AUTHOR=Esposito Eliana P. , Cervoni Matteo , Bernardo Mariano , Crivaro Valeria , Cuccurullo Susanna , Imperi Francesco , Zarrilli Raffaele 

TITLE=Molecular Epidemiology and Virulence Profiles of Colistin-Resistant Klebsiella pneumoniae Blood Isolates From the Hospital Agency “Ospedale dei Colli,” Naples, Italy

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.01463

DOI=10.3389/fmicb.2018.01463

ISSN=1664-302X

ABSTRACT=<p>Resistance to colistin is increasingly reported in <italic>Klebsiella pneumoniae</italic> clinical isolates. The aim of this study was to analyze the molecular epidemiology and virulence profiles of 25 colistin-resistant <italic>K. pneumoniae</italic> blood isolates from the Hospital Agency “Ospedale dei Colli,” Naples, Italy, during 2015 and 2016. Colistin MIC values of isolates ranged from 4 to 256 mg/L. The inactivation of the <italic>mgrB</italic> gene, encoding a negative regulator of the PhoQ/PhoP signaling system, was the most frequent mechanism of colistin resistance found in 22 out of 25 isolates. Of these, 10 isolates assigned to ST512 and PFGE types A and A4 showed identical frameshift mutation and premature termination of <italic>mgrB</italic> gene; 4 isolates assigned to ST258 and PFGE types A1 showed non-sense, frameshift mutation, and premature termination; 3 and 1 isolates assigned to ST258 and PFGE A2 and ST512 and PFGE A3, respectively, had insertional inactivation of <italic>mgrB</italic> gene due to IS<italic>5</italic>-like mobile element; 2 isolates assigned to ST101 and 1 to ST392 had missense mutations in the <italic>mgrB</italic> gene, 1 isolate assigned to ST45 showed insertional inactivation of <italic>mgrB</italic> gene due to IS<italic>903</italic>-like mobile element. <italic>phoQ</italic> missense mutations were found in 2 isolates assigned to ST629 and ST101, respectively, which also showed a missense mutation in <italic>pmrA</italic> gene. The <italic>mcr-1-2-3-4</italic> genes were not detected in any isolate. Colistin-resistant <italic>K. pneumoniae</italic> isolates showed variable virulence profiles in <italic>Galleria mellonella</italic> infection assays, with the infectivity of two isolates assigned to ST45 and ST629 being significantly higher than that of all other strains (<italic>P</italic> &lt; 0.001). Interestingly, colistin MIC values proved to make a significant contribution at predicting lethal doses values (LD<sub>50</sub> and LD<sub>90</sub>) of studied isolates in <italic>G. mellonella</italic>. Our data show that MgrB inactivation is a common mechanism of colistin resistance among <italic>K. pneumoniae</italic> in our clinical setting. The presence of identical mutations/insertions in isolates of the same ST and PFGE profile suggests the occurrence of clonal expansion and cross-transmission. Although virulence profiles differ among isolates irrespective of their genotypes, our results suggest that high colistin MIC could predict lower infectivity capability of the isolates.</p>