-cells (Akhmetova, 2012).
Given the specific mechanism of infection, salmonella is considered a facultative intracellular pathogen. Bacterium invades the eukaryotic cell by rearrangement of its cytoskeleton with effector proteins and continue to persistence in a form of SCV.
It is well-known nowadays that tolerance to high osmotic pressure is achieved through the EnvZ / OmpR system, which also regulates the expression of the ssrAB operon that is localized on the Salmonella pathogenicity island SPI-2 and triggers the expression of the effector proteins. The ssrAB operon is also regulated by the two-component acid shock response system PhoP / PhoQ (Worley, 2000). The functioning of the PhoP / PhoQ system directly depends on the sigma factor RpoS, which accumulates under low concentrations of magnesium cations (Tu, 2006).
According to the researches of transduction between the EnvZ / OmpR components, it is clear that salmonella receives signals from the cytoplasmic environment, and sensory molecules are located on the inner membrane (Kenney, 2019; Wang et al., 2012).
The ability to survive under acid shock is provided by the PhoP / PhoQ system, which also operates on the principle of signal transduction. PhoQ is a Histidine Kinase Signal Sensor. Signals are acidic pH, divalent cations and positively charged antimicrobial peptides.
An important function of the two-component PhoP / PhoQ system is the control of spi ssa gene expression in a macrophage environment (Bijlsma, 2005). These genes are the main component of the type III secretion systems and are transcribed only when salmonella enters eukaryotic cell. (Bijlsma, 2005). The main regulator of signal transduction systems PhoP/PhoQ and EnvZ/OmpR is sigma-factor RpoS - subunit of bacterial RNA-polymerase - which operates in stationary phase at low pH, high omolarity, heat shock or nutrient deficiency. RpoS protein accumulates in adverse conditions during stationary phase (Mg2+ deficiency, low pH, high osmolarity). Need in magnesium cations is dependent on their ability to act as cofactors in many enzymatic activities. The accumulation begins at exponential (logarithmic) phase of bacterial reproduction. This is the phase of active cell division. Two factors MgtA and MgtB are responsible for Mg2+ transport. Another molecule with the same function is CorA - bivalent cation channel, though its transcriptions doesn’t depent on magnesium concentration in cell. In a case of magnesium deficiency at the stationary phase, RpoS accumulates vigorously an initiates replication of PhoP/PhoQ.
PhoP/PhoQ regulates tolerance to inorganic acids. Also, PhoP/PhoQ controls adaptation to magnesium cations deficiency and macrophage activity. Results of many studies on genes coding this system and their mutations led to conclusion the mutation or inactivation of one factor causes decrease in virulence and makes bacterial susceptible to acid environment.
To date, the stages of the infectious process for salmonellosis have been studied and described in detail in the literature. Particular attention is paid to signal transduction systems that are common among enterobacteria and help to avoid adverse conditions. Their functioning and regulation are investigated.
It is known that salmonella receives signals for the activation of sensors from the cytoplasm, but the nature of these signals is not yet fully understood. Adaptation of the bacteria to adverse conditions and the response to phagocytosis is initiated by the transcription of pathogenic genes and the suppression of the transcription of the operon, which neutralize the conditions in the cytoplasm of salmonella cells. Thus, adapting to the conditions of target cells, salmonella continues to multiply in the body.
Key words: salmonella, pH, osmolarity, virulencegenes, operon, signal transduction.
1. Grimont Patrick, A.D., François-Xavier, Weill. Antigenic formulae of the Salmonella serovars. WHO collaborating centre for reference and research on Salmonella. 2007, 9, pp. 1–166.
2. McClelland, Michael. Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid. Nature genetics. 2004, 36, 12, 1268 p.
3. Kidgell, Claire. Salmonella typhi, the causative agent of typhoid fever, is approximately 50,000 years old. Infection, Genetics and Evolution. 2002, 2.1, pp. 39–45.
4. Shyrobokov, V.P. (2010). Medychna mikrobiologija, virusologija ta imunologija. [Medical Microbiology, Virology and Immunology].
