Bacterial DNA topology and infectious disease

Dorman, Charles J.; Corcoran, Colin P.

doi:10.1093/nar/gkn996

Cited by 64 publications

(46 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, evidence to support this hypothesis is currently lacking. Expression of genes associated with bacterial virulence, such as invasion and flagellar genes, is influenced by changes in DNA supercoiling (13) and is activated by quorum sensing (10,41). As efflux pumps have been shown to expel quorum-sensing signals (7,33), it is reasonable to speculate that altered quorum-sensing signal homeostasis, resulting from increased AcrAB activity and/or altered DNA supercoiling, may have contributed to the decreased virulence of isolates in this study.…”

Section: Vol 54 2010 Fluoroquinolone Resistance and Fitness Costs 371mentioning

confidence: 81%

Fitness Costs and Stability of a High-Level Ciprofloxacin Resistance Phenotype in Salmonella enterica Serotype Enteritidis: Reduced Infectivity Associated with Decreased Expression of Salmonella Pathogenicity Island 1 Genes

O'Regan

Quinn

Frye

et al. 2010

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The fitness costs associated with high-level fluoroquinolone resistance were examined for phenotypically and genotypically characterized ciprofloxacin-resistant Salmonella enterica serotype Enteritidis mutants (104-cip and 5408-cip; MIC, >32 g/ml). The stability of the fluoroquinolone resistance phenotype in both mutants was investigated to assess whether clones with better fitness could emerge in the absence of antibiotic selective pressure. Mutants 104-cip and 5408-cip displayed altered morphology on agar and by electron microscopy, reduced growth rates, motility and invasiveness in Caco-2 cells, and increased sensitivity to environmental stresses. Microarray data revealed decreased expression of virulence and motility genes in both mutants. Two clones, 104-revert and 1A-revertC2, with ciprofloxacin MICs of 3 and 2 g/ml, respectively, were recovered from separate lineages of 104-cip after 20 and 70 passages, respectively, on antibiotic-free agar. All fitness costs, except motility, were reversed in 104-revert. Potential mechanisms associated with reversal of the resistance phenotype were examined. Compared to 104-cip, both 104-revert and 1A-revertC2 showed decreased expression of acrB and soxS but still overexpressed marA. Both acquired additional mutations in SoxR and ParC, and 1A-revertC2 acquired two mutations in MarA. The altered porin and lipopolysaccharide (LPS) profiles observed in 104-cip were reversed. In contrast, 5408-cip showed no reversal in fitness costs and maintained its high-level ciprofloxacin resistance for 200 passages on antibiotic-free agar. In conclusion, high-level ciprofloxacin resistance in S. Enteritidis is associated with fitness costs. In the absence of antibiotic selection pressure, isolates may acquire mutations enabling reversion to an intermediate-level ciprofloxacin resistance phenotype associated with less significant fitness costs.

show abstract

Section: Vol 54 2010 Fluoroquinolone Resistance and Fitness Costs 371mentioning

confidence: 81%

Fitness Costs and Stability of a High-Level Ciprofloxacin Resistance Phenotype in Salmonella enterica Serotype Enteritidis: Reduced Infectivity Associated with Decreased Expression of Salmonella Pathogenicity Island 1 Genes

O'Regan

Quinn

Frye

et al. 2010

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…6A). Since such stretches of DNA could be potential targets for regulatory proteins (41,56) or alter the DNA structure with distant effects of promoter activity through local changes in DNA topology (12,13), we wondered whether the 53-bp highly AT-rich region would impinge on the activity or osmotic control of the yqiHIK promoter. To assess a possible function of the ATrich region, we constructed a set of deletions with endpoints located either at the borderline of the AT-rich region (⌬1) or at two positions within the AT-rich region (⌬2 and ⌬3) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Activity of the Osmotically Regulated yqiHIK Promoter from Bacillus subtilis Is Controlled at a Distance

Fischer

Bremer

2012

J Bacteriol

View full text Add to dashboard Cite

The yqiHIK gene cluster from Bacillus subtilis is predicted to encode an extracellular lipoprotein (YqiH), a secreted N-acetylmuramoyl-L-alanine amidase (YqiI), and a cytoplasmic glycerophosphodiester phosphodiesterase (YqiK). Reverse transcriptase PCR (RT-PCR) analysis showed that the yqiHIK genes are transcribed as an operon. Consistent with the in silico prediction, we found that the purified YqiI protein exhibited hydrolytic activity toward peptidoglycan sacculi. Transcription studies with yqiHtreA reporter fusion strains revealed that the expression of yqiHIK is subjected to finely tuned osmotic control, but enhanced expression occurs only in severely osmotically stressed cells. Primer extension analysis pinpointed the osmotically responsive yqiHIK promoter, and site-directed mutagenesis was employed to assess functionally important sequences required for promoter activity and osmotic control. Promoter variants with constitutive activity were isolated. A deletion analysis of the yqiHIK regulatory region showed that a 53-bp AT-rich DNA segment positioned 180 bp upstream of the ؊35 sequence is critical for the activity and osmotic regulation of the yqiHIK promoter. Hence, the expression of yqiHIK is subjected to genetic control at a distance. Upon the onset of growth of cells of the B. subtilis wild-type strain in high-salinity medium (1.2 M NaCl), we observed gross morphological deformations of cells that were then reversed to a rod-shaped morphology again when the cells had adjusted to the high-salinity environment. The products of the yqiHIK gene cluster were not critical for reestablishing rod-shaped morphology, but the deletion of this operon yielded a B. subtilis mutant impaired in growth in a defined minimal medium and at high salinity.

show abstract

“…In addition, DNA topology plays a more general role in the expression of virulence genes in pathogenic bacteria at different phases of the host-pathogen relationship. In fact, supercoiling levels control the gene regulatory network of the cell hierarchically, influencing the activities of a large number of promoters simultaneously [187].…”

Section: Discussionmentioning

confidence: 99%

In front of and behind the replication fork: bacterial type IIA topoisomerases

Sissi

Palumbo

2010

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Topoisomerases are vital enzymes specialized in controlling DNA topology, in particular supercoiling and decatenation, to properly handle nucleic acid packing and cell dynamics. The type IIA enzymes act by cleaving both strands of a double helix and having another strand from the same or another molecule cross the DNA gate before a re-sealing event completes the catalytic cycle. Here, we will consider the two types of IIA prokaryotic topoisomerases, DNA Gyrase and Topoisomerase IV, as crucial regulators of bacterial cell cycle progression. Their synergistic action allows control of chromosome packing and grants occurrence of functional transcription and replication processes. In addition to displaying a fascinating molecular mechanism of action, which transduces chemical energy into mechanical energy by means of large conformational changes, these enzymes represent attractive pharmacological targets for antibacterial chemotherapy.

show abstract

Bacterial DNA topology and infectious disease

Cited by 64 publications

References 71 publications

Fitness Costs and Stability of a High-Level Ciprofloxacin Resistance Phenotype in Salmonella enterica Serotype Enteritidis: Reduced Infectivity Associated with Decreased Expression of Salmonella Pathogenicity Island 1 Genes

Fitness Costs and Stability of a High-Level Ciprofloxacin Resistance Phenotype in Salmonella enterica Serotype Enteritidis: Reduced Infectivity Associated with Decreased Expression of Salmonella Pathogenicity Island 1 Genes

Activity of the Osmotically Regulated yqiHIK Promoter from Bacillus subtilis Is Controlled at a Distance

In front of and behind the replication fork: bacterial type IIA topoisomerases

Contact Info

Product

Resources

About