OJAS  Vol.5 No.4 , October 2015
Molecular Significance of lon and cpxR Genes in the Pathogenicity of Salmonella
Abstract: The important foodborne zoonotic pathogen Salmonella causes gastroenteritis. The dynamics of host-pathogen Salmonella interaction and infection might enhance the development of novel tar-geted preventative measures and drug regimens. The lon and cpxR are virulence associated genes, which have an important role in the Salmonella pathogenesis. However, the deletions of lon and cpxRlead to the construction of genetically engineered live Salmonella vaccine candidate. In this review, lon and cpxR genes are focused for their involvement in Salmonella pathogenesis. Furthermore, the importance of these genes was briefly emphasized during the construction of Salmonella vaccine candidate.
Cite this paper: Nandre, R. and Mahajan, P. (2015) Molecular Significance of lon and cpxR Genes in the Pathogenicity of Salmonella. Open Journal of Animal Sciences, 5, 429-434. doi: 10.4236/ojas.2015.54045.

[1]   Dhanoa, A. and Fatt, Q.K. (2009) Non-Typhoidal Salmonella Bacteraemia: Epidemiology, Clinical Characteristics and Its’ Association with Severe Immunosuppression. Annals of Clinical Microbiology and Antimicrobials, 8, 15.

[2]   Matheson, N., Kingsley, R.A., Sturgess, K., Aliyu, S.H., Wain, J., et al. (2010) Ten Years Experience of Salmonella Infections in Cambridge, UK. Journal of Infection, 60, 21-25.

[3]   Scallan, E., Hoekstra, R.M., Angulo, F.J., Tauxe, R.V., Widdowson, M.A., et al. (2011) Foodborne Illness Acquired in the United States—Major Pathogens. Emerging Infectious Diseases, 17, 7-15.

[4]   Hale, C.R., Scallan, E., Cronquist, A.B., Dunn, J., Smith, K., et al. (2012) Estimates of Enteric Illness Attributable to Contact with Animals and Their Environments in the United States. Clinical Infectious Diseases, 54, S472-S479.

[5]   Takaya, A., Tomoyasu, T., Tokumitsu, A., Morioka, M. and Yamamoto, T. (2002) The ATP Dependent Lon Protease of Salmonella enterica Serovar Typhimurium Regulates Invasion and Expression of Genes Carried on Salmonella Pathogenicity Island 1. Journal of Bacteriology, 184, 224-232.

[6]   Darwin, K.H. and Miller, V.L. (1999) Molecular Basis of the Interaction of Salmonella with the Intestinal Mucosa. Clinical Microbiology Reviews, 12, 405-428.

[7]   Hansen-Wester, I. and Hensel, M. (2001) Salmonella Pathogenicity Island Encoding Type III Secretion Systems. Microbes and Infection, 3, 549-559.

[8]   Beal, R.K., Powers, C., Davison, T.F., Barrow, P.A. and Smith, A.L. (2006) Clearance of Enteric Salmonella enterica Serovar Typhimurium in Chickens is Independent of B-Cell Function. Infection and Immunity, 74, 1442-1444.

[9]   Curtiss, R., Kelly, S.M. and Hassan, J.O. (1993) Live Oral Avirulent Salmonella Vaccines. Veterinary Microbiology, 37, 397-405.

[10]   Okamura, M., Tachizaki, H., Kubo, T., Kikuchi, S., Suzuki, A., et al. (2007) Comparative Evaluation of a Bivalent Killed Salmonella vaccine to Prevent Egg Contamination with Salmonella enterica Serovars Enteritidis, Typhimurium, and Gallinarum Biovar Pullorum, Using 4 Different Challenge Models. Vaccine, 25, 4837-4844.

[11]   Takaya, A., Suzuki, M., Matsui, H., Tomoyasu, T., Sashinami, H., et al. (2003) Lon, a Stress-Induced ATP-Dependent Protease, Is Critically Important for Systemic Salmonella enterica Serovar Typhimurium Infection of Mice. Infection and Immunity, 71, 690-696.

[12]   Matsui, H., Suzuki, M., Isshiki, Y., Kodama, C., Eguchi, M., et al. (2003) Oral Immunization with ATP-Dependent Protease-Deficient Mutants Protects Mice against Subsequent Oral Challenge with Virulent Salmonella enterica Serovar Typhimurium. Infection and Immunity, 71, 30-39.

[13]   Kim, S.W., Moon, K.H., Baik, H.S., Kang, H.Y., Kim, S.K., et al. (2009) Changes of Physiological and Biochemical Properties of Salmonella enterica Serovar Typhimurium by Deletion of cpxR and lon Genes Using Allelic Exchange Method. Journal of Microbiological Methods, 79, 314-320.

[14]   Matsuda, K., Chaudhari, A.A., Kim, S.W., Lee, K.M. and Lee, J.H. (2010) Physiology, Pathogenicity and Immunogenicity of Lon and/or cpxR Deleted Mutants of Salmonella gallinarum as Vaccine Candidates for Fowl Typhoid. Veterinary Research, 41, 59.