5. Finn, Ciaran E. A second wave of Salmonella T3SS1 activity prolongs the lifespan of infected epithelial cells. PLoS pathogens. 2017, 13.4, e1006354.
6. Srikanth, C.V. Salmonella effector proteins and host-cell responses. Cellular and Molecular Life Sciences. 2011, 68.22, 3687p.
7. Kenney Linda, J. The role of acid stress in Salmonella pathogenesis. Current opinion in microbiology. 2019, 47, pp. 45–51.
8. Chakraborty, Smarajit., Hideaki, Mizusaki., Linda J. Kenney. A FRET-based DNA biosensor tracks OmpR-dependent acidification of Salmonella during macrophage infection. PLoS biology. 2015, 13.4, e1002116.
9. Richardson, Lauren A. How salmonella survives the macrophage’s acid. attack. PLoS biology. 2015, 13.4, e1002117.
10. Rathman, Michelle., Michael D. Sjaastad., Stanley, Falkow. Acidification of phagosomes containing Salmonella typhimurium in murine macrophages. Infection and immunity. 1996, 64.7, pp. 2765–2773.
11. Densen, P., Clark, R. A., Nauseef, W. M. Granulocytic phagocytes, In. G. L. Mandell, R. G. Douglas, and J. E. Bennett (ed.), Principles and practice of infectious diseases, 3rd ed., vol. 1. Churchill Livingstone, New York. 1990, p. 78–101.
12. Fridovich, I. The biology of oxygen radicals. Science. 1978, 201, pp. 875–800.
13. Coffey, J. W., Duve, C. D. Digestive activity of lysosomes. I. The digestion of proteins by extracts of rat liver lysosomes. J. Biol. Chem. 1968, 243, pp. 3255–3263.
14. Steele-Mortimer, Olivia. The Salmonella-containing vacuole—moving with the times. Current opinion in microbiology. 11.1, 2008, pp. 38–45.
15. Ahmetova, D.G. Sal'monelly: molekuljarnye mehanizmy prisposoblennosti i factory virulentnosti. Eurasian Journal of Applied Biotechnology. [Salmonella: molecular fitness mechanisms and virulence factors]. 2012, 1, pp. 3–24.
16. Worley Micah, J., Katherine, H.L. Ching., Fred, Heffron. Salmonella SsrB activates a global regulon of horizontally acquired genes. Molecular microbiology. 2000, 36.3, pp. 749–761.
17. Tu, Xuanlin. The PhoP/PhoQ two-component system stabilizes the alternative sigma factor RpoS in Salmonella enteric. Proceedings of the National Academy of Sciences. 2006, 103.36, pp. 13503–13508.
18. Zhang, Ying. Reciprocal Regulation of OmpR and Hfq and Their Regulatory Actions on the Vi Polysaccharide Capsular Antigen in Salmonella enterica Serovar Typhi. Current microbiology. 2018, 75.6, pp. 773–778.
19. Bang, Iel Soo. OmpR regulates the stationary-phase acid tolerance response of Salmonella enterica serovar Typhimurium. Journal of bacteriology. 2000, 182.8, pp. 2245–2252.
20. Bang, Iel Soo. Autoinduction of the ompR response regulator by acid shock and control of the Salmonella enterica acid tolerance response. Molecular microbiology. 2002, 44.5, pp. 1235–1250.
21. Wang., Loo Chien. The inner membrane histidine kinase EnvZ senses osmolality via helix‐coil transitions in the cytoplasm. The EMBO journal. 2012, 31.11, pp. 2648–2659.
22. Shi, Yixin. Transcriptional control of the antimicrobial peptide resistance ugtL gene by the Salmonella PhoP and SlyA regulatory proteins. Journal of Biological Chemistry. 2004, 279.37, pp. 38618–38625.
23. Kato, Akinori., Eduardo A. Groisman. The PhoQ/PhoP regulatory network of Salmonella enterica. Bacterial Signal Transduction. Networks and Drug Targets. Springer. New York. NY. 2008, pp. 7–21.
