Deregulation of the Arginine Deiminase (arc) Operon in Penicillin-Tolerant Mutants ofStreptococcus gordonii

ABSTRACT Penicillin tolerance is an incompletely understood phenomenon that allows bacteria to resist drug-induced killing. Tolerance was studied with independent Streptococcus gordonii mutants generated by cyclic exposure to 500 times the MIC of penicillin. Parent cultures lost 4 to 5 log10 CFU/ml of viable counts/24 h. In contrast, each of four independent mutant cultures lost ≤2 log10 CFU/ml/24 h. The mutants had unchanged penicillin-binding proteins but contained increased amounts of two proteins with respective masses of ca. 50 and 45 kDa. One mutant (Tol1) was further characterized. The two proteins showing increased levels were homologous to the arginine deiminase and ornithine carbamoyl transferase of other gram-positive bacteria and were encoded by an operon that was >80% similar to the arginine-deiminase (arc) operon of these organisms. Partial nucleotide sequencing and insertion inactivation of the S. gordonii arc locus indicated that tolerance was not a direct consequence of arc alteration. On the other hand, genetic transformation of tolerance by Tol1 DNA always conferredarc deregulation. In nontolerant recipients,arc was repressed during exponential growth and up-regulated during postexponential growth. In tolerant transformants,arc was constitutively expressed. Tol1 DNA transformed tolerance at the same rate as transformation of a point mutation (10−2 to 10−3). The tolerance mutation mapped on a specific chromosomal fragment but was physically distant fromarc. Importantly, arc deregulation was observed in most (6 of 10) of additional independent penicillin-tolerant mutants. Thus, although not exclusive, the association betweenarc deregulation and tolerance was not fortuitous. Since penicillin selection mimicked the antibiotic pressure operating in the clinical environment, arc deregulation might be an important correlate of naturally occurring tolerance and help in understanding the mechanism(s) underlying this clinically problematic phenotype.

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Curcumin-mediated photodynamic antimicrobial chemotherapy (PACT): a systematic review / Quimioterapia fotodinâmica antimicrobiana (PACT) mediada por curcumina: uma revisão sistemática

Brazilian Journal of Health Review ◽

10.34119/bjhrv4n6-201 ◽

2021 ◽

Vol 4 (6) ◽

pp. 26142-26152

Author(s):

Eduardo Cândido da Silva ◽

Ulrich Vasconcelos

Keyword(s):

Systematic Review ◽

Antimicrobial Chemotherapy ◽

Light Emitting Diode ◽

Antibiofilm Activity ◽

Short Wavelength Range ◽

Light Emitting ◽

Gram Positive Bacteria ◽

Photodynamic Antimicrobial Chemotherapy ◽

Naturally Occurring ◽

Aims And Scope

Light energy is known to be used to combat microbial growth. Photodynamic antimicrobial chemotherapy (PACT) has the potential to use different naturally-occurring compounds, such as photosensitizers. Curcumin is an example of a molecule of interest in different areas under different optics. This systematic review surveys the aims and scope of research on curcumin-mediated PACT published between January 2011 and December 2020. The search was carried out in MEDLINE, PubMed, EMBASE and Periódicos CAPES databases employing the keywords “Photodynamic antimicrobial chemotherapy”, “photosensitizer”, “curcumin” and the descriptor “Light-Emitting Diode”. It was observed that in the last decade little material meeting these criteria was published. Brazilian institutions concentrated most of their studies on cytotoxic activity. The most recent work, however, focused on antibiofilm activity. Gram-positive bacteria are more sensitive to curcumin-mediated PACT over a short wavelength range. Different concentrations and exposure time of the photosensitizer were evaluated, but the amount of information is still insufficient to establish the best treatment condition as the number of tested pathogens is still poor.

