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Colistin Resistance in Aeromonas Spp

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Colistin Resistance in Aeromonas Spp International Journal of Molecular Sciences Review Colistin Resistance in Aeromonas spp. Luis Uriel Gonzalez-Avila 1, Miguel Angel Loyola-Cruz 1,2, Cecilia Hernández-Cortez 3 , Juan Manuel Bello-López 2 and Graciela Castro-Escarpulli 1,* 1 Laboratorio de Investigación Clínica y Ambiental, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala, Col. Casco de Santo Tomás, Ciudad de México 11340, Mexico; [email protected] (L.U.G.-A.); [email protected] (M.A.L.-C.) 2 División de Investigación, Hospital Juárez de México, Av Instituto Politécnico Nacional 5160, Magdalena de las Salinas, Gustavo A. Madero, Ciudad de México 07760, Mexico; [email protected] 3 Laboratorio de Bioquímica Microbiana, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala, Col. Casco de Santo Tomás, Ciudad de México 11340, Mexico; [email protected] * Correspondence: [email protected]; Tel.: +51-1-55-5729-6000 (ext. 62571) 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. Citation: Gonzalez-Avila, L.U.; Loyola-Cruz, M.A.; Keywords: colistin; antimicrobial resistance; Aeromonas Hernández-Cortez, C.; Bello-López, J.M.; Castro-Escarpulli, G. Colistin Resistance in Aeromonas spp. Int. J. Mol. Sci. 2021, 22, 5974. https:// 1. Introduction doi.org/10.3390/ijms22115974 Colistin is a lipopeptide antibiotic from the group of polymyxins. It has a cyclic peptide chain that is linked to a fatty acid. Colistin is used in the medical field, since it is Academic Editors: Baltasar Mayo and an extended-spectrum antimicrobial, and it is used as a last line of treatment in human Ana Belén Flórez infections that are caused by Gram-negative bacilli [1]. Until 2016, resistance to colistin was reported in some genera of bacteria intrinsically and contained in the bacterial genophore, Received: 26 April 2021 until the presence of a gene called mcr, present in a plasmid that confers resistance to this Accepted: 26 May 2021 Published: 1 June 2021 antimicrobial, was detected in an Escherichia coli strain [2]. After this report, the number of isolates of various origins with mcr genes and a colistin resistance phenotype was Publisher’s Note: MDPI stays neutral increased; in addition, it was found that resistance to this molecule could be transferred with regard to jurisdictional claims in horizontally [3,4]. published maps and institutional affil- The use of colistin as a treatment for infections increased after the appearance of iations. multidrug resistance phenotypes (MDR) in Gram-negative bacilli and the appearance of carbapenemase-producing enterobacteria type KPC (Klebsiella pneumoniae carbapenemase) or NDM (New Delhi metallo-β-lactamase), in addition to Gram-negative bacilli classified as XDR (extensively drug resistant) that continue to appear, especially in bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and other Gram-negative bacilli, such Copyright: © 2021 by the authors. Aeromonas Licensee MDPI, Basel, Switzerland. as , which is also of medical and veterinary importance and is isolated from This article is an open access article environmental samples [5,6]. distributed under the terms and Aeromonas is a Gram-negative bacillus, positive for oxidase and catalase tests, a glucose conditions of the Creative Commons fermenter, and it is resistant to vibriostatic O/129 (2,4-diamino-6,7-diisopropylpteridine) [7]. Attribution (CC BY) license (https:// In humans, it can cause intestinal and extra-intestinal infections. It is important in the creativecommons.org/licenses/by/ medical area, mainly in patients with diarrhea, or with infections in the skin and soft tissue; 4.0/). moreover, it can cause bacteremia, which progresses to sepsis, or endocarditis [8,9]. Int. J. Mol. Sci. 2021, 22, 5974. https://doi.org/10.3390/ijms22115974 https://www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2021, 22, x FOR PEER REVIEW 2 of 10 [7]. In humans, it can cause intestinal and extra-intestinal infections. It is important in the med- Int. J. Mol. Sci. 2021, 22, 5974 2 of 10 ical area, mainly in patients with diarrhea, or with infections in the skin and soft tissue; more- over, it can cause bacteremia, which progresses to sepsis, or endocarditis [8,9]. The genus Aeromonas is widely distributed in diverse ecosystems; however, it is a bacteriumThe genus nativeAeromonas to aquatic issystems, widely hence distributed the largest in diverse number ecosystems; of isolates are however, from water. it is a Isolatesbacterium have native been to obtained aquatic systems,from drinking hence thewater, largest wastewater, number