Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa.
Keith P RomanoThulasi WarrierBradley E PoulsenPhuong H NguyenAlexander R LoftisAzin SaebiBradley L PenteluteDeborah T HungPublished in: Antimicrobial agents and chemotherapy (2019)
Pseudomonas aeruginosa is a major bacterial pathogen associated with a rising prevalence of antibiotic resistance. We evaluated the resistance mechanisms of P. aeruginosa against POL7080, a species-specific, first-in-class antibiotic in clinical trials that targets the lipopolysaccharide transport protein LptD. We isolated a series of POL7080-resistant strains with mutations in the two-component sensor gene pmrB Transcriptomic and confocal microscopy studies support a resistance mechanism shared with colistin, involving lipopolysaccharide modifications that mitigate antibiotic cell surface binding.
Keyphrases
- pseudomonas aeruginosa
- acinetobacter baumannii
- cystic fibrosis
- escherichia coli
- cell surface
- clinical trial
- biofilm formation
- toll like receptor
- drug resistant
- inflammatory response
- multidrug resistant
- klebsiella pneumoniae
- risk factors
- lps induced
- genome wide
- candida albicans
- gene expression
- immune response
- phase ii
- rna seq
- staphylococcus aureus
- genome wide identification
- phase iii