Abstract
Polymyxins are one of most important antibiotics available for multidrug-resistant Gram-negative infections. Diverse chromosomal resistance mechanisms have been described, but the polymyxin resistance phenotype is not yet completely understood. The objective of this study was to characterize colistin resistant mcr-1-producing strains isolated from human infections over one year in a hospital setting (Hospital das Clínicas, São Paulo, Brazil). We isolated 490 colistin-resistant Gram-negative rods, of which eight were mcr-1.1-positive Escherichia coli, the only species with this result, indicating a low incidence of the mcr-1 production mechanism among colistin-resistant isolates. All mcr-1.1 positive isolates showed similarly low MICs for colistin and were susceptible to most antibiotics tested. The isolates showed diversity of MLST classification. The eight mcr-1.1-positive E. coli genomes were sequenced. In seven of eight isolates the mcr-1.1 gene is located in a contig that is presumed to be a part of an IncX4 plasmid; in one isolate, it is located in a contig that is presumed to be part of an IncHI2A plasmid. Three different genomic contexts for mcr-1.1 were observed, including a genomic cassette mcr-1.1-pap2 disrupting a DUF2806 domain-containing gene in six isolates. In addition, an IS1-family transposase was found inserted next to the mcr-1.1 cassette in one isolate. An mcr-1.1-pap2 genomic cassette not disrupting any gene was identified in another isolate. Our results suggest that plasmid dissemination of hospital-resident strains took place during the study period and highlight the need for continued genomic surveillance.
Highlights
Multidrug-resistant Gram-negative bacterial clinical isolates are responsible for high mortality rates worldwide (Agência Nacional de Vigilância Sanitária, 2016; De Waele et al, 2020), and constitute a challenge for healthcare professionals with respect to therapy choice, because few options are currently available
During one year of investigation, 7,852 Gram-negative bacilli were isolated in the hospital complex; 490 (6.24%) Gram-negative bacilli were resistant to colistin, of which 399 were classified as Klebsiella pneumoniae (81.43%), 29 as A. baumannii complex (5.92%), 19 as E. coli (3.88%), 19 as Enterobacter cloacae (3.88%), 18 as Pseudomonas aeruginosa (3.67%), 3 as Citrobacter freundii (0.61%), 2 as Klebsiella aerogenes (0.41%), and 1 as Citrobacter youngae (0.20%)
All 490 colistin-resistant isolates were submitted to PCR for mcr gene screening, and mcr-1 was detected in eight E. coli isolates, corresponding to 1.63% of all colistin resistant Gram-negative bacilli, and to 42% of all E. coli isolates recovered in the hospital during the study. mcr-1 was not detected in any other colistinresistant species
Summary
Multidrug-resistant Gram-negative bacterial clinical isolates are responsible for high mortality rates worldwide (Agência Nacional de Vigilância Sanitária, 2016; De Waele et al, 2020), and constitute a challenge for healthcare professionals with respect to therapy choice, because few options are currently available. Isolates that are resistant to antibiotics that have been recently produced by Genomic Characterization of mcr-1.1-Producing E. coli the pharmaceutical industry have already been reported (Wang et al, 2020). These new antibiotics have no activity against carbapenem-resistant Acinetobacter baumannii (Zhanel et al, 2013; Nelson et al, 2017; Shields et al, 2017; Rodriguez et al, 2018; Noval et al, 2020). The increase of clinical use of polymyxins has been associated with elevation of the resistance rates for antibiotics of this class (Lee et al, 2015; Girardello et al, 2017; Rossi et al, 2017a; Braun et al, 2018; Zavascki et al, 2018). The molecular mechanism of polymyxins resistance involves two component systems, which regulate modifications in the bacterial membranes, reducing the negative charge of bacterial surface, and decreasing the interaction between polymyxins and bacterial cell (Moffatt et al, 2019)
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