24. Bijlsma Jetta, J.E., Eduardo, A. Groisman. The PhoP/PhoQ system controls the intramacrophage type three secretion system of Salmonella enterica. Molecular microbiology. 2005, 57.1, pp. 85–96.
25. Cirillo, Daniela Maria. Macrophage‐dependent induction of the Salmonella pathogenicity island 2 type III secretion system and its role in intracellular survival. Molecular microbiology. 1998, 30.1, pp. 175–188.
26. Ratner Dmitry, M., Pontus A. Orning., Egil, Lien. Bacterial secretion systems and regulation of inflammasome activation. Journal of leukocyte biology. 2017, 101.1, pp. 165–181.
27. Robbe-Saule., Véronique. Physiological effects of Crl in Salmonella are modulated by σS level and promoter specificity. Journal of bacteriology. 2007, 189.8, pp. 2976–2987.
28. Park, Myungseo. ATP reduction by MgtC and Mg2+ homeostasis by MgtA and MgtB enables Salmonella to accumulate RpoS upon low cytoplasmic Mg2+ stress. Molecular microbiology. 2018, 110.2, pp. 283–295.
29. Snavely, M.D. Magnesium transport in Salmonella typhimurium. Regulation of mgtA and mgtB expression. Journal of Biological Chemistry. 1991, 266.2, pp. 824–829.
30. Choi, Eunna. Elongation factor P controls translation of the mgtA gene encoding a Mg2+ transporter during Salmonella infection. Microbiology Open. 2018, e00680.
31. Kowatz, Thomas., Michael E. Maguire. Loss of cytosolic Mg2+ binding sites in the Thermotoga maritima CorA Mg2+ channel is not sufficient for channel opening. Biochimica et Biophysica Acta (BBA)-General Subjects. 2019, 1863.1, pp. 25–30.
32. Hmiel, S.P. Magnesium transport in Salmonella typhimurium: characterization of magnesium influx and cloning of a transport gene. Journal of bacteriology. 1986, 168.3, pp. 1444–1450.
33. Gall Aaron, R. High‐level, constitutive expression of the mgtC gene confers increased thermotolerance on Salmonella enterica serovar Typhimurium. Molecular microbiology. 2018.
34. Papp-Wallace Krisztina, M., Michael E. Maguire. Regulation of CorA Mg2+ channel function affects the virulence of Salmonella enterica serovar typhimurium. Journal of bacteriology. 2008, 190.19, pp. 6509-6516.
35. Bearson Bradley, L., Lee, Wilson., John W. Foster. A low pH-inducible, PhoPQ-dependent acid tolerance response protects Salmonella typhimurium against inorganic acid stress. Journal of bacteriology. 1998, 180.9, pp. 2409–2417.
36. Hengge-Aronis, Regine. Signal transduction and regulatory mechanisms involved in control of the σS (RpoS) subunit of RNA polymerase. Microbiology and Molecular Biology Reviews. 2002, 66.3, pp. 373–395.
37. Moreno, Matthew. Regulation of sigma S degradation in Salmonella enterica var typhimurium: in vivo interactions between sigma S, the response regulator MviA (RssB) and ClpX. Journal of molecular microbiology and biotechnology. 2000, 2.2, pp. 245–254.
38. Cabeza María, L. Induction of RpoS degradation by the two-component system regulator RstA in Salmonella enterica. Journal of bacteriology. 2007, 189.20, pp. 7335–7342.
39. Tang, Tia. ClpXP affects the cell metabolism of Salmonella typhimurium partially in an RpoS-dependent manner. Metabolomics. 2017, 13.12, 157 p.
40. Lensmire Joshua M. Phosphate and carbohydrate facilitate the formation of filamentous Salmonella enterica during osmotic stress. Microbiology. 2018, 164.12, pp. 1503–1513.
41. Girard Mary, E. DksA and ppGpp regulate the σS stress response by activating promoters for the small RNA DsrA and the anti-adapter protein IraP. Journal of bacteriology. 2018, 200.2, e00463–17.
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