Mutations in the gene liaF, part of the LiaFSR complex, involved in cell envelope
stress response, are known to cause daptomycin resistance (DAP-R) in Enterococcus
faecium, which can complicate the treatment of vancomycin-resistant enterococcal
infections. We recently described a case of isolation of a treatment-emergent DAP-R
VREm occurring in the context of combined daptomycin and ampicillin treatment in a
liver transplant patient. On initial WGS data analysis, a large deletion in the liaFSR
complex region was suggested. More recently, in vitro deletions in liaR, the
regulator gene of the complex, are shown to restore susceptibility to daptomycin and
telavancin in VRE E. faecalis, increase the rate of killing by human antimicrobial
peptides, and attenuate virulence in an animal model. We therefore questioned
whether Australian VRE have different genetic context under antibiotic pressure to
develop daptomycin resistance, and explored if a deletion of the LiaFSR complex was
present in Australian VRE isolates.
3 Clinical isolates, (2 being daptomycin-non- susceptible) and 94 sequential VRE
strains isolated from screening inpatients from an Australian tertiary hospital
underwent detection of liaF with real-time PCR.
Of the screening isolates, 48 of these carried the vanA gene, and 46 carried vanB.
The liaF gene was detected in 100% of the 94 isolates using RT-PCR, and detected
also in the clinical isolates.
The LiaFSR complex is found in all genrea clinically important Gram-positive bacteria,
including Streptococci, Bacillus, and Staphylococcus. It’s involved in stress response
of the cell membrane to attack by antimicrobial peptides, which have similar action
to calcium-complexed daptomycin. In vitro deletions of this complex in Enterococcus
faecalis have shown to alter daptomycin susceptibility.
On re-analysis of the WGS data from the initial isolate, alternate software was used
and liaFSR genes were normal. Assessment of a large number of sequentially stored
isolates did not find any with this deletion. It is important to confirm unusual findings
from WGS analysis using alternate methods and consider re-doing analyses using
different software.