Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria

By A. O. Olaitan, Serge Morand, J. Rolain. Frontiers in Microbiology, 2014

1,310 citations recorded by the source corpus.

Polymyxins are polycationic antimicrobial peptides that are currently the last-resort antibiotics for the treatment of multidrug-resistant, Gram-negative bacterial infections. The reintroduction of polymyxins for antimicrobial therapy has been followed by an increase in reports of resistance among Gram-negative bacteria. Some bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, develop resistance to polymyxins in a process referred to as acquired resistance, whereas other bacteria, such as Proteus spp., Serratia spp., and Burkholderia spp., are naturally resistant to these drugs. Reports of polymyxin resistance in clinical isolates have recently increased, including acquired and intrinsically resistant pathogens. This increase is considered a serious issue, prompting concern due to the low number of currently available effective antibiotics. This review summarizes current knowledge concerning the different strategies bacteria employ to resist the activities of polymyxins. Gram-negative bacteria employ several strategies to protect themselves from polymyxin antibiotics (polymyxin B and colistin), including a variety of lipopolysaccharide (LPS) modifications, such as modifications of lipid A with phosphoethanolamine and 4-amino-4-deoxy-L-arabinose, in addition to the use of efflux pumps, the formation of capsules and overexpression of the outer membrane protein OprH, which are all effectively regulated at the molecular level. The increased understanding of these mechanisms is extremely vital and timely to facilitate studies of antimicrobial peptides and find new potential drugs targeting clinically relevant Gram-negative bacteria.

Subfields: Epidemiology, Molecular Medicine, Pharmacology

View Paper: https://www.semanticscholar.org/paper/95083461dfac023640e4bb2709906282be271b00

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In Epidemiology

1. A. Croxatto
2. P. Nordmann

In Molecular Medicine

1. L. Poirel
2. P. Nordmann
3. Y. Doi
4. A. Jayol
5. A. Croxatto
6. K. Bush
7. J. Pitout
8. F. Codjoe

In Pharmacology

1. P. Nordmann
2. L. Poirel

Citations in the corpus

• Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes (2017, background): “Polymyxin resistance is regulated by the two-component systems PhoP/PhoQ and PmrA/PmrB (88), which respond to cation (calcium, iron, and magnesium) concentrations and pH variations.”
• Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019) (2020, background): “PhoQ and PmrA/PmrB systems [60], leading to the addition of either L-Ara4N or PEtN to LPS [13].”
• How to manage Pseudomonas aeruginosa infections (2018, methodology): “The alteration is characterized by a modification of the lipid A of the LPS by the addition of phosphoethanolamine (PEtN) and 4-amino-4-deoxy-Larabinose (L-Ara4N) [52].”
• Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections (2019, background): “Colistin resistance frequently results from the modification of the lipid A moiety of lipopolysaccharide (LPS) following the addition of 4-amino-4-deoxy-L-arabinose (47).”