scholarly journals Identification of fosA10, a Novel Plasmid-Mediated Fosfomycin Resistance Gene of Klebsiella pneumoniae Origin, in Escherichia coli

2020 ◽  
Vol Volume 13 ◽  
pp. 1273-1279 ◽  
Author(s):  
Ying Huang ◽  
Qingqing Lin ◽  
Qiaoli Zhou ◽  
Luchao Lv ◽  
Miao Wan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Resistance Gene ◽  
Fosfomycin Resistance

scholarly journals Structure and Dynamics of FosA-Mediated Fosfomycin Resistance in Klebsiella pneumoniae and Escherichia coli

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Erik H. Klontz ◽  
Adam D. Tomich ◽  
Sebastian Günther ◽  
Justin A. Lemkul ◽  
Daniel Deredge ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Molecular Dynamics ◽  
Klebsiella Pneumoniae ◽  
Crystal Structures ◽  
Active Sites ◽  
Content Type ◽  
Dimer Interface ◽  
Fosfomycin Resistance ◽  
Gram Negative Organisms ◽  
Dynamics Simulations

ABSTRACT Fosfomycin exhibits broad-spectrum antibacterial activity and is being reevaluated for the treatment of extensively drug-resistant pathogens. Its activity in Gram-negative organisms, however, can be compromised by expression of FosA, a metal-dependent transferase that catalyzes the conjugation of glutathione to fosfomycin, rendering the antibiotic inactive. In this study, we solved the crystal structures of two of the most clinically relevant FosA enzymes: plasmid-encoded FosA3 from Escherichia coli and chromosomally encoded FosA from Klebsiella pneumoniae (FosAKP). The structure, molecular dynamics, catalytic activity, and fosfomycin resistance of FosA3 and FosAKP were also compared to those of FosA from Pseudomonas aeruginosa (FosAPA), for which prior crystal structures exist. E. coli TOP10 transformants expressing FosA3 and FosAKP conferred significantly greater fosfomycin resistance (MIC, >1,024 μg/ml) than those expressing FosAPA (MIC, 16 μg/ml), which could be explained in part by the higher catalytic efficiencies of the FosA3 and FosAKP enzymes. Interestingly, these differences in enzyme activity could not be attributed to structural differences at their active sites. Instead, molecular dynamics simulations and hydrogen-deuterium exchange experiments with FosAKP revealed dynamic interconnectivity between its active sites and a loop structure that extends from the active site of each monomer and traverses the dimer interface. This dimer interface loop is longer and more extended in FosAKP and FosA3 than in FosAPA, and kinetic analyses of FosAKP and FosAPA loop-swapped chimeric enzymes highlighted its importance in FosA activity. Collectively, these data yield novel insights into fosfomycin resistance that could be leveraged to develop new strategies to inhibit FosA and potentiate fosfomycin activity.

scholarly journals Detection of the plasmid-encoded fosfomycin resistance gene fosA3 in Escherichia coli of food-animal origin

2012 ◽  
Vol 68 (4) ◽  
pp. 766-770 ◽  
Author(s):  
J. Hou ◽  
X. Yang ◽  
Z. Zeng ◽  
L. Lv ◽  
T. Yang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Resistance Gene ◽  
Animal Origin ◽  
Food Animal ◽  
Fosfomycin Resistance

scholarly journals Inoculum size effects in blaIMP-6 and plasmid-mediated quinolone resistance gene-positive Enterobacteriaceae in Japan

2019 ◽  
Author(s):  
Yoshihiko Ogawa ◽  
Ryuichi Nakano ◽  
Kei Kasahara ◽  
Tomoki Mizuno ◽  
Nobuyasu Hirai ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Drug Resistance ◽  
Klebsiella Pneumoniae ◽  
Size Effect ◽  
Resistance Gene ◽  
Size Effects ◽  
Antimicrobial Agents ◽  
Inoculum Size ◽  
Experimental Strains

