AUTHOR=Hao Yingying , Zhao Xuguang , Zhang Cui , Bai Yuanyuan , Song Zhen , Lu Xinglun , Chen Ran , Zhu Yaoyao , Wang Yueling 

TITLE=Clonal Dissemination of Clinical Carbapenem-Resistant Klebsiella pneumoniae Isolates Carrying fosA3 and blaKPC–2 Coharboring Plasmids in Shandong, China

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.771170

DOI=10.3389/fmicb.2021.771170

ISSN=1664-302X

ABSTRACT=<p>Treatment strategies of infection by carbapenem-resistant <italic>Klebsiella pneumoniae</italic> (CRKP) are limited. Fosfomycin, a broad-spectrum antibiotic, has attracted renewed interest in combination therapy to fight <italic>K. pneumoniae</italic> infections. However, reports on fosfomycin-resistant <italic>K. pneumoniae</italic> are increasing. Among the 57 CRKP strains, 40 (70.2%) were resistant to fosfomycin. Thus, whole-genome sequencing and bioinformatics analysis were conducted to reveal molecular characteristics of fosfomycin-resistant <italic>K. pneumoniae</italic>. Twenty-three isolates coharbored <italic>fosA</italic><italic><sup>kp</sup></italic> and <italic>fosA3</italic>, with <italic>K. pneumoniae</italic> carbapenemase (KPC)-producing ST11-KL64-wzi64-O2 (<italic>n</italic> = 13) and ST11-KL47-wzi209-OL101 (<italic>n</italic> = 8), the predominating clonal groups, while <italic>fosA3</italic> was not detected in isolates carrying class B carbapenemase genes. Twenty-two (out of 26) ST11-KL64 strains were positive for <italic>rmpA2</italic>, of which 12 carried <italic>fosA3</italic>. Four of the 23 <italic>fosA3</italic>-positive isolates could successfully transfer their fosfomycin-resistant determinants to <italic>Escherichia coli</italic> J53Azi<italic><sup>R</sup></italic>. All four strains belonged to ST11-KL47 with the same pulsed-field gel electrophoresis profile, and their transconjugants acquired fosfomycin, carbapenem, and aminoglycoside resistance. A 127-kb conjugative pCT-KPC-like hybrid plasmid (pJNKPN52_KPC_fosA) coharboring <italic>fosA3</italic>, <italic>bla</italic><sub><italic>KPC</italic>–2</sub>, <italic>bla</italic><sub><italic>CTX–M</italic>–65</sub>, <italic>bla</italic><sub><italic>SHV</italic>–12</sub>, <italic>rmtB</italic>, and <italic>bla</italic><sub><italic>TEM</italic>–1</sub> was identified. ST11-KL64 and ST11-KL47 <italic>K. pneumoniae</italic>, with higher resistance and virulence, should be critically monitored to prevent the future dissemination of resistance.</p>