AiM  Vol.2 No.1 , March 2012
Differential Role of Two-Component Regulatory Systems (phoPQ and pmrAB) in Polymyxin B Susceptibility of Pseudomonas aeruginosa
ABSTRACT
Polymyxins are often considered as a last resort to treat multidrug resistant P. aeruginosa but polymyxin resistance has been increasingly reported worldwide in clinical isolates. Polymyxin resistance in P. aeruginosa is known to be associated with alterations in either PhoQ or PmrB. In this study, mutant strains of P. aeruginosa carrying amino acid substitution, a single and/or dual inactivation of PhoQ and PmrB were constructed to further understand the roles of PhoQ and PmrB in polymyxin susceptibility. Polymyxin B resistance was caused by both inactivation and/or amino acid substitutions in PhoQ but by only amino acid substitutions of PmrB. Alterations of both PhoQ and PmrB resulted in higher levels of polymyxin B resistance than alteration of either PhoQ or PmrB alone. These results were confirmed by time-killing assays suggesting that high-level polymyxin resistance in P. aeruginosa is caused by alterations of both PhoQ and PmrB.

Cite this paper
D. Owusu-Anim and D. Kwon, "Differential Role of Two-Component Regulatory Systems (phoPQ and pmrAB) in Polymyxin B Susceptibility of Pseudomonas aeruginosa," Advances in Microbiology, Vol. 2 No. 1, 2012, pp. 31-36. doi: 10.4236/aim.2012.21005.
References
[1]   N. Abraham and D. H. Kwon, “A Single Amino Acid Substitution in PmrB Is Associated with Polymyxin B Resistance in Clinical Isolate of Pseudomonas aeruginosa,” FEMS Microbiology Letters, Vol. 298, No. 2, 2009, pp. 249-254. doi:10.1111/j.1574-6968.2009.01720.x

[2]   J. A. Driscoll, S. L. Brody and M. H. Kollef, “The Epidemiology, Pathogenesis and Treatment of Pseudomonas aeruginosa Infections,” Drugs, Vol. 67, No. 3, 2007, pp. 351-368. doi:10.2165/00003495-200767030-00003

[3]   T. P. Lodise, C. D. Miller, J. Graves, J. P. Furuno, J. C. McGregor, B. Lomaestro, et al., “Clinical Prediction Tool to Identify Patients with Pseudomonas aeruginosa Respiratory Tract Infections at Greatest Risk for Multidrug Resistance,” Antimicrobial Agents and Chemotherapy, Vol. 51, No. 2, 2007, pp. 417-422. doi:10.1128/AAC.00851-06

[4]   C. S. McVay, M. Velasquez and J. A. Fralick, “Phage Therapy of Pseudomonas aeruginosa Infection in a Mouse Burn Wound Model,” Antimicrobial Agents and Chemotherapy, Vol. 51, No. 6, 2007, pp. 1934-1938. doi:10.1128/AAC.01028-06

[5]   R. Mittal, R. K. Khandwaha, V. Gupta, P. K. Mittal and K. Harjai, “Phenotypic Characters of Urinary Isolates of Pseudomonas aeruginosa & Their Association with Mouse Renal Colonization,” The Indian Journal of Medical Research, Vol. 123, No. 1, 2006, pp. 67-72.

[6]   J. Li, R. L. Nation, J. D. Turnidge, R. W. Milne, K. Coulthard and C. R. Rayner, et al., “Colistin: The Re-Emerging Antibiotic for Multidrug-Resistant Gram-Negative Bacterial Infections,” The Lancet Infectious Diseases, Vol. 6, No. 9, 2006, pp. 589-601. doi:10.1016/S1473-3099(06)70580-1

[7]   T. M. Arnold, G. N. Forres and K. J. Messmer, “Polymyxin Antibiotics for Gram-Negative Infections,” American Journal of Health-System Pharmacy, Vol. 64, No. 8, 2007, pp. 819-826. doi:10.2146/ajhp060473

[8]   M. E. Falagas, P. I. Rafailidis, D. K. Matthaiou, S. Virtzili, D. Nikita and A. Michalopoulos, “Pandrug-Resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii Infections: Characteristics and Outcome in a Series of 28 Patients,” International Journal of Antimicrobial Agents, Vol. 32, No. 5, 2008, pp. 450-454. doi:10.1016/j.ijantimicag.2008.05.016

[9]   C. Y. Wang, J. S. Jerng, K. Y. Chen, L. N. Lee, C. J. Yu, P. R. Hsueh, et al., “Pandrug-Resistant Pseudomonas aeruginosa among Hospitalised Patients: Clinical Features, Risk-Factors and Outcomes,” Clinical Microbiology and Infection, Vol. 12, No. 1, 2006, pp. 63-68. doi:10.1111/j.1469-0691.2005.01305.x

[10]   M. E. Falagas and I. A. Bliziotis, “Pandrug-Resistant Gram-Negative Bacteria: The Dawn of the Post-Antibiotic Era?” International Journal of Antimicrobial Agents, Vol. 29, No. 6, 2007, pp. 630-636. doi:10.1016/j.ijantimicag.2006.12.012

