scholarly journals Nicotinic Acid Modulates Legionella pneumophila Gene Expression and Induces Virulence Traits

2013 ◽  
Vol 81 (3) ◽  
pp. 945-955 ◽  
Author(s):  
Rachel L. Edwards ◽  
Andrew Bryan ◽  
Matthieu Jules ◽  
Kaoru Harada ◽  
Carmen Buchrieser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nicotinic Acid ◽  
Cell Fate ◽  
Legionella Pneumophila ◽  
Acid Treatment ◽  
Fatty Acid Biosynthesis ◽  
Profile Analysis ◽  
Major Facilitator Superfamily ◽  
Content Type ◽  
Major Facilitator

ABSTRACTIn response to environmental fluctuations or stresses, bacteria can activate transcriptional and phenotypic programs to coordinate an adaptive response. The intracellular pathogenLegionella pneumophilaconverts from a noninfectious replicative form to an infectious transmissive form when the bacterium encounters alterations in either amino acid concentrations or fatty acid biosynthesis. Here, we report thatL. pneumophiladifferentiation is also triggered by nicotinic acid, a precursor of the central metabolite NAD+. In particular, when replicativeL. pneumophilaare treated with 5 mM nicotinic acid, the bacteria induce numerous transmissive-phase phenotypes, including motility, cytotoxicity toward macrophages, sodium sensitivity, and lysosome avoidance. Transcriptional profile analysis determined that nicotinic acid induces the expression of a panel of genes characteristic of transmissive-phaseL. pneumophila. Moreover, an additional 213 genes specific to nicotinic acid treatment were altered. Although nearly 25% of these genes lack an assigned function, the gene most highly induced by nicotinic acid treatment encodes a putative major facilitator superfamily transporter, Lpg0273. Indeed,lpg0273protectsL. pneumophilafrom toxic concentrations of nicotinic acid as judged by analyzing the growth of the corresponding mutant. The broad utility of the nicotinic acid pathway to couple central metabolism and cell fate is underscored by this small metabolite's modulation of gene expression by diverse microbes, includingCandida glabrata,Bordetella pertussis,Escherichia coli, andL. pneumophila.

scholarly journals ThephtC-phtDLocus Equips Legionella pneumophila for Thymidine Salvage and Replication in Macrophages

2013 ◽  
Vol 82 (2) ◽  
pp. 720-730 ◽  
Author(s):  
Maris V. Fonseca ◽  
John-Demian Sauer ◽  
Sebastien Crepin ◽  
Brenda Byrne ◽  
Michele S. Swanson
Keyword(s):  
Escherichia Coli ◽  
Life Cycle ◽  
Thymidylate Synthase ◽  
Legionella Pneumophila ◽  
Opportunistic Pathogen ◽  
Nucleoside Transporters ◽  
Major Facilitator Superfamily ◽  
Pyrimidine Nucleoside ◽  
Content Type ◽  
Major Facilitator

ABSTRACTThe phagosomal transporter (Pht) family of the major facilitator superfamily (MFS) is encoded by phylogenetically related intracellular gammaproteobacteria, including the opportunistic pathogenLegionella pneumophila. The location of thephtgenes between the putative thymidine kinase (tdk) and phosphopentomutase (deoB) genes suggested that thephtCandphtDloci contribute to thymidine salvage inL. pneumophila. Indeed, aphtC+allele intransrestored pyrimidine uptake to anEscherichia colimutant that lacked all known nucleoside transporters, whereas aphtD+allele did not. The results of phenotypic analyses ofL. pneumophilastrains lackingphtCorphtDstrongly indicate thatL. pneumophilarequires PhtC and PhtD function under conditions where sustained dTMP synthesis is compromised. First, in broth cultures that mimicked thymidine limitation or starvation,L. pneumophilaexhibited a marked requirement for PhtC function. Conversely, mutation ofphtDconferred a survival advantage. Second, in medium that lacked thymidine, multicopyphtC+orphtD+alleles enhanced the survival ofL. pneumophilathymidylate synthase (thyA)-deficient strains, which cannot synthesize dTMP endogenously. Third, under conditions in which transport of the pyrimidine nucleoside analog 5-fluorodeoxyuridine (FUdR) would inhibit growth, PhtC and PhtD conferred a growth advantage toL. pneumophilathyA+strains. Finally, when cultured in macrophages,L. pneumophilarequired thephtC-phtDlocus to replicate. Accordingly, we propose that PhtC and PhtD contribute to protectL. pneumophilafrom dTMP starvation during its intracellular life cycle.