[15]   Nandre, R.M., Matsuda, K., Chaudhari, A.A., Kim, B. and Lee, J.H. (2012) A Genetically Engineered Derivative of Salmonella enteritidis as a Novel Live Vaccine Candidate for Salmonellosis in Chickens. Research in Veterinary Science, 93, 596-603.

[16]   Rep, M., van Dij, J.M., Suda, K., Schatz, G., Grivell, L.A., et al. (1996) Promotion of Mitochondrial Membrane Complex Assembly by a Proteolytically Inactive Yeast Lon. Science, 274, 103-106.

[17]   Chung, C.H. (1993) Proteases of Escherichia coli. Science, 262, 372-374.

[18]   Gottesman, S. (1996) Proteases and Their Targets in Escherichia coli. Annual Review of Genetics, 30, 465-506.

[19]   Smith, C.K., Baker, T.A. and Sauger, R.T. (1999) Lon and Clp Family Protease and Chaperones Share Homologous Substrate-Recognition Domains. Proceedings of the National Academy of Sciences of the United States of America, 96, 6678-6682.

[20]   Amerik, A.Y., Antonov, V.K., Gorbalenya, A.E., Kotova, S.A., Rotanova, T.V., et al. (1991) Site-Directed Mutagenesis of La Protease. A Catalytically Active Serine Residue. FEBS Letters, 287, 211-214.

[21]   Goldberg, A.L. (1992) The Mechanism and Functions of ATP-Dependent Proteases in Bacterial and Animal Cells. European Journal of Biochemistry, 203, 9-23.

[22]   Takaya, A., Kubota, Y., Isogai, E. and Yamamoto, T. (2005) Degradation of the HilC and HilD Regulator Proteins by ATP-Dependent Lon Protease Leads to Downregulation of Salmonella Pathogenicity Island 1 Gene Expression. Molecular Microbiology, 55, 839-852.

[23]   Kultz, D. (2005) Molecular and Evolutionary Basis of the Cellular Stress Response. Annual Review of Physiology, 67, 225-257.

[24]   Majdalani, N. and Gottesman, S. (2005) The Rcs Phosphorelay: A Complex Signal Transduction System. Annual Review of Microbiology, 59, 379-405.

[25]   Ngo, J.K. and Davies, K.J. (2009) Mitochondrial Lon Protease Is a Human Stress Protein. Free Radical Biology and Medicine, 46, 1042-1048.

[26]   Langklotz, S. and Narberhaus, F. (2011) The Escherichia coli Replication Inhibitor CspD Is Subject to Growth-Regulated Degradation by the Lon Protease. Molecular Microbiology, 80, 1313-1325.

[27]   Flanagan, J.M. and Bewley, M.C. (2002) Protein Quality Control in Bacterial Cells: Integrated Networks of Chaperones and ATP-Dependent Proteases. Genetic Engineering, 24, 17-47.

[28]   Torres-Cabassa, A.S. and Gottesman, S. (1987) Capsule Synthesis in Escherichia coli K-12 Is Regulated by Proteolysis. Journal of Bacteriology, 169, 981-989.

[29]   Schmidt, R., Decatur, A., Rather, P., Moran Jr., C. and Losick, R. (1994) Bacillus subtilis lon Protease Prevents Inappropriate Transcription of Genes under the Control of the Sporulation Transcription Factor Sigma G. Journal of Bacteriology, 176, 6528-6537.

[30]   Wright, R., Stephens, C., Zweiger, G., Shapiro, L., Alley, A., et al. (1996) Caulobacter Lon Protease Has a Critical Role in Cell-Cycle Control of DNA Methylation. Genes & Development, 10, 1532-1542.

[31]   Stewart, B., Enos-Berlage, J. and McCarter, L. (1997) The lonS Gene Regulates Swarmer Cell Differentiation of Vibrio parahaemolyticus. Journal of Bacteriology, 179, 107-114.

[32]   Bretz, J., Losada, L., Lisboa, K. and Hutcheson, S. (2002) Lon Protease Functions as a Negative Regulator of Type III Protein Secretion in Pseudomonas syringae. Molecular Microbiology, 45, 397-409.

[33]   Kuroda, A., Nomura, K., Ohtomo, R., Kato, J., Ikeda, T., et al. (2001) Role of Inorganic Polyphosphate in Promoting Ribosomal Protein Degradation by the Lon Protease in E. coli. Science, 293, 705-708.

[34]   Christensen, S., Maenhaut-Michel, G., Mine, N., Gottesman, S., Gerdes, K., et al. (2004) Overproduction of the Lon Protease Triggers Inhibition of Translation in Escherichia coli: Involvement of the yefM-yoeB Toxin-Antitoxin System. Molecular Microbiology, 51, 1705-1717.

