Transmissible silver resistance readily evolves in high-risk clone isolates of Klebsiella pneumoniae

Abstract

Silver is used extensively in both hospitals and outpatient clinics as a disinfectant coating agent on various devices. Resistance to silver was recently reported as an emerging problem in Enterobacteriaceae. Multidrug-resistant high-risk clones of Klebsiella pneumoniae are common causes of serious healthcare-associated infections worldwide posing a serious threat to patients. In this study, we investigated the capacity of both high-risk (CG14/15 and CG258) and minor clone strains of K. pneumoniae to develop resistance to silver. Resistance was induced in vitro in silver-susceptible but otherwise multidrug-resistant clinical isolates. Genetic alterations in the silver-resistant derivative strains with regard to the silver-susceptible isolates were investigated by whole-genome sequencing. The transferability of high-level resistance to silver was also tested. We demonstrated that the high-level resistance to silver can quickly evolve as a consequence of a single-point mutation either in the cusS gene of the chromosomally encoded CusCFBARS efflux system and/or in the silS gene of the plasmid-encoded Copper Homeostasis and Silver Resistance Island (CHASRI) coding also for a metallic efflux. The minimal inhibitory concentrations (MICs) of the strains increased from 4 mg/L (23.5 μM) AgNO to >8,500 mg/L (>50,000 μM) AgNO during induction. Harboring the CHASRI proved an important selective asset for K. pneumoniae when exposed to silver. Successful conjugation experiments using Escherichia coli K12 J5-3 as recipient showed that high-level silver resistance can transmit between strains of high-risk clones of K. pneumoniae (ST15 and ST11) and isolates from additional species of Enterobacteriaceae. The lack of fitness cost associated with the carriage of the CHASRI in a silver-free environment and the presence of the RelEB toxin-antitoxin system on the conjugative plasmids could advance the dissemination of silver resistance. Our results show that multidrug-resistant high-risk clones of K. pneumoniae are capable of evolving and transmitting high-level resistance to silver. This observation should warrant a more judicious use of silver coated-devices to prevent the extensive dissemination of silver resistance.

Plasmid diversity among genetically related Klebsiella pneumoniae blaKPC-2 and blaKPC-3 isolates collected in the Dutch national surveillance

“…The small plasmids contained putative virulence determinants. The presence of these systems may contribute to the success of transmission of specific K. pneumoniae strains in the hospital setting or the community 13 , 29 , 30 . Escherichia RCS47 prophage sequences were found on medium and large plasmids in the cluster isolates analyzed.…”

<p>The increasing threat of silver-resistance in clinical isolates from wounds and burns</p>

“…Staehlin and colleagues12 have described a heavy metal homeostasis/resistance island, named as Copper homeostasis and silver resistance island (CHASRI), which was assembled and dispersed within members of Enterobacteriaceae family. Recently, CHASRI was found to be equally distributed in the plasmids and chromosomes of Enterobacteriaceae and was able to provide silver-resistance after mutation in Cus S and/or sil S genes of the CHASRI island 13…”

Characterization of Silver Resistance and Coexistence of sil Operon with Antibiotic Resistance Genes Among Gram-Negative Pathogens Isolated from Wound Samples by Using Whole-Genome Sequencing

“…MLST analysis showed that silver resistance can be induced within K. pneumoniae strains belonged to both high-risk group (ST11 and ST15) and minor clone groups, which is in line with previous study. 14 …”

“…Relative change in the fitness cost of Ag + resistance was determined by growth curves between the susceptible parent strains and the corresponding mutants. 14 …”