scholarly journals Widespread effects of nicotinic acid on gene expression in insulin-sensitive tissues: implications for unwanted effects of nicotinic acid treatment

Metabolism ◽  
2011 ◽  
Vol 60 (1) ◽  
pp. 134-144 ◽  
Author(s):  
Sangdun Choi ◽  
Hana Yoon ◽  
Ki-Sook Oh ◽  
Young Taek Oh ◽  
Young I. Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nicotinic Acid ◽  
Acid Treatment

scholarly journals The major facilitator superfamily-type protein LbtC promotes the utilization of the legiobactin siderophore by Legionella pneumophila

Microbiology ◽  
2012 ◽  
Vol 158 (3) ◽  
pp. 721-735 ◽  
Author(s):  
Christa H. Chatfield ◽  
Brendan J. Mulhern ◽  
V. K. Viswanathan ◽  
Nicholas P. Cianciotto
Keyword(s):  
Legionella Pneumophila ◽  
Major Facilitator Superfamily ◽  
Type Protein ◽  
Major Facilitator

scholarly journals iac Gene Expression in the Indole-3-Acetic Acid-Degrading Soil Bacterium Enterobacter soli LF7

2018 ◽  
Vol 84 (19) ◽  
Author(s):  
Isaac V. Greenhut ◽  
Beryl L. Slezak ◽  
Johan H. J. Leveau
Keyword(s):  
Gene Expression ◽  
Acetic Acid ◽  
Promoter Region ◽  
Deletion Mutant ◽  
Plant Hormone ◽  
Major Facilitator Superfamily ◽  
Soil Bacterium ◽  
Content Type ◽  
Indole 3 Acetic Acid

ABSTRACT We show for soil bacterium Enterobacter soli LF7 that the possession of an indole-3-acetic acid catabolic (iac) gene cluster is causatively linked to the ability to utilize the plant hormone indole-3-acetic acid (IAA) as a carbon and energy source. Genome-wide transcriptional profiling by mRNA sequencing revealed that these iac genes, chromosomally arranged as iacHABICDEFG and coding for the transformation of IAA to catechol, were the most highly induced (>29-fold) among the relatively few (<1%) differentially expressed genes in response to IAA. Also highly induced and immediately downstream of the iac cluster were genes for a major facilitator superfamily protein (mfs) and enzymes of the β-ketoadipate pathway (pcaIJD-catBCA), which channels catechol into central metabolism. This entire iacHABICDEFG-mfs-pcaIJD-catBCA gene set was constitutively expressed in an iacR deletion mutant, confirming the role of iacR, annotated as coding for a MarR-type regulator and located upstream of iacH, as a repressor of iac gene expression. In E. soli LF7 carrying the DNA region upstream of iacH fused to a promoterless gfp gene, green fluorescence accumulated in response to IAA at concentrations as low as 1.6 μM. The iacH promoter region also responded to chlorinated IAA, but not other aromatics tested, indicating a narrow substrate specificity. In an iacR deletion mutant, gfp expression from the iacH promoter region was constitutive, consistent with the predicted role of iacR as a repressor. A deletion analysis revealed putative −35/−10 promoter sequences upstream of iacH, as well as a possible binding site for the IacR repressor. IMPORTANCE Bacterial iac genes code for the enzymatic conversion of the plant hormone indole-3-acetic acid (IAA) to catechol. Here, we demonstrate that the iac genes of soil bacterium Enterobacter soli LF7 enable growth on IAA by coarrangement and coexpression with a set of pca and cat genes that code for complete conversion of catechol to central metabolites. This work contributes in a number of novel and significant ways to our understanding of iac gene biology in bacteria from (non-)plant environments. More specifically, we show that LF7's response to IAA involves derepression of the MarR-type transcriptional regulator IacR, which is quite fast (less than 25 min upon IAA exposure), highly specific (only in response to IAA and chlorinated IAA, and with few genes other than iac, cat, and pca induced), relatively sensitive (low micromolar range), and seemingly tailored to exploit IAA as a source of carbon and energy.