[11]   D. Landman, S. Bratu, M. Alam and J. Quale, “Citywide Emergence of Pseudomonas aeruginosa Strains with Reduced Susceptibility to Polymyxin B,” Journal of Antimicrobial Chemotherapy, Vol. 55, No. 6, 2005, pp. 954- 957. doi:10.1093/jac/dki153

[12]   S. Gupta, D. Govil, P. N. Kakar, O. Prakash, D. Arora, S. Das, et al., “Colistin and Polymyxin B: A Re-Emergence,” Indian Journal of Critical Care Medicine, Vol. 13, No. 2, 2009, pp. 49-53. doi:10.4103/0972-5229.56048

[13]   A. P. Zavascki, L. Z. Goldani, J. Li and R. L. Nation, “Polymyxin B for the Treatment of Multidrug-Resistant Pathogens: A Critical Review,” Journal of Antimicrobial Chemotherapy, Vol. 60, No. 6, 2007, pp. 1206-1215. doi:10.1093/jac/dkm357

[14]   M. R. Yeaman and N. Y. Yount, “Mechanisms of Antimicrobial Peptide Action and Resistance,” Pharmacological Reviews, Vol. 55, No. 1, 2003, pp. 27-55. doi:10.1124/pr.55.1.2

[15]   E. L. Macfarlane, A. Kwasnicka and R. E. Hancock, “Role of Pseudomonas aeruginosa PhoP-PhoQ in Resis- tance to Antimicrobial Cationic Peptides and Aminoglycosides,” Microbiology, Vol. 146, No. 10, 2000, pp. 2543- 2554.

[16]   E. L. Macfarlane, A. Kwasnicka, M. M. Ochs and R. E. Hancock, “PhoP-PhoQ Homologues in Pseudomonas aeruginosa Regulate Expression of the Outer-Membrane Protein OprH and Polymyxin B Resistance,” Molecular Microbiology, Vol. 34, No. 2, 1999, pp. 305-316. doi:10.1046/j.1365-2958.1999.01600.x

[17]   J. B. McPhee, M. Bains, G. Winsor, S. Lewenza, A. Kwasnicka, M. D. Brazas, et al., “Contribution of the PhoP-PhoQ and PmrA-PmrB Two-Component Regulatory Systems to Mg2+-Induced Gene Regulation in Pseudomonas aeruginosa,” Journal of Bacteriology, Vol. 188, No. 11, 2006, pp. 3995-4006. doi:10.1128/JB.00053-06

[18]   J. B. McPhee, S. Lewenza and R. E. Hancock, “Cationic Antimicrobial Peptides Activate a Two-Component Regulatory System, PmrA-PmrB, That Regulates Resistance to Polymyxin B and Cationic Antimicrobial Peptides in Pseudomonas aeruginosa,” Molecular Microbiology, Vol. 50, No. 1, 2003, pp. 205-217. doi:10.1046/j.1365-2958.2003.03673.x

[19]   K. Barrow and D. H. Kwon, “Alterations in Two-Component Regulatory Systems of phoPQ and pmrAB Are Associated with Polymyxin B Resistance in Clinical Isolates of Pseudomonas aeruginosa,” Antimicrobial Agents and Chemotherapy, Vol. 53, No. 12, 2009, pp. 5150-5154. doi:10.1128/AAC.00893-09

[20]   S. M. Moskowitz, R. K. Ernst and S. I. Miller, “pmrAB, a Two-Component Regulatory System of Pseudomonas aeruginosa That Modulates Resistance to Cationic Antimicrobial Peptides and Addition of Aminoarabinose to Lipid A,” Journal of Bacteriology, Vol. 186, No. 2, 2004, pp. 575-579.

[21]   S. M. Park, C. D. Lu and A. T. Abdelal, “Cloning and Characterization of argR, a Gene That Participates in Regulation of Arginine Biosynthesis and Catabolism in Pseudomonas aeruginosa PAO1,” Journal of Bacteriology, Vol. 179, No. 17, 1997, pp. 5300-5308.

[22]   S. Stibitz, W. Black and S. Falkow, “The Construction of a Cloning Vector Designed for Gene Replacement in Bordetella pertussis,” Gene, Vol. 50, No. 1-3, 1986, pp. 133- 140. doi:10.1016/0378-1119(86)90318-5

[23]   M. J. Gambello and B. H. Iglewski, “Cloning and Characterization of the Pseudomonas aeruginosa lasR Gene, a Transcriptional Activator of Elastase Expression,” Journal of Bacteriology, Vol. 173, No. 9, 1991, pp. 3000-3009.

[24]   C. A. Trieber and D. E. Taylor, “Mutations in the 16S rRNA Genes of Helicobacter pylori Mediate Resistance to Tetracycline,” Journal of Bacteriology, Vol. 184, No. 8, 2002, pp. 2131-2140. doi:10.1128/JB.184.8.2131-2140.2002

[25]   D. H. Kwon and C. D. Lu, “Polyamines Induce Resis- tance to Cationic Peptide, Aminoglycoside, and Quinolone Antibiotics in Pseudomonas aeruginosa PAO1,” Antimicrobial Agents and Chemotherapy, Vol. 50, No. 5, 2006, pp. 1615-1622. doi:10.1128/AAC.50.5.1615-1622.2006

 
 
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