PhoQ Mutations Promote Lipid A Modification and Polymyxin Resistance of Pseudomonas aeruginosa Found in Colistin-Treated Cystic Fibrosis Patients

• DOI: 10.1128/aac.05391-11
• Publication Date: 2011-10-04T04:10:31Z
• Authors: Amanda K. Miller; Mark K. Brannon; Laurel Stevens; Helle Krogh Johansen; Sara E. Selgrade; Samuel I. Miller; Niels Høiby; Samuel M. Moskowitz
• Keywords: Polymyxin; Colistin; Polymyxin B; Lipid A

Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB PhoPQ regulatory systems confer low moderate levels of (MICs 8 64 mg/liter) laboratory clinical strains this organism. To explore role high-level resistance, P. with colistin MICs > 512 mg/liter had been isolated from cystic fibrosis patients treated inhaled (polymyxin E) were analyzed. Probable loss-of-function phoQ alleles found these conferred polymyxin. Partial complete suppressor phoP identified some resistance-conferring mutations, suggesting additional loci be involved aeruginosa. Disruption chromosomal presence an intact allele stimulated 4-amino-l-arabinose addition lipid A induced transcription promoter pmrH (arnB) operon, consistent known modification resistance. These results indicate contribute