scholarly journals Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Sean D. Liston ◽  
Luke Whitesell ◽  
Mili Kapoor ◽  
Karen Joy Shaw ◽  
Leah E. Cowen
Keyword(s):  
Fungal Pathogens ◽  
Candida Parapsilosis ◽  
Efflux Pump ◽  
Major Facilitator Superfamily ◽  
Transporter Gene ◽  
Transcription Factor Gene ◽  
Content Type ◽  
Atp Binding Cassette Transporter ◽  
Major Facilitator Superfamily Transporter ◽  
Major Facilitator

ABSTRACT Manogepix is a broad-spectrum antifungal agent that inhibits glycosylphosphatidylinositol (GPI) anchor biosynthesis. Using whole-genome sequencing, we characterized two efflux-mediated mechanisms in the fungal pathogens Candida albicans and Candida parapsilosis that resulted in decreased manogepix susceptibility. In C. albicans, a gain-of-function mutation in the transcription factor gene ZCF29 activated expression of ATP-binding cassette transporter genes CDR11 and SNQ2. In C. parapsilosis, a mitochondrial deletion activated expression of the major facilitator superfamily transporter gene MDR1.

scholarly journals ThemelREDCAOperon Encodes a Utilization System for the Raffinose Family of Oligosaccharides inBacillus subtilis

2019 ◽  
Vol 201 (15) ◽  
Author(s):  
Kambiz Morabbi Heravi ◽  
Hildegard Watzlawick ◽  
Josef Altenbuchner
Keyword(s):  
Bacillus Subtilis ◽  
Transcriptional Start Site ◽  
Major Facilitator Superfamily ◽  
Atp Binding ◽  
Carbohydrate Utilization ◽  
Content Type ◽  
Storage Organs ◽  
Major Facilitator ◽  
Atp Binding Cassette

ABSTRACTBacillus subtilisis a heterotrophic soil bacterium that hydrolyzes different polysaccharides mainly found in the decomposed plants. These carbohydrates are mainly cellulose, hemicellulose, and the raffinose family of oligosaccharides (RFOs). RFOs are soluble α-galactosides, such as raffinose, stachyose, and verbascose, that rank second only after sucrose in abundance. Genome sequencing and transcriptome analysis ofB. subtilisindicated the presence of a putative α-galactosidase-encoding gene (melA) located in themsmRE-amyDC-melAoperon. Characterization of the MelA protein showed that it is a strictly Mn2+- and NAD+-dependent α-galactosidase able to hydrolyze melibiose, raffinose, and stachyose. Transcription of themsmER-amyDC-melAoperon is under control of a σA-type promoter located upstream ofmsmR(PmsmR), which is negatively regulated by MsmR. The activity of PmsmRwas induced in the presence of melibiose and raffinose. MsmR is a transcriptional repressor that binds to two binding sites at PmsmRlocated upstream of the −35 box and downstream of the transcriptional start site. MsmEX-AmyCD forms an ATP-binding cassette (ABC) transporter that probably transports melibiose into the cell. SincemsmRE-amyDC-melAis a melibiose utilization system, we renamed the operonmelREDCA.IMPORTANCEBacillus subtilisutilizes different polysaccharides produced by plants. These carbohydrates are primarily degraded by extracellular hydrolases, and the resulting oligo-, di-, and monosaccharides are transported into the cytosol via phosphoenolpyruvate-dependent phosphotransferase systems (PTS), major facilitator superfamily, and ATP-binding cassette (ABC) transporters. In this study, a new carbohydrate utilization system ofB. subtilisresponsible for the utilization of α-galactosides of the raffinose family of oligosaccharides (RFOs) was investigated. RFOs are synthesized from sucrose in plants and are mainly found in the storage organs of plant leaves. Our results revealed the modus operandi of a new carbohydrate utilization system inB. subtilis.

scholarly journals γ-Resorcylate Catabolic-Pathway Genes in the Soil Actinomycete Rhodococcus jostii RHA1

