scholarly journals The Global Regulatory Cyclic AMP Receptor Protein (CRP) Controls Multifactorial Fluoroquinolone Susceptibility in Salmonella enterica Serovar Typhimurium

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Stefani C. Kary ◽  
Joshua R. K. Yoneda ◽  
Stephen C. Olshefsky ◽  
Laura A. Stewart ◽  
Steven B. West ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Salmonella Enterica ◽  
Topoisomerase I ◽  
Multiple Drug Resistance ◽  
Regulatory Protein ◽  
Dna Supercoiling ◽  
Receptor Protein ◽  
Multiple Drug ◽  
Topoisomerase Iv ◽  
Fluoroquinolone Antibiotics

ABSTRACT Fluoroquinolone antibiotics are prescribed for the treatment of Salmonella enterica infections, but resistance to this family of antibiotics is growing. Here we report that loss of the global regulatory protein cyclic AMP (cAMP) receptor protein (CRP) or its allosteric effector, cAMP, reduces susceptibility to fluoroquinolones. A Δcrp mutation was synergistic with the primary fluoroquinolone resistance allele gyrA83, thus able to contribute to clinically relevant resistance. Decreased susceptibility to fluoroquinolones could be partly explained by decreased expression of the outer membrane porin genes ompA and ompF with a concomitant increase in the expression of the ciprofloxacin resistance efflux pump gene acrB in Δcrp cells. Expression of gyrAB, which encode the DNA supercoiling enzyme GyrAB, which is blocked by fluoroquinolones, and expression of topA, which encodes the dominant supercoiling-relaxing enzyme topoisomerase I, were unchanged in Δcrp cells. Yet Δcrp cells maintained a more relaxed state of DNA supercoiling, correlating with an observed increase in topoisomerase IV (parCE) expression. Surprisingly, the Δcrp mutation had the unanticipated effect of enhancing fitness in the presence of fluoroquinolone antibiotics, which can be explained by the observation that exposure of Δcrp cells to ciprofloxacin had the counterintuitive effect of restoring wild-type levels of DNA supercoiling. Consistent with this, Δcrp cells did not become elongated or induce the SOS response when challenged with ciprofloxacin. These findings implicate the combined action of multiple drug resistance mechanisms in Δcrp cells: reduced permeability and elevated efflux of fluoroquinolones coupled with a relaxed DNA supercoiling state that buffers cells against GyrAB inhibition by fluoroquinolones.

scholarly journals Developmental-stage-specific expression and regulation of an amphotropic retroviral receptor in hematopoietic cells.

1996 ◽  
Vol 16 (8) ◽  
pp. 4240-4247 ◽  
Author(s):  
C Richardson ◽  
A Bank
Keyword(s):  
Gene Transfer ◽  
Multiple Drug Resistance ◽  
Fetal Liver ◽  
Phosphate Transport ◽  
Receptor Protein ◽  
Multiple Drug ◽  
Free Medium ◽  
Specific Expression ◽  
Retroviral Transduction

Expression of the transmembrane receptor protein Ram-1 may be critical to optimizing retroviral gene transfer. Ram-1 acts as both a sodium-dependent phosphate transporter and a receptor for amphotropic retroviruses. We previously reported detectable Ram-1 in murine hematopoietic fetal liver cells (FLC) despite resistance of these cells to amphotropic retroviral transduction (infection). We document here that Ram-1 expression is completely absent in murine yolk sac cells from days 9.5 through 13.5 of ontogeny and first appears at low levels in midgestational FLC between days 13.5 and 14.5. In addition, Ram-1 expression is detected only in more differentiated populations within FLC, day 14.5, and not in those highly enriched for stem cells, indicating developmental regulation of Ram-1 during murine hematopoiesis. Others have reported the in vitro use of phosphate-free medium as a stimulus to increase levels of Ram-1 mRNA in nonhematopoietic cells. We now demonstrate that Ram-1 poly(A)+ mRNA increases significantly following culture of FLC in phosphate-free medium. Further, transduction of FLC in phosphate-free medium with an amphotropic retrovirus containing the multiple drug resistance gene leads to gene transfer not observed previously. These data demonstrate that (i) the normal resistance of FLC to amphotropic transduction is most likely due to an insufficient number of Ram-1 molecules for efficient retroviral recognition and binding, and (ii) Ram-1 can be upregulated by increasing the need for phosphate transport across the cell membrane.

scholarly journals Molecular Cloning and Characterization of the Salmonella enterica Serovar Paratyphi B rma Gene, Which Confers Multiple Drug Resistance in Escherichia coli

2002 ◽  
Vol 46 (2) ◽  
pp. 360-366 ◽  
Author(s):  
Mahmoud. A. Yassien ◽  
Hosam E. Ewis ◽  
Chung-Dar Lu ◽  
Ahmed T. Abdelal
Keyword(s):  
Escherichia Coli ◽  
Drug Resistance ◽  
Salmonella Enterica ◽  
Genomic Library ◽  
Multiple Drug Resistance ◽  
Protein Profile ◽  
Multiple Drug ◽  
E Coli ◽  
Paratyphi B ◽  
High Degree

