Abstract
In recent years, the clinical and scientific interest in antibiotics known as polymyxin has increased greatly due to the large number of reports of multiresistant Gram-negative bacteria, among them Pseudomonas aeruginosa. This work aimed to investigate proteins responsible for resistance to polymyxins encoded in P. aeruginosa genomes using in silico tools. To do so, Escherichia coli MCR1 protein was used as bait. Sequences with similarities to MCR1 encoded in P. aeruginosa genomes were analyzed for physico-chemical properties including, theoretical molecular, isoelectric point, instability index, aliphatic index and hydropation index, secondary structures and protein domain. 31 Protein isoforms (EptA) more likely to confer resistance to polymyxin present in P. aeruginosa were determined. These proteins are between 465 and 521 amino acids in length. Molecular masses between 52.06 - 57.58 kDa, isoelectric point between 5.83 to 8.06, instability index between 60.33 to 66.42, aliphatic index between 99.980 to 107.39 and the hydropathy index between -0.038 to 0.037. These proteins belong to the DUF1705 superfamily with a Bit-score between 592,806 and 608,599. In conclusion the results evidenced the high degree of similarity between P. aeruginosa EpTAs including amino acids number, molecular mass, isoelectric point, instability index, aliphatic and hydrophobicity index, as well as secondary structures and protein domain with other proteins that confer resistance to polymyxins present in Gram-negative bacterial species of clinical interest. However, further studies are needed to identify the actual contribution of EptAs in P. aeruginosa species.
Highlights
In recent years, the clinical and scientific interest in antibiotics known as polymyxin has increased greatly due to the large number of reports of multiresistant Gram-negative bacteria, among them P. aeruginosa
In conclusion the results evidenced the high degree of similarity between EpTAs including amino acids number, molecular mass, isoelectric point, instability index, aliphatic and hydrophobicity index, as well as secondary structures and protein domain with other proteins that confer resistance to polymyxins present in Gram-negative bacterial species of clinical interest
In 2010, it was identified that H1-T6SS in P. aeruginosa has three effector proteins, namely Tse1-3, where Tse1 and Tse3 have the ability to cleave peptideoglycan associated with the bacterial envelope [4], and this function of H1-T6SS is directly linked to antibiotic resistance in biofilms [5]
Summary
Among the hypotheses about the mechanism of resistance acquired by the P. aeruginosa microorganism, the polymyxins are: (I) adaptive mechanism, being a direct consequence of the gradual adaptation to the presence of this antimicrobial associated with the culture medium used in clinical [1] or experimental diagnosis. Another possibility is interference during active transport through the membrane especially in the lipidic portion A of the endotoxin present in the lipopolysaccharide composition [2], resulting in loss of OMPs (Outer membrane proteins) or a reduction in interaction between polymyxin and envelope [3]; (II) genetic mutation mechanism, is associated to the increase of H1 (H1- T6SS) protein levels, cation substitution minimizing the Mg+2 concentration and increasing that of Ca+2 present in the membrane, reducing possible electrostatic interactions with polymyxin [4]. Resistance to polymyxins may be related to increased expression of the pmrC gene [6]
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