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Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb/β3 integrin

Blood ◽

10.1182/blood-2012-01-406322 ◽

2012 ◽

Vol 119 (26) ◽

pp. 6317-6325 ◽

Cited By ~ 27

Author(s):

Daniel W. Bougie ◽

Mark Rasmussen ◽

Jieqing Zhu ◽

Richard H. Aster

Keyword(s):

Binding Sites ◽

Structural Changes ◽

Recognition Site ◽

Platelet Inhibitors ◽

Head Region ◽

Drug Induced ◽

Naturally Occurring ◽

Β3 Integrin ◽

Effect Of Treatment ◽

Arginine Glycine Aspartic Acid

Arginine-glycine-aspartic acid (RGD)–mimetic platelet inhibitors act by occupying the RGD recognition site of αIIb/β3 integrin (GPIIb/IIIa), thereby preventing the activated integrin from reacting with fibrinogen. Thrombocytopenia is a well-known side effect of treatment with this class of drugs and is caused by Abs, often naturally occurring, that recognize αIIb/β3 in a complex with the drug being administered. RGD peptide and RGD-mimetic drugs are known to induce epitopes (ligand-induced binding sites [LIBS]) in αIIb/β3 that are recognized by certain mAbs. It has been speculated, but not shown experimentally, that Abs from patients who develop thrombocytopenia when treated with an RGD-mimetic inhibitor similarly recognize LIBS determinants. We addressed this question by comparing the reactions of patient Abs and LIBS-specific mAbs against αIIb/β3 in a complex with RGD and RGD-mimetic drugs, and by examining the ability of selected non-LIBS mAbs to block binding of patient Abs to the liganded integrin. Findings made provide evidence that the patient Abs recognize subtle, drug-induced structural changes in the integrin head region that are clustered about the RGD recognition site. The target epitopes differ from classic LIBS determinants, however, both in their location and by virtue of being largely drug-specific.

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Relationship Between Crystal Structure, Internal Stress and Properties in the Naturally Occurring Supportless Thin Films of Chrysotile Asbestos

MRS Proceedings ◽

10.1557/proc-356-105 ◽

1994 ◽

Vol 356 ◽

Author(s):

Georges Denes ◽

R. Le Van Mao ◽

A. Vaillancourt

Keyword(s):

Direct Consequence ◽

Structural Formula ◽

Thin Layers ◽

Magnesium Ions ◽

Chrysotile Asbestos ◽

X Ray Diffraction ◽

X Ray ◽

Naturally Occurring ◽

Enormous Amount ◽

Unit Cells

AbstractChrysotile asbestos (empirical formula: Mg3Si2O7.2H2O, structural formula: Mg3Si2O5(OH)4) crystallizes in a sheet structure so thin that it is equivalent to a thin film that has no support. The magnesium ions are too large to fit comfortably in their octahedral sites, the size of which is determined by the network of SiO4 tetrahedra. The squeezing of the magnesium ions in sites that are too tight forces the thin layers to bend and coil around themselves. The bending of the unit-cells results in the presence of an enormous amount of highly directional stress, which has been analyzed by X-ray diffraction. The carcinogenic properties of chrysotile asbestos are a direct consequence of this stress.

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Structure, Regulation, and Putative Function of the Arginine Deiminase System of Streptococcus suis

Journal of Bacteriology ◽

10.1128/jb.188.2.361-369.2006 ◽

2006 ◽

Vol 188 (2) ◽

pp. 361-369 ◽

Cited By ~ 85

Author(s):

Petra Gruening ◽

Marcus Fulde ◽

Peter Valentin-Weigand ◽

Ralph Goethe

Keyword(s):

