The
            <i>Escherichia coli</i>
            Efflux Pump TolC Promotes Aggregation of Enteroaggregative
            <i>E. coli</i>
            042

Imuta, Naoko; Nishi, Junichiro; Tokuda, Koichi; Fujiyama, Rika; Manago, Kunihiro; Iwashita, Mayumi; Jav, Sarantuya; Kawano, Yoshifumi

doi:10.1128/iai.00758-07

Cited by 36 publications

(29 citation statements)

References 46 publications

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“…6A). TolC has been reported to be required for adhesion and biofilm formation in pathogenic enteroaggregative E. coli; deletion mutants have decreased aggregation and adhesion under growth conditions with high-glucose Dulbecco's minimal medium (65,66), consistent with our findings.…”

Section: Discussionsupporting

confidence: 82%

Small RNA Regulation of TolC, the Outer Membrane Component of Bacterial Multidrug Transporters

Parker

Gottesman

2016

J Bacteriol

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Bacteria use multidrug efflux pumps to export drugs and toxic compounds out of the cell. One of the most important efflux pumps in Escherichia coli is the AcrAB-TolC system. Small regulatory RNAs (sRNAs) are known to be major posttranscriptional regulators that can enhance or repress translation by binding to the 5= untranslated region (UTR) of mRNA targets with the help of a chaperone protein, Hfq. In this study, we investigated the expression of acrA, acrB, and tolC translational fusions using 27 Hfq-dependent sRNAs overexpressed from plasmids. No significant sRNA regulation of acrA or acrB was detected. SdsR (also known as RyeB), an abundant and well-conserved stationary-phase sRNA, was found to repress the expression of tolC, the gene encoding the outer membrane protein of many multidrug resistance efflux pumps. This repression was shown to be by direct base pairing occurring upstream from the ribosomal binding site. SdsR overexpression and its regulation of tolC were found to reduce resistance to novobiocin and crystal violet. Our results suggest that additional targets for SdsR exist that contribute to increased antibiotic sensitivity and reduced biofilm formation. In an effort to identify phenotypes associated with single-copy SdsR and its regulation of tolC, the effect of a deletion of sdsR or mutations in tolC that should block SdsR pairing were investigated using a Biolog phenotypic microarray. However, no significant phenotypes were identified. Therefore, SdsR appears to modulate rather than act as a major regulator of its targets. IMPORTANCEAcrAB-TolC is a major efflux pump present in E. coli and Gram-negative bacteria used to export toxic compounds; the pump confers resistance to many antibiotics of unrelated classes. In this study, we found that SdsR, a small RNA expressed in stationary phase, repressed the expression of tolC, resulting in increased sensitivity to some antibiotics. This extends the findings of previous studies showing that sRNAs contribute to the regulation of many outer membrane proteins; manipulating or enhancing their action might help in sensitizing bacteria to antibiotics.

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Section: Discussionsupporting

confidence: 82%

Small RNA Regulation of TolC, the Outer Membrane Component of Bacterial Multidrug Transporters

Parker

Gottesman

2016

J Bacteriol

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“…Some studies have shown that the novel protein aatA, which is encoded on EAEC virulence plasmid pAA2, localizes to the outer membrane of this bacterium and facilitates export of the dispersin aap across the outer membrane. 45,46 Our results may support this notion because aatA and aap were detected in greater than 68% of patients with diarrhea. Further study is required for a firm conclusion.…”

supporting

confidence: 80%

Pediatric Diarrhea in Southern Ghana: Etiology and Association with Intestinal Inflammation and Malnutrition

Opintan¹,

Newman²,

Ayeh‐Kumi³

et al. 2010

The American Society of Tropical Medicine and Hygiene

103

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Abstract. Diarrhea is a major public health problem that affects the development of children. Anthropometric data were collected from 274 children with ( N = 170) and without ( N = 104) diarrhea. Stool specimens were analyzed by conventional culture, polymerase chain reaction for enteroaggregative Escherichia coli (EAEC), Shigella , Cryptosporidium , Entamoeba , and Giardia species, and by enzyme-linked immunosorbent assay for fecal lactoferrin levels. About 50% of the study population was mildly to severely malnourished. Fecal lactoferrin levels were higher in children with diarrhea ( P = 0.019). Children who had EAEC infection, with or without diarrhea, had high mean lactoferrin levels regardless of nutritional status. The EAEC and Cryptosporidium were associated with diarrhea ( P = 0.048 and 0.011, respectively), and malnourished children who had diarrhea were often co-infected with both Cryptosporidium and EAEC. In conclusion, the use of DNA-biomarkers revealed that EAEC and Cryptosporidium were common intestinal pathogens in Accra, and that elevated lactoferrin was associated with diarrhea in this group of children.

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“…PA␤N in combination with an iron chelator showed synergistic activity against P. aeruginosa biofilm development (890). Similar to the role of TolC, a plasmid encoding a TolC homolog, AatA, promoted aggregation and biofilm formation of an enteroaggregative E. coli isolate (891). A large conjugative plasmid encoding the OqxAB pump and type 3 fimbriae enabled E. coli to form a biofilm (892).…”

Section: Role Of Efflux Pumps In Biofilm Formation and Resistancementioning

confidence: 98%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

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SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

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The Escherichia coli Efflux Pump TolC Promotes Aggregation of Enteroaggregative E. coli 042

Cited by 36 publications

References 46 publications

Small RNA Regulation of TolC, the Outer Membrane Component of Bacterial Multidrug Transporters

Small RNA Regulation of TolC, the Outer Membrane Component of Bacterial Multidrug Transporters

Pediatric Diarrhea in Southern Ghana: Etiology and Association with Intestinal Inflammation and Malnutrition

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

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