2015 ◽  
Vol 81 (21) ◽  
pp. 7656-7665 ◽  
Author(s):  
Daisuke Kasai ◽  
Naoto Araki ◽  
Kota Motoi ◽  
Shota Yoshikawa ◽  
Toju Iino ◽  
...  
Keyword(s):  
Major Facilitator Superfamily ◽  
Pcr Analysis ◽  
Decarboxylase Activity ◽  
Content Type ◽  
Reverse Transcription Pcr ◽  
Intergenic Regions ◽  
Major Facilitator Superfamily Transporter ◽  
Maleylacetate Reductase ◽  
Major Facilitator ◽  
Rhodococcus Jostii

ABSTRACTTheRhodococcus jostiiRHA1 gene cluster required for γ-resorcylate (GRA) catabolism was characterized. The cluster includestsdA,tsdB,tsdC,tsdD,tsdR,tsdT, andtsdX, which encode GRA decarboxylase, resorcinol 4-hydroxylase, hydroxyquinol 1,2-dioxygenase, maleylacetate reductase, an IclR-type regulator, a major facilitator superfamily transporter, and a putative hydrolase, respectively. ThetsdAgene conferred GRA decarboxylase activity onEscherichia coli. Purified TsdB oxidized NADH in the presence of resorcinol, suggesting thattsdBencodes a unique NADH-specific single-component resorcinol 4-hydroxylase. Mutations in eithertsdAortsdBresulted in growth deficiency on GRA. ThetsdCandtsdDgenes conferred hydroxyquinol 1,2-dioxygenase and maleylacetate reductase activities, respectively, onE. coli. Inactivation oftsdTsignificantly retarded the growth of RHA1 on GRA. The growth retardation was partially suppressed under acidic conditions, suggesting the involvement oftsdTin GRA uptake. Reverse transcription-PCR analysis revealed that thetsdgenes constitute three transcriptional units, thetsdBADCandtsdTXoperons andtsdR. Transcription of thetsdBADCandtsdTXoperons was induced during growth on GRA. Inactivation oftsdRderepressed transcription of thetsdBADCandtsdTXoperons in the absence of GRA, suggesting thattsdgene transcription is negatively regulated by thetsdR-encoded regulator. Binding of TsdR to thetsdR-tsdBandtsdT-tsdRintergenic regions was inhibited by the addition of GRA, indicating that GRA interacts with TsdR as an effector molecule.

scholarly journals IcgA Is a Virulence Factor of Rhodococcus equi That Modulates Intracellular Growth

2014 ◽  
Vol 82 (5) ◽  
pp. 1793-1800 ◽  
Author(s):  
Xiaoguang Wang ◽  
Garry B. Coulson ◽  
Aleksandra A. Miranda-CasoLuengo ◽  
Raúl Miranda-CasoLuengo ◽  
Mary K. Hondalus ◽  
...  
Keyword(s):  
Virulence Factor ◽  
Pathogenicity Island ◽  
Rhodococcus Equi ◽  
Transport Protein ◽  
Major Facilitator Superfamily ◽  
Conjugative Plasmid ◽  
Intracellular Growth ◽  
Content Type ◽  
Growth Phenotype ◽  
Major Facilitator

ABSTRACTVirulence of the intracellular pathogenRhodococcus equidepends on a 21.3-kb pathogenicity island located on a conjugative plasmid. To date, the only nonregulatory pathogenicity island-encoded virulence factor identified is the cell envelope-associated VapA protein. Although the pathogenicity islands from porcine and equineR. equiisolates have undergone major rearrangements, thevirRoperon (virR-icgA-vapH-orf7-virS) is highly conserved in both, suggesting these genes play an important role in pathogenicity. VirR and VirS are transcriptional regulators controlling expression of pathogenicity island genes, includingvapA. Here, we show that whilevapHandorf7are dispensable for intracellular growth ofR. equi, deletion oficgA, formerly known asorf5, encoding a major facilitator superfamily transport protein, elicited an enhanced growth phenotype in macrophages and a significant reduction in macrophage viability, while extracellular growth in broth remained unaffected. Transcription ofvirS, located downstream oficgA, andvapAwas not affected by theicgAdeletion during growth in broth or in macrophages, showing that the enhanced growth phenotype caused by deletion oficgAwas not mediated through abnormal transcription of these genes. Transcription oficgAincreased 6-fold within 2 h following infection of macrophages and remained significantly higher 48 h postinfection compared to levels at the start of the infection. The major facilitator superfamily transport protein IcgA is the first factor identified inR. equithat negatively affects intracellular replication. Aside from VapA, it is only the second pathogenicity island-encoded structural protein shown to play a direct role in intracellular growth of this pathogenic actinomycete.