Binding Site ◽

Streptococcus Suis ◽

Arginine Deiminase ◽

Knockout Mutant ◽

Transcription Regulator ◽

Protective Antigens ◽

Ornithine Carbamoyl Transferase ◽

Young Pigs ◽

Arginine Repressor ◽

Carbamate Kinase

ABSTRACT Streptococcus suis is an important cause of infectious diseases in young pigs. Little is known about the virulence factors or protective antigens of S. suis. Recently, we have identified two proteins of the arginine deiminase system (ADS) of S. suis, which were temperature induced and expressed on the streptococcal surface (N. Winterhoff, R. Goethe, P. Gruening, M. Rohde, H. Kalisz, H. E. Smith, and P. Valentin-Weigand, J. Bacteriol. 184:6768-6776, 2002). In the present study, we analyzed the complete ADS of S. suis. Due to their homologies to the recently published S. gordonii ADS genes, the genes for arginine deiminase, ornithine carbamoyl-transferase, and carbamate kinase, which were previously designated adiS, octS, and ckS, respectively, were renamed arcA, arcB, and arcC, respectively. Our data revealed that arcA, arcB, and arcC of the S. suis ADS are transcribed from an operon (arcABC operon). Additionally, putative ADS-associated genes were cloned and sequenced which, however, did not belong to the arcABC operon. These were the flpS gene upstream of the arcABC operon with homology to the flp transcription regulator of S. gordonii and the arcD, arcT, arcH, and argR genes downstream of the arcABC operon with high homologies to a putative arginine-ornithine antiporter, a putative dipeptidase of S. gordonii, a putative β-N-acetylhexosaminidase of S. pneumoniae, and a putative arginine repressor of S. gordonii, respectively. The transcriptional start point of the arcABC operon was determined, and promoter analysis provided evidence that multiple factors contribute to the regulation of the ADS. Thus, a putative binding site for a transcription regulator of the Crp/Fnr family, an ArgR-binding site, and two cis-acting catabolite response elements were identified in the promoter-operator region of the operon. Consistent with this, we could demonstrate that the ADS of S. suis is inducible by arginine and reduced O2 tension and subject to carbon catabolite repression. Furthermore, comparing an arcA knockout mutant in which expression of the three operon-encoded proteins was abolished with the parental wild-type strain showed that the arcABC operon of S. suis contributes to survival under acidic conditions.

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Katanosin B and Plusbacin A3, Inhibitors of Peptidoglycan Synthesis in Methicillin-ResistantStaphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.6.1823-1827.2001 ◽

2001 ◽

Vol 45 (6) ◽

pp. 1823-1827 ◽

Cited By ~ 63

Author(s):

Hideki Maki ◽

Kenji Miura ◽

Yoshinori Yamano

Keyword(s):

Cell Wall ◽

Antibacterial Activity ◽

Whole Cells ◽

Gram Positive Bacteria ◽

Peptidoglycan Synthesis ◽

Cyclic Depsipeptide ◽

Naturally Occurring ◽

Vancomycin Resistant Enterococci ◽

Vancomycin Resistant

ABSTRACT Both katanosin B and plusbacin A3 are naturally occurring cyclic depsipeptide antibiotics containing a lactone linkage. They showed strong antibacterial activity against methicillin-resistantStaphylococcus aureus and VanA-type vancomycin-resistant enterococci, with MICs ranging from 0.39 to 3.13 μg/ml, as well as against other gram-positive bacteria. They inhibited the incorporation of N-acetylglucosamine, a precursor of cell wall synthesis, into peptidoglycan of S. aureus whole cells at concentrations close to their MICs. In vitro studies with a wall-membrane particulate fraction of S. aureus showed that katanosin B and plusbacin A3 inhibited the formation of lipid intermediates, with 50% inhibitory concentrations (IC50s) of 2.2 and 2.3 μg/ml, respectively, and inhibited the formation of nascent peptidoglycan, with IC50s of 0.8 and 0.4 μg/ml, respectively. Vancomycin, a well-known inhibitor of transglycosylation, did not inhibit the formation of lipid intermediates but did inhibit the formation of nascent peptidoglycan, with an IC50 of 4.1 μg/ml. Acetyl-Lys-d-Ala-d-Ala, an analog of the terminus of the lipid intermediates, effectively suppressed the inhibition of transglycosylation by vancomycin, but did not suppress those by katanosin B and plusbacin A3. These results indicate that the antibacterial activity of katanosin B and plusbacin A3 is due to blocking of transglycosylation and its foregoing steps of cell wall peptidoglycan synthesis via a mechanism differing from that of vancomycin.

