Emergence of Polymyxin B Resistance Influences Pathogenicity in Pseudomonas aeruginosa Mutators

ABSTRACT The interplay between polymyxin B pharmacodynamics and pathogenicity was examined in Pseudomonas aeruginosa PAO1 and isogenic DNA repair-deficient mutators (mutM and mutS strains). Against mutS mutators, polymyxin B initial killing was concentration dependent, with >99.9% bacterial reduction at 2 h followed by regrowth and resistance. The pre- versus postexposed strains were inoculated real time into Galleria mellonella waxworms, resulting in increased median survival times from 20 h to 23 h (P < 0.001). Emergence of resistance in mutS P. aeruginosa resulted in attenuation of virulence.

[1]  S. Gill,et al.  Evolution in Fast Forward: a Potential Role for Mutators in Accelerating Staphylococcus aureus Pathoadaptation , 2012, Journal of bacteriology.

[2]  A. Wong,et al.  Genomics of Adaptation during Experimental Evolution of the Opportunistic Pathogen Pseudomonas aeruginosa , 2012, PLoS genetics.

[3]  Boris M. Hartmann,et al.  Genetic Pathway in Acquisition and Loss of Vancomycin Resistance in a Methicillin Resistant Staphylococcus aureus (MRSA) Strain of Clonal Type USA300 , 2012, PLoS pathogens.

[4]  Shengchang Su,et al.  Epistatic Roles for Pseudomonas aeruginosa MutS and DinB (DNA Pol IV) in Coping with Reactive Oxygen Species-Induced DNA Damage , 2011, PloS one.

[5]  J. Weingarten,et al.  Pneumonia due to Pseudomonas aeruginosa: part I: epidemiology, clinical diagnosis, and source. , 2011, Chest.

[6]  M. Sutton,et al.  The GO system prevents ROS-induced mutagenesis and killing in Pseudomonas aeruginosa. , 2009, FEMS microbiology letters.

[7]  R. Hancock,et al.  Regulation of virulence and antibiotic resistance by two-component regulatory systems in Pseudomonas aeruginosa. , 2009, FEMS microbiology reviews.

[8]  G. Eliopoulos,et al.  Reduced susceptibility to vancomycin influences pathogenicity in Staphylococcus aureus infection. , 2009, The Journal of infectious diseases.

[9]  Patrick F. Smith,et al.  Attenuated Vancomycin Bactericidal Activity against Staphylococcus aureus hemB Mutants Expressing the Small-Colony-Variant Phenotype , 2008, Antimicrobial Agents and Chemotherapy.

[10]  A. Oliver,et al.  Hypermutation Is a Key Factor in Development of Multiple-Antimicrobial Resistance in Pseudomonas aeruginosa Strains Causing Chronic Lung Infections , 2005, Antimicrobial Agents and Chemotherapy.

[11]  Daniel G. Lee,et al.  The broad host range pathogen Pseudomonas aeruginosa strain PA14 carries two pathogenicity islands harboring plant and animal virulence genes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[12]  D. Livermore,et al.  Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  K. Tateda,et al.  Azithromycin Inhibits Quorum Sensing in Pseudomonas aeruginosa , 2001, Antimicrobial Agents and Chemotherapy.

[14]  D. Livermore,et al.  Antimicrobial susceptibility of Pseudomonas aeruginosa: results of a UK survey and evaluation of the British Society for Antimicrobial Chemotherapy disc susceptibility test. , 2001, The Journal of antimicrobial chemotherapy.

[15]  Ronald N. Jones,et al.  Contemporary Assessment of Antimicrobial Susceptibility Testing Methods for Polymyxin B and Colistin: Review of Available Interpretative Criteria and Quality Control Guidelines , 2001, Journal of Clinical Microbiology.

[16]  D. Stableforth,et al.  The Treatment of Respiratory Pseudomonas Infection in Cystic Fibrosis , 2000, Drugs.

[17]  A. Oliver,et al.  High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. , 2000, Science.

[18]  T. Beveridge,et al.  Virulence factors are released from Pseudomonas aeruginosa in association with membrane vesicles during normal growth and exposure to gentamicin: a novel mechanism of enzyme secretion , 1995, Journal of bacteriology.

[19]  E. Greenberg,et al.  Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[20]  S. Sonstein,et al.  Effect of low concentrations of quinolone antibiotics on bacterial virulence mechanisms. , 1993, Diagnostic microbiology and infectious disease.

[21]  N. Høiby,et al.  Frequent antibiotic therapy improves survival of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. , 1984, Acta paediatrica Scandinavica.

[22]  Mary Jane Ferraro,et al.  Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically : approved standard , 2000 .