ABSTRACT A genomic library from a strain of Salmonella enterica serovar Paratyphi B that exhibits multiple drug resistance (MDR) was constructed in Escherichia coli. Two of the recombinant plasmids, pNOR5 and pNOR5, conferred resistance only to fluoroquinolones in E. coli, whereas the third, pNCTR4, conferred the MDR phenotype. Sequence and subcloning analysis showed that it is the presence of RecA on the first two plasmids which confers resistance to fluoroquinolones in E. coli. A similar analysis established that the MDR phenotype conferred by pNCTR4 is due to a gene, rma (resistance to multiple antibiotics), which encodes a 13.5-kDa polypeptide. The derived sequence for Rma exhibits a high degree of similarity to those of a group of MarA-like activators that confer MDR in E. coli. A MalE-Rma fusion protein was purified to near homogeneity and was shown to interact with a DNA fragment carrying a MarA operator sequence. Furthermore, overexpression of rma in E. coli caused changes in the outer membrane protein profile that were similar to those reported for MarA. These results suggest that Rma might act as a transcriptional activator of the marA regulon.

scholarly journals International lineages of Salmonella enterica serovars isolated from chicken farms, Wakiso District, Uganda

2019 ◽  
Author(s):  
Takiyah A. Ball ◽  
Daniel F. Monte ◽  
Awa Aidara-Kane ◽  
Jorge Matheu ◽  
Hongyu Ru ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Surveillance System ◽  
Multiple Drug Resistance ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Seasonal Difference ◽  
Health Concern ◽  
Multiple Drug ◽  
Public Health Concern ◽  
Cattle Farms

ABSTRACTThe growing occurrence of multidrug-resistant (MDR) Salmonella enterica in poultry has been reported with public health concern worldwide. We reported, recently, the occurrence of Escherichia coli and Salmonella enterica serovars carrying clinically relevant resistance genes in dairy cattle farms in the Wakiso District, Uganda, highlighting an urgent need to monitor food-producing animal environments. Here, we present the prevalence, antimicrobial resistance, and sequence type of 51 Salmonella isolates recovered from 400 environmental samples from chicken farms in Uganda. Among the Salmonella isolates, 32/51 (62.7%) were resistant to at least one antimicrobial, and 10/51 (19.6%) displayed multiple drug resistance. Through PCR, five replicon plasmids were identified among all chicken Salmonella including IncFIIS 17/51 (33.3%), IncI1α 12/51 (23.5%), IncP 8/51 (15.7%), IncX1 8/51 (15.7%), and IncX2 1/51 (2.0%). In addition, we identified replicons through WGS (ColpVC and IncFIB). A significant seasonal difference between chicken sampling periods was observed (p= 0.0017). We conclude that MDR Salmonella highlights the risks posed to the animals, environment, and humans for infection. Implementing a robust integrated surveillance system in Uganda will help monitor MDR to help control infectious threats.

scholarly journals Multiple-Drug Resistance in d-Tartrate-Positive Salmonella enterica Serovar Paratyphi B Isolates from Poultry Is Mediated by Class 2 Integrons Inserted into the Bacterial Chromosome

2003 ◽  
Vol 47 (11) ◽  
pp. 3640-3643 ◽  
Author(s):  
Angelika Miko ◽  
Karin Pries ◽  
Andreas Schroeter ◽  
Reiner Helmuth
Keyword(s):  
Drug Resistance ◽  
Salmonella Enterica ◽  
Multiple Drug Resistance ◽  
Bacterial Chromosome ◽  
Multiple Drug ◽  
Class 1 Integron ◽  
Gene Cassettes ◽  
Class 1 ◽  
Paratyphi B

ABSTRACT The presence of integrons in 85 multiresistant German isolates of the predominating Salmonella enterica subsp. enterica serovar Paratyphi B dT+ clone was investigated. All isolates possessed a chromosomally located Tn7-like class 2 integron carrying the same dfrA1-sat1-aadA1 array of gene cassettes. Only four isolates (4.7%) revealed an additional class 1 integron with two strains each containing the aadA1 or dfrA1-aadA1 gene cassettes.

Topoisomerase I in multiple drug resistance

1993 ◽  
Vol 12 (1-3) ◽  
pp. 127-135 ◽  
Author(s):  
Augusto Pessina
Keyword(s):  
Drug Resistance ◽  
Topoisomerase I ◽  
Multiple Drug Resistance ◽  
Multiple Drug

scholarly journals Catabolite Repression of the Propionate Catabolic Genes in Escherichia coli and Salmonella enterica: Evidence for Involvement of the Cyclic AMP Receptor Protein

2005 ◽  
Vol 187 (8) ◽  
pp. 2793-2800 ◽  
Author(s):  
Sung Kuk Lee ◽  
Jack D. Newman ◽  
Jay D. Keasling
Keyword(s):  
Escherichia Coli ◽  
Cyclic Amp ◽  
Transcriptional Activation ◽  
Salmonella Enterica ◽  
Catabolite Repression ◽  
Targeted Mutagenesis ◽  
Receptor Protein ◽  
Sigma 54 ◽  
Catabolic Genes ◽  
Serovar Typhimurium

ABSTRACT Previous studies with Salmonella enterica serovar Typhimurium LT2 demonstrated that transcriptional activation of the prpBCDE operon requires the function of transcription factor PrpR, sigma-54, and IHF. In this study, we found that transcription from the prpBCDE and prpR promoters was down-regulated by the addition of glucose or glycerol, indicating that these genes may be regulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex. Targeted mutagenesis of a putative CRP-binding site in the promoter region between prpR and prpBCDE suggested that these genes are under the control of CRP. Furthermore, cells with defects in cya or crp exhibited reduced transcriptional activation of prpR and prpBCDE in Escherichia coli. These results demonstrate that propionate metabolism is subject to catabolite repression by the global transcriptional regulator CRP and that this regulation is effected through control of both the regulator gene prpR and the prpBCDE operon itself. The unique properties of the regulation of these two divergent promoters may have important implications for mechanisms of CRP-dependent catabolite repression acting in conjunction with a member of the sigma-54 family of transcriptional activators.

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