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THE α-GLYCEROPHOSPHATE IN DROSOPHILA MELANOGASTER II. GENETIC ASPECTS

Genetics ◽

10.1093/genetics/71.1.127 ◽

1972 ◽

Vol 71 (1) ◽

pp. 127-138

Author(s):

Stephen J O'Brien ◽

Ross J Macintyre

Keyword(s):

Drosophila Melanogaster ◽

Energy Production ◽

Null Alleles ◽

Electrophoretic Variant ◽

Electrophoretic Variants ◽

Glycerophosphate Dehydrogenase ◽

Naturally Occurring ◽

Relative Viability ◽

Null Mutants ◽

Independent Mutant

ABSTRACT Seven alleles of the α-Glycerophosphate dehydrogenase-1 (αGpdh-1) locus of Drosophila melanogaster have been described. These include two naturally occurring electrophoretic variants, one EMS-induced electrophoretic variant, and four EMS-induced "null" or "zero" mutants. With the electrophoretic variants, the locus was mapped to II-20.5 ± 2.5. A complementation matrix was prepared utilizing the null mutants. Three of the four mutants and a deletion of the locus (Grell 1967) exhibit dosage dependency. The dosage independent mutant exhibits complementation with two of the other null alleles. Flies genetically deficient in α-glycerophosphate dehydrogenase are fertile, but their relative viability is severely diminished. Such flies also lose the ability to sustain flight, an observation consistent with the enzyme's function in energy production. The levels of mitochondrial α-glycerophosphate oxidase, measured in flies genetically deficient in the cytoplasmic enzyme, were normal.

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An Unusual Case of Drug-Induced Thrombocytopenia

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709620947891 ◽

2020 ◽

Vol 8 ◽

pp. 232470962094789

Author(s):

Shiyu Wang ◽

Khalid Sawalha ◽

Atif Khan

Keyword(s):

Conformational Changes ◽

Rapid Onset ◽

Drug Eluting Stent ◽

Inpatient Setting ◽

Drug Induced ◽

Platelet Surface ◽

Naturally Occurring ◽

Antiplatelet Medication ◽

Platelet Receptor ◽

Obtuse Marginal

Drug-induced thrombocytopenia (DIT) is a differential diagnosis for consideration when acute thrombocytopenia is encountered in the outpatient or inpatient setting. The mechanism of thrombocytopenia induced by different antiplatelet therapies varies. DIT may occur due to antibody formation following the exposure to a drug, or naturally occurring preexisting antibodies may produce rapid-onset thrombocytopenia when a drug molecule binds to a platelet receptor inducing a conformational change thus rendering it to be an antigen target for naturally occurring antibodies. A 66-year-old female with history of hypertension presented with non-ST elevation myocardial infarction, had drug eluting stent placed in first obtuse marginal artery of left circumflex coronary artery. Started on antiplatelet medications aspirin 81 mg, ticagrelor 90 mg (which was later transitioned to clopidogrel 75 mg), as well as tirofiban 12.5 mg (for 12 hours only). Tirofiban is a GP IIb/IIIa antagonist, other drugs in this class have been documented to induce thrombocytopenia as well, but rates for tirofiban appear to be the highest, the reason is unclear. These antibodies are thought to be either naturally occurring or induced from conformational changes to GP IIb/IIIa binding site after binding to the GP IIb/IIIa receptor, binding of these drugs to the receptor precipitates an epitope much more specific for platelet surface antigens. Tirofiban and clopidogrel/ticagrelor can cause thrombocytopenia, but onset in this case is unusual: acute antibody reaction would be expected within hours, not delayed 30 hours after starting antiplatelet medication, and nonacute reaction would present 1 to 2 weeks out.

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Antimicrobial characterization and safety aspects of the bacteriocinogenicEnterococcus hiraeF420 isolated from Moroccan raw goat milk

Canadian Journal of Microbiology ◽

10.1139/w2012-027 ◽

2012 ◽

Vol 58 (5) ◽

pp. 596-604 ◽

Cited By ~ 4

Author(s):

F. Achemchem ◽

R. Cebrián ◽

J. Abrini ◽

M. Martínez-Bueno ◽

E. Valdivia ◽

...

