Reduced Chlorhexidine Susceptibility Is Associated with Tetracycline Resistance tet Genes in Clinical Isolates of Escherichia coli

Abstract

Chlorhexidine is a widely used antiseptic in hospital and community healthcare. Decreased susceptibility to this compound has been recently described in Klebsiella pneumoniae and Pseudomonas aeruginosa , together with cross-resistance to colistin. Surprisingly, few data are available for Escherichia coli , the main species responsible for community and healthcare-associated infections. In order to decipher chlorhexidine resistance mechanisms in E. coli , we studied both in vitro derived and clinical isolates through whole-genome sequence analysis. Comparison of strains grown in vitro under chlorhexidine pressure identified mutations in the gene mlaA coding for a phospholipid transport system. Phenotypic analyses of single-gene mutant from the Keio collection confirmed the role of this mutation in the decreased susceptibility to chlorhexidine. However, mutations in mlaA were not found in isolates from large clinical collections. In contrast, genome wide association studies (GWAS) showed that, in clinical strains, chlorhexidine reduced susceptibility was associated with the presence of tetA genes of class B coding for efflux pumps and located in a Tn 10 transposon. Construction of recombinant strains in E. coli K-12 confirmed the role of tetA determinant in acquired resistance to both chlorhexidine and tetracycline. Our results reveal two different evolutionary paths leading to chlorhexidine decreased susceptibility: one restricted to in vitro evolution conditions and involving a retrograde phospholipid transport system; the other observed in clinical isolates associated with efflux pump TetA. None of these mechanisms provides cross-resistance to colistin. This work demonstrates the GWAS power to identify new resistance mechanisms in bacterial species.

Benchmarking AI-based plasmid annotation tools for antibiotic resistance genes mining from metagenome of the Virilla River, Costa Rica

“…These ARGs have been demonstrated to also be ubiquitous in the chromosomal genomes [37], elucidating the idea of their integration into the chromosomes of the metagenome. In addition, the presence of tetracycline resistance could be associated with biocide-reduced susceptibility [38], unifying the presence of both ARGs annotation into metagenomic chromosomes and absence in plasmidomes. Finally, the same pattern is reported for genes related to glycopeptide resistance, including those annotated in our metagenome but not in the plasmidomes [39].…”

Identification and comparison of somatic antigen composition for bacteria from Providencia genus

“…It enabled P. rettgeri strain BML2496 to establish the resistance to tetracycline [32]. TetD gene encodes a transcription regulator [33]. TetA is responsible for the synthesis of the tetracycline efflux MFS transporter [34].…”

Resistance mechanisms for Gram-negative bacteria-specific lipopeptides, turnercyclamycins, differ from that of colistin

“…In contrast to polymyxins for which resistant strains are readily selected ( 46 , 47 ), it was more difficult to obtain resistant mutants to turnercyclamycins, especially to turnercyclamycin A. Turnercyclamycin B-resistant strains shared mutations in mlaA , which is involved in the retrograde trafficking of mislocalized phospholipids from the OM to the IM ( 40 , 41 ). MlaA is not known to directly interact with an antibiotic or to be involved in antibiotic resistance ( 48 – 51 ). In a previous study of A. baumannii colistin resistance, the co-deletion of LPS/LOS biosynthesis and mlaA showed greatly increased resistance in comparison to LPS/LOS loss alone ( 52 ).…”