Heteroduplex analysis of regulatory mutations and of insertions (IS1, IS2, IS5) in the bipolar argECBH operon of Escherichia coli

1978 ◽  
Vol 161 (2) ◽  
pp. 175-184 ◽  
Author(s):  
D. Charlier ◽  
M. Crabeel ◽  
S. Palchaudhuri ◽  
R. Cunin ◽  
A. Boyen ◽  
...  
1973 ◽  
Vol 114 (2) ◽  
pp. 469-473 ◽  
Author(s):  
Noé Zwaig ◽  
Rosa Nagel de Zwaig ◽  
Tomás Istúriz ◽  
Magda Wecksler

2021 ◽  
Author(s):  
Maryam Alzayn ◽  
Punyawee Dulyayangkul ◽  
Naphat Satapoomin ◽  
Kate J Heesom ◽  
Matthew B Avison

Cefalexin is a widely used 1st generation cephalosporin, and resistance in Escherichia coli is caused by Extended-Spectrum (e.g. CTX-M) and AmpC β-lactamase production and therefore frequently coincides with 3rd generation cephalosporin resistance. However, we have recently identified large numbers of E. coli isolates from human infections, and from cattle, where cefalexin resistance is not β-lactamase mediated. Here we show, by studying laboratory selected mutants, clinical isolates, and isolates from cattle, that OmpF porin disruption or downregulation is a major cause of cefalexin resistance in E. coli. Importantly, we identify multiple regulatory mutations that cause OmpF downregulation. In addition to mutation of ompR, already known to downregulate OmpF and OmpC porin production, we find that rseA mutation, which strongly activates the Sigma E regulon, greatly increasing DegP production, which degrades OmpF, OmpC and OmpA porins. Furthermore, we reveal that mutations affecting lipopolysaccharide structure, exemplified by the loss of GmhB, essential for lipopolysaccharide heptosylation, also modestly activate DegP production, resulting in OmpF degradation. Remarkably, given the critical importance attached to such systems for normal E. coli physiology, we find evidence for DegP-mediated OmpF downregulation, gmhB and rseA loss of function mutation in E. coli isolates derived from human infections. Finally, we show that these regulatory mutations enhance the ability of group 1 CTX-M β-lactamase to confer reduced carbapenem susceptibility, particularly those mutations that cause OmpC in addition to OmpF downregulation.


2009 ◽  
Vol 191 (12) ◽  
pp. 4025-4029 ◽  
Author(s):  
Thomas Ferenci ◽  
Zhemin Zhou ◽  
Thu Betteridge ◽  
Yan Ren ◽  
Yu Liu ◽  
...  

ABSTRACT The genome of an Escherichia coli MC4100 strain with a λ placMu50 fusion revealed numerous regulatory differences from MG1655, including one that arose during laboratory storage. The 194 mutational differences between MC4100(MuLac) and other K-12 sequences were mostly allocated to specific lineages, indicating the considerable mutational divergence between K-12 strains.


1976 ◽  
Vol 128 (1) ◽  
pp. 39-48 ◽  
Author(s):  
C Legrain ◽  
V Stalon ◽  
N Glansdorff ◽  
D Gigot ◽  
A Piéard ◽  
...  

Author(s):  
Maryam Alzayn ◽  
Punyawee Dulyayangkul ◽  
Naphat Satapoomin ◽  
Kate J. Heesom ◽  
Matthew B. Avison

Cefalexin is a widely used 1 st generation cephalosporin, and resistance in Escherichia coli is caused by Extended-Spectrum (e.g., CTX-M) and AmpC β-lactamase production and therefore frequently coincides with 3 rd generation cephalosporin resistance. However, we have recently identified large numbers of E. coli isolates from human infections, and from cattle, where cefalexin resistance is not β-lactamase mediated. Here we show, by studying laboratory selected mutants, clinical isolates, and isolates from cattle, that OmpF porin disruption or downregulation is a major cause of cefalexin resistance in E. coli . Importantly, we identify multiple regulatory mutations that cause OmpF downregulation. In addition to mutation of ompR , already known to downregulate OmpF and OmpC porin production, we find that rseA mutation, which strongly activates the Sigma E regulon, greatly increasing DegP production, which degrades OmpF, OmpC and OmpA. Furthermore, we reveal that mutations affecting lipopolysaccharide structure, exemplified by the loss of GmhB, essential for lipopolysaccharide heptosylation, also modestly activate DegP production, resulting in OmpF degradation. Remarkably, given the critical importance attached to such systems for normal E. coli physiology, we find evidence for DegP-mediated OmpF downregulation, gmhB and rseA loss of function mutation in E. coli isolates derived from human infections. Finally, we show that these regulatory mutations enhance the ability of group 1 CTX-M β-lactamase to confer reduced carbapenem susceptibility, particularly those mutations that cause OmpC in addition to OmpF downregulation.


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