Keyword(s):

Structural Gene ◽

Food Systems ◽

Goat Milk ◽

Mass Spectrometry Analysis ◽

Decarboxylase Activity ◽

Strong Activity ◽

Spectrometry Analysis ◽

Gram Positive Bacteria ◽

Naturally Occurring ◽

Resistance To Heat

The F420 strain, isolated from raw goat milk and identified as Enterococcus hirae , was selected because of its strong activity against Gram-positive bacteria, including Listeria monocytogenes . Interestingly, the F420 strain lacks the virulence genes and decarboxylase activity of histidine, lysine, and ornithine, and it is susceptible to 11 of 14 tested antibiotics, including vancomycin. The antimicrobial compounds produced by E. hirae F420 strain showed high resistance to heat treatment and to acidic and basic pHs. The MALDI-TOF mass spectrometry analysis coupled with the sequence of peptide and structural gene analysis of one of the purified enterocins showed 100% identity with enterocin P (EntP), previously described in E. faecium strains. The structural gene for EntP is located on a plasmid of 65 kb. Other enterocins with molecular mass higher than 7 kDa were also detected. This is the first report of the production of EntP by E. hirae species naturally occurring in foods. The biotechnological characteristics of the F420 strain and its enterocins indicate their potential for application in the control of L. monocytogenes and other undesirable bacteria in food systems.

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Clonal relationships among naturally occurring nicotinamide-requiringSalmonella typhimurium

Genetics Research ◽

10.1017/s0016672300022746 ◽

1985 ◽

Vol 46 (3) ◽

pp. 241-250 ◽

Cited By ~ 1

Author(s):

Ruth M. Barker ◽

A. A. Yousuf

Keyword(s):

Salmonella Typhimurium ◽

Phage Type ◽

Mutant Line ◽

Phage Types ◽

Sequence Of Events ◽

Naturally Occurring ◽

Independent Mutant

SUMMARYSalmonella typhimuriumstrains of biotype 25x have been shown in transductional cross experiments to be clonal in the Nad character. The ancestral bacterium, probably of biotype 25a, mutated to a requirement for nicotinamide and subsequently diversified in phage type and secondary biotype characters. Such a sequence of events indicates interconversion among phage types 6, 16, 46, 49, 73, 76 and 135. Strains in biotypes 1x, 9ix, 17x, 17dx, 19dx and 25hix yielded Nad+recombinants in interbiotype crosses, suggesting that each originated as an independent mutant line.

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Extremely tough cyclic peptide nanopolymers

MRS Advances ◽

10.1557/adv.2019.363 ◽

2019 ◽

Vol 4 (46-47) ◽

pp. 2527-2532 ◽

Cited By ~ 1

Author(s):

Manoj K. Kolel-Veetil ◽

LCDR Luis Estrella ◽

Christopher R. So ◽

Kenan P. Fears

Keyword(s):

Self Assembly ◽

Cyclic Peptides ◽

Cyclic Peptide ◽

Molecular Architecture ◽

Gram Negative ◽

Gram Positive Bacteria ◽

New Class ◽

Ca 50 ◽

Bioinspired Nanomaterials ◽

Linear Polymer Chain

ABSTRACTWe present a new class of bioinspired nanomaterials that are stabilized by a combination of covalent and hydrogen bonds. Prior work by others has shown that cyclic peptides can self-assemble to form supramolecular assemblies through backbone-backbone hydrogen bonding. To improve upon this molecular architecture, we develop a synthesis route to polymerize cyclic peptides and form a linear polymer chain that can transition between a rigid nanorod and an unfolded conformation. For a cyclic peptide polymer containing amine-terminated side chains on each ring, we demonstrate self-assembly can be triggered in aqueous solutions by varying the pH. We measure the elastic modulus of the rigid nanorods to be ca. 50 GPa, which is comparable to our molecular dynamics (MD) prediction (ca. 64 GPa). Our results highlight the uniqueness of our molecular architecture, namely their exemplary toughness (up to 3 GJ m-3), in comparison to other cyclic peptide-based assemblies. Finally, we demonstrate amphiphilic cyclic β-peptides are capable of inhibiting the growth of gram-negative and gram-positive bacteria.

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