[35]   Silhavy, T.J., Kahne, D. and Walker, S. (2010) The Bacterial Cell Envelope. Cold Spring Harbor Perspectives in Biology, 2, Article ID: a000414.

[36]   Erickson, J.W. and Gross, C.A. (1989) Identification of the Sigma E Subunit of Escherichia coli RNA Polymerase: A Second Alternate Sigma Factor Involved in High-Temperature Gene Expression. Genes & Development, 3, 1462-1471.

[37]   Lipinska, B., Sharma, S. and Georgopoulos, C. (1988) Sequence Analysis and Regulation of the htrA Gene of Escherichia coli: A Sigma 32-Independent Mechanism of Heat-Inducible Transcription. Nucleic Acids Research, 16, 10053-10067.

[38]   Pogliano, J., Lynch, A.S., Belin, D., Lin, E.C. and Beckwith, J. (1997) Regulation of Escherichia coli Cell Envelope Proteins Involved in Protein Folding and Degradation by the Cpx Two-Component System. Genes & Development, 11, 1169-1182.

[39]   Raivio, T.L. and Silhavy, T.J. (1997) Transduction of Envelope Stress in Escherichia coli by the Cpx Two-Component System. Journal of Bacteriology, 179, 7724-7733.

[40]   Raffa, R.G. and Raivio, T.L. (2002) A Third Envelope Stress Signal Transduction Pathway in Escherichia coli. Molecular Microbiology, 45, 1599-1611.

[41]   MacRitchie, D.M., Buelow, D.R., Price, N.L. and Raivio, T.L. (2008) Two-Component Signaling and Gram Negative Envelope Stress Response Systems. Advances in Experimental Medicine and Biology, 631, 80-110.

[42]   Stock, A.M., Robinson, V.L. and Goudreau, P.N. (2000) Two Component Signal Transduction. Annual Review of Biochemistry, 69, 183-215.

[43]   Dorel, C., Lejeune, P. and Rodrigue, A. (2006) The Cpx System of Escherichia coli, a Strategic Signaling Pathway for Confronting Adverse Conditions and for Settling Biofilm Communities? Research in Microbiology, 157, 306-314.

[44]   Hung, D.L., Raivio, T.L., Jones, C.H., Silhavy, T.J. and Hultgren, S.J. (2001) Cpx Signaling Pathway Monitors Biogenesis and Affects Assembly and Expression of P pili. The EMBO Journal, 20, 1508-1518.

[45]   Wolfe, A.J., Parikh, N., Lima, B.P. and Zemaitaitis, B. (2008) Signal Integration by the Two Competent Signal Transduction Response Regulator CpxR. Journal of Bacteriology, 190, 2314-2322.

[46]   Takaya, A., Suzuki, A., Kikuchi, Y., Eguchi, M., et al. (2005) Derepression of Salmonella Pathogenicity Island 1 Genes within Macrophages Leads to Rapid Apoptosis via Caspase-1- and Caspase-3-Dependent Pathways. Cellular Microbiology, 7, 79-90.

[47]   Nakayama, S., Kushiro, A., Asahara, T., Tanaka, R., Hu, L., et al. (2003) Activation of hilA Expression at Low pH Requires the Signal Sensor CpxA, but Not the Cognate Response Regulator CpxR, in Salmonella enterica Serovar Typhimurium. Microbiology, 149, 2809-2817.

[48]   Hur, J. and Lee, J.H. (2010) Immunization of Pregnant Sows with a Novel Virulence Gene Deleted Live Salmonella Vaccine and Protection of Their Suckling Piglets against Salmonellosis. Veterinary Microbiology, 143, 270-276.

[49]   Jeon, B.W., Jawale, C.V., Kim, S.H. and Lee, J.H. (2012) Attenuated Salmonella Gallinarum Secreting an Escherichia coli Heat-Labile Enterotoxin B Subunit Protein as an Adjuvant for Oral Vaccination against Fowl Typhoid. Veterinary Immunology and Immunopathology, 150, 149-160.

[50]   Nandre, R.M., Jawale, C.V. and Lee, J.H. (2013) Enhanced Protective Immune Responses against Salmonella Enteritidis Infection by Salmonella Secreting an Escherichia coli Heat-Labile Enterotoxin B Subunit Protein. Comparative Immunology, Microbiology and Infectious Diseases, 36, 536-548.

[51]   Nandre, R.M., Jawale, C.V. and Lee, J.H. (2013) Adjuvant Effect of Escherichia coli Heat Labile Enterotoxin B Subunit against Internal Egg Contamination in Domestic Fowl Immunized with a Live Salmonella enteric Serovar Enteritidis Vaccine. The Veterinary Journal, 197, 861-867.

[52]   Nandre, R., Matsuda, K. and Lee, J.H. (2014) Efficacy for a New Live Attenuated Salmonella enteritidis Vaccine Candidate to Reduce Internal Egg Contamination. Zoonoses and Public Health, 61, 55-63.