Abstract
The major international sequence types/lineages of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae and ESBL-producing E. coli were demonstrated to have been advanced by favorable fitness balance associated with high-level resistance to fluoroquinolones. The paper shows that favorable fitness in the major STs/lineages of these pathogens was principally attained by the capacity of evolving mutations in the fluoroquinolone-binding serine residues of both the DNA gyrase and topoisomerase IV enzymes. The available information on fitness balance incurred by individual and various combinations of mutations in the enzymes is reviewed in multiple species. Moreover, strong circumstantial evidence is presented that major STs/lineages of other multi-drug resistant bacteria, primarily vancomycin-resistant Enterococcus faecium (VRE), emerged by a similar mechanism. The reason(s) why the major ST/lineage strains of various pathogens proved more adept at evolving favorable mutations than most isolates of the same species remains to be elucidated.
Highlights
It is well-established that major international clones and lineages of various multi-drug resistant hospital-associated pathogens emerged during the past three decades
We have been witnessing a dramatic expansion of some global clones/lineages of methicillin-resistant Staphylococcus aureus (MRSA) (Nübel et al, 2011; Grundmann et al, 2014), extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (Damjanova et al, 2008; Holt et al, 2015), ESBL-producing E. coli (Pitout and DeVinney, 2017), Clostridium difficile (He et al, 2013), and vancomycin-resistant Enterococcus faecium (VRE) (Willems et al, 2005) among others
Recent reports investigating the fitness cost associated with resistance to fluoroquinolones in MRSA, ESBL-producing K. pneumoniae, ESBL-producing E. coli and Double-Serine quinolone resistance-determining regions (QRDRs) Mutations Promote Clones
Summary
It is well-established that major international clones and lineages of various multi-drug resistant hospital-associated pathogens emerged during the past three decades. While minor clone/lineage strains of MRSA, ESBL-producing K. pneumoniae, ESBL-producing E. coli and C. difficile suffer considerable fitness cost upon developing high-level resistance to fluoroquinolones the major clone isolates retain most of their vitality allowing to achieve dominance in facilities where fluoroquinolones are in extensive use (Horváth et al, 2012; Knight et al, 2012; Holden et al, 2013; Tóth et al, 2014; Johnson et al, 2015; Wasels et al, 2015). The question concerns the mechanism: in what respect do the major clone strains of MRSA, ESBL-producing K. pneumoniae, ESBL-producing E. coli and C. difficile differ from minor clone isolates that permits the preservation of fitness even at high levels of resistance to fluoroquinolones?
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