AbstractThe aim of this study was to examine the resistance genes in clinical isolates which produced IMP-6 type metallo-β-lactamase lactamase (MBL) and had mildly reduced susceptibilities to levofloxacin and/or amikacin. The inoculum size effect was also assessed. A total of 14 Enterobacteriaceae isolates (2 Escherichia coli and 12 Klebsiella pneumoniae) which produced IMP-6 MBL, and had mild increases in their MICs for levofloxacin and amikacin were examined. Thirteen out of 14 isolates harbored CTX-M-2, with the remaining isolate co-harboring CTX-M-2 and CTX-M-1 as ESBLs. All isolates carried one or more PMQRs; aac(6′)-Ib-cr was the most prevalent (92.8%), followed by oqxA (64.3%), qnrS (42.9%), oqxAB (21.4%), and qnrB (14.3%). The inoculum size effects were significant in all strains for meropenem, 13 for imipenem, 7 for levofloxacin, and 3 for amikacin. Conjugation was successfully performed with 8 isolates and 11 strains were obtained. Eleven of the experimental strains (100%), and 8 strains (72.7%) showed inoculum size effects for meropenem and imipenem, respectively. No inoculum size effect was seen for levofloxacin. Four strains harbored qnr genes and 2 strains harbored qnr genes and QRDR mutations concurrently. blaIMP-6 positive Enterobacteriaceae with mildly reduced susceptibilities to levofloxacin and/or amikacin also harbored at least one plasmid-mediated drug resistance gene. These represent an unrecognized threat, capable of compromising the in vitro activity of many classes of antimicrobial agents. We conclude that IMP-6 MBL plays an important role in decreasing the MIC for carbapenems, whereas qnr does not for levofloxacin.

scholarly journals Plasmid-mediated colistin resistance gene mcr-1 in Escherichia coli and Klebsiella pneumoniae isolated from market retail fruits in Guangzhou, China

2019 ◽  
Vol Volume 12 ◽  
pp. 385-389 ◽  
Author(s):  
Fan Yang ◽  
Cong Shen ◽  
Xiaobin Zheng ◽  
Yan Liu ◽  
Mohamed Abd El-Gawad El-Sayed Ahmed ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Resistance Gene ◽  
Colistin Resistance

Prevalence of the colistin resistance gene mcr-1 in colistin-resistant Escherichia coli and Klebsiella pneumoniae isolated from humans in Thailand

2018 ◽  
Vol 15 ◽  
pp. 32-35 ◽  
Author(s):  
Warawan Eiamphungporn ◽  
Sakda Yainoy ◽  
Chakornpat Jumderm ◽  
Rachanis Tan-arsuwongkul ◽  
Surapee Tiengrim ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Resistance Gene ◽  
Colistin Resistance

scholarly journals Colistin resistance gene mcr-1 and pHNSHP45 plasmid in human isolates of Escherichia coli and Klebsiella pneumoniae

2016 ◽  
Vol 16 (3) ◽  
pp. 285-286 ◽  
Author(s):  
Nicole Stoesser ◽  
Amy J Mathers ◽  
Catrin E Moore ◽  
Nicholas PJ Day ◽  
Derrick W Crook
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Resistance Gene ◽  
Colistin Resistance

scholarly journals Coexistence of SFO-1 and NDM-1 β-lactamase genes and fosfomycin resistance gene fosA3 in an Escherichia coli clinical isolate

2015 ◽  
Vol 362 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Jing-yi Zhao ◽  
Yuan-qi Zhu ◽  
Yan-nian Li ◽  
Xiao-dong Mu ◽  
Li-ping You ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Resistance Gene ◽  
Clinical Isolate ◽  
Fosfomycin Resistance

Prevalence of Plasmid-Mediated Fosfomycin Resistance Gene fosA3 Among CTX-M-Producing Escherichia coli Isolates from Chickens in China

2017 ◽  
Vol 14 (4) ◽  
pp. 210-218 ◽  
Author(s):  
Wei Jiang ◽  
Shuai Men ◽  
Linghan Kong ◽  
Suzhen Ma ◽  
Yongqiang Yang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Resistance Gene ◽  
Fosfomycin Resistance
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