scholarly journals Discovering Novel Bile Protection Systems in Bifidobacterium breve UCC2003 through Functional Genomics

2011 ◽  
Vol 78 (4) ◽  
pp. 1123-1131 ◽  
Author(s):  
Lorena Ruiz ◽  
Aldert Zomer ◽  
Mary O'Connell-Motherway ◽  
Douwe van Sinderen ◽  
Abelardo Margolles
Keyword(s):  
Major Facilitator Superfamily ◽  
Transport Systems ◽  
Content Type ◽  
Bifidobacterium Breve ◽  
Enhanced Resistance ◽  
Protection Systems ◽  
Genes Encoding ◽  
Major Facilitator ◽  
Inducible Genes ◽  
Selection Of

ABSTRACTTolerance of gut commensals to bile salt exposure is an important feature for their survival in and colonization of the intestinal environment. A transcriptomic approach was employed to study the response ofBifidobacterium breveUCC2003 to bile, allowing the identification of a number of bile-induced genes with a range of predicted functions. The potential roles of a selection of these bile-inducible genes in bile protection were analyzed following heterologous expression inLactococcus lactis. Genes encoding three transport systems belonging to the major facilitator superfamily (MFS), Bbr_0838, Bbr_0832, and Bbr_1756, and three ABC-type transporters, Bbr_0406-0407, Bbr_1804-1805, and Bbr_1826-1827, were thus investigated and shown to provide enhanced resistance and survival to bile exposure. This work significantly improves our understanding as to how bifidobacteria respond to and survive bile exposure.

scholarly journals AbuO, a TolC-Like Outer Membrane Protein of Acinetobacter baumannii, Is Involved in Antimicrobial and Oxidative Stress Resistance

2014 ◽  
Vol 59 (2) ◽  
pp. 1236-1245 ◽  
Author(s):  
Vijaya Bharathi Srinivasan ◽  
Vasanth Vaidyanathan ◽  
Govindan Rajamohan
Keyword(s):  
Oxidative Stress ◽  
Acinetobacter Baumannii ◽  
Outer Membrane ◽  
Efflux Pump ◽  
Outer Membrane Proteins ◽  
Major Facilitator Superfamily ◽  
Pcr Analysis ◽  
Content Type ◽  
Major Facilitator ◽  
And Oxidative Stress

ABSTRACTAlthoughAcinetobacter baumanniiis well accepted as a nosocomial pathogen, only a few of the outer membrane proteins (OMPs) have been functionally characterized. In this study, we demonstrate the biological functions of AbuO, a homolog of TolC fromEscherichia coli. Inactivation ofabuOled to increased sensitivity to high osmolarity and oxidative stress challenge. The ΔabuOmutant displayed increased susceptibility to antibiotics, such as amikacin, carbenicillin, ceftriaxone, meropenem, streptomycin, and tigecycline, and hospital-based disinfectants, such as benzalkonium chloride and chlorhexidine. The reverse transcription (RT)-PCR analysis indicated increased expression of efflux pumps (resistance nodulation cell division [RND] efflux pumpacrD, 8-fold; SMR-typeemrEhomolog, 12-fold; and major facilitator superfamily [MFS]-typeampGhomolog, 2.7-fold) and two-component response regulators (baeR, 4.67-fold;ompR, 10.43-fold) in the ΔabuOmutant together with downregulation ofrstA(4.22-fold) and the pilin chaperone (9-fold). The isogenic mutant displayed lower virulence in a nematode model (P< 0.01). Experimental evidence for the binding of MerR-type transcriptional regulator SoxR to radiolabeledabuOpromoter suggests regulation ofabuOby SoxR inA. baumannii.

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