Dual Regulation of the Small RNA MicC and the Quiescent Porin OmpN in Response to Antibiotic Stress in Escherichia coli

Dam, Sushovan; Pagès, Jean‐Marie; Masi, Muriel

doi:10.3390/antibiotics6040033

Cited by 22 publications

(16 citation statements)

References 68 publications

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“…In E. coli, expression of the OmpK35 and OmpK36 homologs, OmpF and OmpC, respectively, is regulated so as to have one or the other (but not both) expressed at high levels (68). This switching between expression of the major porins is regulated by small RNAs which can be dysregulated in the presence of ␤-lactam drugs (69). While little is known about the regulation of expression of ompK35, ompK36, ompK37, and ompK38 in K. pneumoniae, a study in Klebsiella aerogenes shows that overexpression of the small RNAs MicF and MicC can suppress expression of omp35 and omp36, respectively (70).…”

Section: Discussionmentioning

confidence: 99%

Global Trends in Proteome Remodeling of the Outer Membrane Modulate Antimicrobial Permeability in Klebsiella pneumoniae

Rocker

Lacey

Belousoff

et al. 2020

mBio

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In Gram-negative bacteria, the permeability of the outer membrane governs rates of antibiotic uptake and thus the efficacy of antimicrobial treatment. Hydrophilic drugs like β-lactam antibiotics depend on diffusion through pore-forming outer membrane proteins to reach their intracellular targets. In this study, we investigated the distribution of porin genes in more than 2,700 Klebsiella isolates and found a widespread loss of OmpK35 functionality, particularly in those strains isolated from clinical environments. Using a defined set of outer-membrane-remodeled mutants, the major porin OmpK35 was shown to be largely responsible for β-lactam permeation. Sequence similarity network analysis characterized the porin protein subfamilies and led to discovery of a new porin family member, OmpK38. Structure-based comparisons of OmpK35, OmpK36, OmpK37, OmpK38, and PhoE showed near-identical pore frameworks but defining differences in the sequence characteristics of the extracellular loops. Antibiotic sensitivity profiles of isogenic Klebsiella pneumoniae strains, each expressing a different porin as its dominant pore, revealed striking differences in the antibiotic permeability characteristics of each channel in a physiological context. Since K. pneumoniae is a nosocomial pathogen with high rates of antimicrobial resistance and concurrent mortality, these experiments elucidate the role of porins in conferring specific drug-resistant phenotypes in a global context, informing future research to combat antimicrobial resistance in K. pneumoniae. IMPORTANCE Klebsiella pneumoniae is a pathogen of humans with high rates of mortality and a recognized global rise in incidence of carbapenem-resistant K. pneumoniae (CRKP). The outer membrane of K. pneumoniae forms a permeability barrier that modulates the ability of antibiotics to reach their intracellular target. OmpK35, OmpK36, OmpK37, OmpK38, PhoE, and OmpK26 are porins in the outer membrane of K. pneumoniae, demonstrated here to have a causative relationship to drug resistance phenotypes in a physiological context. The data highlight that currently trialed combination treatments with a carbapenem and β-lactamase inhibitors could be effective on porin-deficient K. pneumoniae. Together with structural data, the results reveal the role of outer membrane proteome remodeling in antimicrobial resistance of K. pneumoniae and point to the role of extracellular loops, not channel parameters, in drug permeation. This significant finding warrants care in the development of phage therapies for K. pneumoniae infections, given the way porin expression will be modulated to confer phage-resistant—and collateral drug-resistant—phenotypes in K. pneumoniae.

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Section: Discussionmentioning

confidence: 99%

Global Trends in Proteome Remodeling of the Outer Membrane Modulate Antimicrobial Permeability in Klebsiella pneumoniae

Rocker

Lacey

Belousoff

et al. 2020

mBio

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“…Four Ec ST410 clinical isolates came from the Microbiological collection of the Public Health Faculty of the Lebanese University (Tripoli, Lebanon) and three ST410 isolates of animal origin from the ANSES strain collection. Test for OmpC permeability to β-lactam was performed in strain W3110 deleted for ompC and ompF genes 49 . Antibiotic susceptibility was performed by the disk diffusion method following the Clinical & Laboratory Standards Institute (CLSI) guidelines 32 or by Etest (Biomérieux) following the manufacturer’s recommendations.…”

