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=Volume 12 - 2021

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=Treatment strategies of infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) are limited. Fosfomycin, a broad-spectrum antibiotic, has attracted renewed interest in combination therapy to fight K. pneumoniae infections. However, reports on fosfomycin-resistant K. pneumoniae are increasing. Among the 57 CRKP strains, 40 (70.2%) were resistant to fosfomycin. Thus, whole genome sequencing and bioinformatic analysis was conducted to reveal molecular characteristics of fosfomycin-resistant K. pneumoniae. Twenty-three isolates co-harbored fosAkp and fosA3, with KPC-producing ST11-KL64-wzi64-O2 (n = 13) and ST11-KL47-wzi209-OL101 (n = 8), the predominating clonal groups, while fosA3 was not detected in isolates carrying class B carbapenemase genes. Twenty-two (out of 26) ST11-KL64 strains were positive of rmpA2, of which 12 carried fosA3. Four of the 23 fosA3-positive isolates could successfully transfer their fosfomycin-resistant determinants to Escherichia coli J53AziR. All the four strains belonged to ST11-KL47 with the same pulse 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) co-harbouring fosA3, blaKPC-2, blaCTX-M-65, blaSHV-12, rmtB and blaTEM-1 was identified. ST11-KL64 and ST11-KL47 K. pneumoniae, with higher resistance and virulence should be critically monitored to prevent the future dissemination of resistance.