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Use Of English By Mark Harrison.pdf

Concerted evolution of antibiotic resistance has occurred in multiple bacterial species, notably E. coli, V. cholerae, M. tuberculosis, S. pneumoniae, M. leprae, and H. pylori 67 , in part to reflect the strong selective pressures associated with antibiotics use 68 . In E. coli, strains that can survive high antibiotic concentrations demonstrate widespread cross-resistance to a wider variety of antibiotics than drug-susceptible strains 69 and strains that naturally produce carbapenemases are additionally resistant to most β-lactams 70 . Although cross-resistances have been documented between mec-MRSA and a range of antibiotics 71 , to our knowledge the emergence of this phenotype has only been observed between human-adapted ST612 isolates and ciprofloxacin. Indeed, in the light of these findings, it is remarkable that the ST612 strains observed in this study are already resistant to multiple non-β-lactam antibiotics, including meropenem, aminoglycosides, and quinolones. Intriguingly, these strains are also ciprofloxacin-resistant and mecC-MRSA has previously been shown to provide protection from ciprofloxacin 72 , suggesting that this protective effect is not mediated by ciprofloxacin targets in the bacterium. Additionally, analysis of clinical isolates from a cohort of E. coli bloodstream infections in the UK from 2011-2015 showed that the presence of the MRSA ST612 complex is associated with resistance to all antibiotics tested except tigecycline, in both HA-MRSA and CA-MRSA strains, in contrast to the situation elsewhere in the world 4, 69 , and E. coli ST612 isolates also appear less likely to acquire resistance to ciprofloxacin through mutations in the gyrA, gyrB and parC, parE genes than other STs 68, 69 . These findings support the notion that ST612 strains have evolved to be preferentially resistant to all non-β-lactam antibiotics, regardless of their mechanism of action. That the reservoir for this novel phenotype is a zoonotic CA-MRSA suggests that, in the absence of further selection, the ST612 population may revert to the status of an HA-MRSA strain in the human population; further monitoring of the ST612 complex as part of sentinel surveillance is needed to understand whether this is indeed the case.

Use Of English By Mark Harrison.pdf


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