ofbottled isolates water, are from seawater, water. andIsolates deep have and beensurface obtained water fromsamples. drinking Food water, isolates wastewater, have been bottled obtained water, from seawater, vegetables, and fruits,deep andpork, surface poultry, water and samples. beef, as Foodwell isolatesas seafood have and been fish. obtained In animals, from it vegetables, is considered fruits, a pathogen,pork, poultry, especially and beef, in fish, as well in which as seafood it can and cause fish. furunculosis, In animals, it ulcers, is considered and hemorrhages, a pathogen, amongespecially other in diseases. fish, in which This pathogen it can cause has furunculosis, also been isolated ulcers, from and hemorrhages,infections in rabbits, among dogs,other cats, diseases. chickens, This pathogenhorses, and has crustaceans also been isolated[8,9]. from infections in rabbits, dogs, cats, chickens, horses, and crustaceans [8,9]. 2. The Colistin Situation 2. The Colistin Situation Colistin is a lipopeptide molecule that is included in the polymyxin family. This mol- Colistin is a lipopeptide molecule that is included in the polymyxin family. This ecule has a peptide chain that is made up of 10 amino acids and is linked to a fatty acid. It molecule has a peptide chain that is made up of 10 amino acids and is linked to a fatty acid. has surface-active properties that alter the permeability of the Gram-negative membrane It has surface-active properties that alter the permeability of the Gram-negative membrane in contact with lipopolysaccharides (LPS), resulting in cell death due to the electrostatic in contact with lipopolysaccharides (LPS), resulting in cell death due to the electrostatic attraction that is exerted between the positive charge of the amino groups and the anions, attraction that is exerted between the positive charge of the amino groups and the anions, phosphate, and carboxylate (Figure 1) [1,3,4]. phosphate, and carboxylate (Figure1)[1,3,4]. Figure 1. Polymyxin or colistin structure. Basic structure of polymyxin E composed of a chain of 6-methyl-octanoic acid (fatty Figure 1. Polymyxin or colistin structure. Basic structure of polymyxin E composed of a chain of 6-methyl-octanoic acid acid), linked to a cyclic lipopeptide of 10 amino acids. 1, diaminobutyric acid (L-Dab); 2, threonine (L-Thr); 3, diaminobutyric (fatty acid), linked to a cyclic lipopeptide of 10 amino acids. 1, diaminobutyric acid (L-Dab); 2, threonine (L-Thr); 3, dia- minobutyricacid (L-Dab); acid 4–5, (L-Dab); diaminobutyric 4–5, diaminobutyric acid (L-Dab); acid 6, leucine (L-Dab); (D-Leu); 6, leucine 7, leucine (D-Leu); (L-Leu); 7, leucine 8–9, diaminobutyric(L-Leu); 8–9, diaminobutyric acid (L-Dab); acid10, threonine (L-Dab); 10, (L-Thr). threonine The residues(L-Thr). The in position residues 6 in of positi D-Leuon and 6 of L-Leu D-Leu in and position L-Leu 7 in determine position 7 polymyxin determine E.polymyxin Amino acid E. Aminosubstitution acid substitution at positions 6at andpositions 7 determines 6 and 7 thedetermines colistin subtype. the colistin The subtype. loop is formedThe loop by is the formed amino by acids the amino from position acids from 4 to position10. This 4 cyclic to 10. peptide This cyclic is composed peptide is of composed non-proteinogenic of non-proteinogenic amino acids amino (D-Leu; acids L-Dab) (D-Leu and; containsL-Dab) and an isopeptidecontains an bond iso- peptidelinking aminobond linking acids 4 amino and 10. acids These 4 and characteristics 10. These characteristics make the peptide make resistant the peptide to the resistant action of to most the peptidases/proteasesaction of most pepti- dases/proteasesand indicate that and the indicate compound that originates the compound from a originates non-ribosomal from proteina non-ribosomal synthesis (NRPS)protein biosyntheticsynthesis (NRPS) pathway. biosynthetic Modified pathway.from PubChem Modified (https://pubchem.ncbi.nlm.nih.gov/compound/Colistin#section=Names-and-Identifiers from PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/Colistin#section=Names-and-Identifi-, access date: 21 ers, access date: 21 May 2021). May 2021). ThisThis molecule molecule contains contains a a structure structure called called a a cyclic cyclic loop, loop, formed formed by by the the seven amino acidsacids that that are are among among the the amino amino group group of of the the di diaminobutyricaminobutyric acid acid side side chain chain in inposition position 4 and4 and the the carboxyl carboxyl group group of of the the terminal terminal carbon carbon of of residue residue number number 10 10 of of threonine threonine (Thr).
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