Section: Methodsmentioning

confidence: 99%

Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producingEscherichia coli

Patiño-Navarrete

Rosinski‐Chupin

Cabanel

et al. 2018

Preprint

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26Carbapenem-resistant Enterobacteriaceae are considered by WHO as "critical" priority 27 pathogens for which novel antibiotics are urgently needed. The dissemination of 28 carbapenemase-producing Escherichia coli (CP-Ec) in the community is a major public 29 health concern. However, the global molecular epidemiology of CP-Ec isolates, as well as 30 the genetic bases for the emergence and global dissemination of specific lineages, 31 remain largely unknown. Here, by combining a thorough genomic and evolutionary 32 analysis of Ec ST410 isolates with a broad analysis of 12,584 E. coli and Shigella 33 genomes, we showed that the fixation of carbapenemase genes depends largely on a 34 combination of mutations in ftsI encoding the penicillin binding protein 3 and in the 35 porin genes ompC and ompF. Mutated ftsI genes and a specific ompC allele inducing 36 reduced susceptibility to diverse β-lactams spread across the species by recombination. 37The selection of CP-Ec lineages able to disseminate is more complex than the mere 38 acquisition of carbapenemase genes. 39 40 41 Antibiotic resistance is one of the most urgent public health concerns. The 42 increasing rate in antimicrobial resistances worldwide suggests a bleak outlook in terms 43 of morbidity, mortality and economic loss 1 . Carbapenems are one of the last resort 44 antibiotics used to treat infections caused by multidrug-resistant (MDR) Gram-negative 45 bacteria 2 . Dissemination of carbapenem-resistant Enterobacteriaceae (CRE) threatens 46 the efficacy of current treatment options. Carbapenem-resistance may result from a 47 combination of mutations leading to reduced permeability (e.g. porin deficiency) and 48 overexpression of an extended-spectrum β-lactamase (ESBL) or a cephalosporinase that 49 show a weak activity against carbapenems 3 . However, the main resistance mechanism is 50 the acquisition of a carbapenemase gene 4 . The major carbapenemases encountered in 51Enterobacteriaceae belong to Ambler class A (KPC-type), class B (metallo-β-lactamases 52 IMP, VIM-and NDM-types) or class D (OXA-48-like enzymes) 5 . As these carbapenemases 53 are now frequently encountered in Escherichia coli, carbapenemase-producing E. coli 54 (CP-Ec) might follow the same expansion and dissemination in hospitals and the 55 community as the one observed for CTX-M-type ESBL-producing E. coli isolates 6,7 . A 56 scenario feared by public health authorities. This is especially worrisome as these 57 isolates are usually resistant to multiple antibiotics. 58The epidemiology of CP-Ec is complex with geographical diversity in terms of 59 carbapenemase genes and of dominant lineages 4 . Most studies performed at national or 60 hospital levels point to a broad diversity of isolates as defined by multilocus sequence 61 typing (MLST), with some isolates belonging to a few dominant sequence types (STs) 62 like ST38, clonal complex (CC) 10 (ST10, ST167, ST617), ST101, ST131 and ST410 that 63 express different carbapenemases 4,[8][9][10][11][12][13][14] . However, their prevalence vari...

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“…Porins are post-transcriptionally regulated by a variety of sRNAs in addition to MicF. These include such as MicC, IpeX, CyaR, and RybB [8,9]. Two other phosphorylation systems, i.e., CpxA-CpxR and ArcA-ArcB, control OmpC and OmpF proteins [10,11].…”

Section: Introductionmentioning

confidence: 99%

Effect of photooxidative stress and mannitol on synthesis of OmpC-OmpF proteins of Escherichia coli in lake water

Darcan

Aktop

2019

Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi

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Bu çalışma göl suyunda Escherichia coli'nin OmpC ve OmpF porinlerinin sentezi üzerine fotooksidatif stres ve mannitolün etkisini araştırmıştır. OmpF sentezi fotooksidatif stresden bağımsız bir şekilde azalırken, OmpC sentezi göl suyunda fotooksidatif stresin bir sonucu olarak azalmıştır. Bu nedenle E. coli'de OmpC sentezi fotooksidatif stresden direkt olarak etkilenir. envZ ve pta genleri mutasyonların göl suyunda fotooksidatif stres altında E. coli'de OmpC ve OmpF sentezinin kontrolü üzerine bir etkisi yoktur. Mannitol fotooksidatif stresden korumayı sağlayan bir antioksidant maddedir. Bu çalışmada OmpF sentezinin fotooksidatif stresden bağımsız bir şekilde azaldığını ancak OmpC sentezindeki azalmanın yabani tip E. coli'de fotooksidatif stres bağımlı olduğu bulunmuştur. OmpC sentezi bilinmeyen bir mekanizma ile fotooksidatif stres ile düzenlenmektedir. Mannitol porin sentezinin kontrolünde EnvZ ile bir ilişkiye sahiptir.

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Dual Regulation of the Small RNA MicC and the Quiescent Porin OmpN in Response to Antibiotic Stress in Escherichia coli

Cited by 22 publications

References 68 publications

Global Trends in Proteome Remodeling of the Outer Membrane Modulate Antimicrobial Permeability in Klebsiella pneumoniae

Global Trends in Proteome Remodeling of the Outer Membrane Modulate Antimicrobial Permeability in Klebsiella pneumoniae

Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producingEscherichia coli

Effect of photooxidative stress and mannitol on synthesis of OmpC-OmpF proteins of Escherichia coli in lake water

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