Deletion of the Correia element in the mtr gene complex of Neisseria meningitidis

Enriquez, Rocío; Abad, Raquel; Chanto, Grettel; Corso, Alejandra; Cruces, Raquel; Gabastou, Jean Marc; Gorla, Maria Cecília Outeiro; Maldonado, Aurora; Moreno, Jaime; Rouzic, Erwan Muros‐Le; Sorhouet, Cecilia; Vázquez, Julio

doi:10.1099/jmm.0.021220-0

Cited by 7 publications

(5 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This will be a useful resource for future investigations. For example, a recent survey reported that meningococcal strains deleted for the CE upstream of mtrCDE did not have a reduced level of drug resistance [41]. This would have been anticipated by our result, which shows that the α-right Y128C repeat (the relevant Correia end in this example) has low promoter activity (Table 2)…”

Section: Resultssupporting

confidence: 76%

The Transposon-Like Correia Elements Encode Numerous Strong Promoters and Provide a Potential New Mechanism for Phase Variation in the Meningococcus

2011

View full text Add to dashboard Cite

Neisseria meningitidis is the primary causative agent of bacterial meningitis. The genome is rich in repetitive DNA and almost 2% is occupied by a diminutive transposon called the Correia element. Here we report a bioinformatic analysis defining eight subtypes of the element with four distinct types of ends. Transcriptional analysis, using PCR and a lacZ reporter system, revealed that two ends in particular encode strong promoters. The activity of the strongest promoter is dictated by a recurrent polymorphism (Y128) at the right end of the element. We highlight examples of elements that appear to drive transcription of adjacent genes and others that may express small non-coding RNAs. Pair-wise comparisons between three meningococcal genomes revealed that no more than two-thirds of Correia elements maintain their subtype at any particular locus. This is due to recombinational class switching between elements in a single strain. Upon switching subtype, a new allele is available to spread through the population by natural transformation. This process may represent a hitherto unrecognized mechanism for phase variation in the meningococcus. We conclude that the strain-to-strain variability of the Correia elements, and the large number of strong promoters encoded by them, allows for potentially widespread effects within the population as a whole. By defining the strength of the promoters encoded by the eight subtypes of Correia ends, we provide a resource that allows the transcriptional effects of a particular subtype at a given locus to be predicted.

show abstract

Section: Resultssupporting

confidence: 76%

The Transposon-Like Correia Elements Encode Numerous Strong Promoters and Provide a Potential New Mechanism for Phase Variation in the Meningococcus

2011

View full text Add to dashboard Cite

show abstract

“…With the expression of nadA varying significantly between MC strains [13], [14], mutations affecting farR and/or mtrR expression may have more profound effects on nadA expression than those observed here. Deletion of the Correia element or IHF binding site upstream from mtrR affects expression of mtrCDE , which is an MtrR target [32]; Enriquez et al observed several MC isolates with Correia element deletions upstream from mtrR , including one serotype B, suggesting that these mutations are not an exception [34]. We propose that this multi-layered regulation of nadA , which now includes direct regulation by MtrR, reflects an effort by MC to balance levels of the NadA adhesion important for interacting with host cells yet avoiding potentially protective antibody responses.…”

Section: Resultsmentioning

confidence: 99%

MtrR Control of a Transcriptional Regulatory Pathway in Neisseria meningitidis That Influences Expression of a Gene (nadA) Encoding a Vaccine Candidate

Cloward

Shafer

2013

PLoS ONE

View full text Add to dashboard Cite

The surface-exposed NadA adhesin produced by a subset of capsular serogroup B strains of Neisseria meningitidis is currently being considered as a vaccine candidate to prevent invasive disease caused by a hypervirulent lineage of meningococci. Levels of NadA are known to be controlled by both transcriptional regulatory factors and a component of human saliva, 4-hydroxyphenylacetic acid. Herein, we confirmed the capacity of a DNA-binding protein termed FarR to negatively control nadA expression. We also found that a known transcriptional regulator of farR in N. gonorrhoeae termed MtrR can have a negative regulatory impact on farR and nadA expression, especially when over-expressed. MtrR-mediated repression of nadA was found to be direct, and its binding to a target DNA sequence containing the nadA promoter influenced formation and/or stability of FarR::nadA complexes. The complexity of the multi-layered regulation of nadA uncovered during this investigation suggests that N. meningitidis modulates NadA adhesin protein levels for the purpose of interacting with host cells yet avoiding antibody directed against surface exposed epitopes.

show abstract

“…(commonly 153 to 157 bp or 104 to 108 bp) with an inverted repeat and a characteristic core (such as the integration host factor) that are involved in gene regulation (872). Intriguingly, CREE deletions do not show an effect on susceptibility to ciprofloxacin, erythromycin, and rifampin (873). However, whether these deletions could affect mtrCDE expression remains unknown.…”

Section: Neisseria Efflux Pumpsmentioning

confidence: 99%

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

2015

View full text Add to dashboard Cite

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.

show abstract

Deletion of the Correia element in the mtr gene complex of Neisseria meningitidis

Cited by 7 publications

References 12 publications

The Transposon-Like Correia Elements Encode Numerous Strong Promoters and Provide a Potential New Mechanism for Phase Variation in the Meningococcus

The Transposon-Like Correia Elements Encode Numerous Strong Promoters and Provide a Potential New Mechanism for Phase Variation in the Meningococcus

MtrR Control of a Transcriptional Regulatory Pathway in Neisseria meningitidis That Influences Expression of a Gene (nadA) Encoding a Vaccine Candidate

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

Contact Info

Product

Resources

About