Colistin Resistance in Aeromonas spp

Abstract

The increase in the use of antimicrobials such as colistin for the treatment of infectious diseases has led to the appearance of Aeromonas strains resistant to this drug. However, resistance to colistin not only occurs in the clinical area but has also been determined in Aeromonas isolates from the environment or animals, which has been determined by the detection of mcr genes that confer a resistance mechanism to colistin. The variants mcr-1, mcr-3, and mcr-5 have been detected in the genus Aeromonas in animal, environmental, and human fluids samples. In this article, an overview of the resistance to colistin in Aeromonas is shown, as well as the generalities of this molecule and the recommended methods to determine colistin resistance to be used in some of the genus Aeromonas.

Keywords: Aeromonas; antimicrobial resistance; colistin.

Figure 1

Polymyxin or colistin structure. Basic structure of polymyxin E composed of a chain of 6-methyl-octanoic acid (fatty acid), linked to a cyclic lipopeptide of 10 amino acids. 1, diaminobutyric acid (L-Dab); 2, threonine (L-Thr); 3, diaminobutyric acid (L-Dab); 4–5, diaminobutyric acid (L-Dab); 6, leucine (D-Leu); 7, leucine (L-Leu); 8–9, diaminobutyric acid (L-Dab); 10, threonine (L-Thr). The residues in position 6 of D-Leu and L-Leu in position 7 determine polymyxin E. Amino acid substitution at positions 6 and 7 determines the colistin subtype. The loop is formed by the amino acids from position 4 to 10. This cyclic peptide is composed of non-proteinogenic amino acids (D-Leu; L-Dab) and contains an isopeptide bond linking amino acids 4 and 10. These characteristics make the peptide resistant to the action of most peptidases/proteases and indicate that the compound originates from a non-ribosomal protein synthesis (NRPS) biosynthetic pathway. Modified from PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/Colistin#section=Names-and-Identifiers, access date: 21 May 2021).

Figure 2

Colistin mechanism of action. (A) The positively charged colistin molecule interacts with the negative charges of the LPS membrane, resulting in the release of Ca²⁺/Mg²⁺ ions. (B) This interaction results in a membrane disruption, therefore, the output of Ca²⁺/Mg²⁺ ions is generated. Finally, colistin enters the cytoplasm and inhibits the activity of the oxidoreductases enzyme (NDH₂). Generated from this work.

Figure 3

Bacterial mechanisms of resistance to colistin. The different mechanisms of resistance to colistin described in Gram-negative bacilli and other bacteria are presented: the mechanism mediated by the mcr genes, those regulated by the phoP and phoQ proteins, others regulated by the pmr proteins or by the iptxT and etk genes, and operons that encode activation proteins of pmr proteins [11,30,31,32]. Generated from this work.