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Full-Text Articles in Medicine and Health Sciences
Prevalence Of Streptococci And Increased Polymicrobial Diversity Associated With Cystic Fibrosis Patient Stability, L. M. Filkins, T. H. Hampton, A. H. Gifford, M. J. Gross, D. A. Hogan, M. L. Sogin, H. G. Morrison, B. J. Paster, G. A. O'Toole
Prevalence Of Streptococci And Increased Polymicrobial Diversity Associated With Cystic Fibrosis Patient Stability, L. M. Filkins, T. H. Hampton, A. H. Gifford, M. J. Gross, D. A. Hogan, M. L. Sogin, H. G. Morrison, B. J. Paster, G. A. O'Toole
Dartmouth Scholarship
Diverse microbial communities chronically colonize the lungs of cystic fibrosis patients. Pyrosequencing of amplicons for hypervariable regions in the 16S rRNA gene generated taxonomic profiles of bacterial communities for sputum genomic DNA samples from 22 patients during a state of clinical stability (outpatients) and 13 patients during acute exacerbation (inpatients). We employed quantitative PCR (qPCR) to confirm the detection of Pseudomonas aeruginosa and Streptococcus by the pyrosequencing data and human oral microbe identification microarray (HOMIM) analysis to determine the species of the streptococci identified by pyrosequencing. We show that outpatient sputum samples have significantly higher bacterial diversity than inpatients, but …
Whole-Genome Sequencing Of Staphylococcus Aureus Strain Rn4220, A Key Laboratory Strain Used In Virulence Research, Identifies Mutations That Affect Not Only Virulence Factors But Also The Fitness Of The Strain, Dhanalakshmi Nair, Guido Memmi, David Hernandez, Jonathan Bard, Marie Beaume, Steven Gill, Patrice Francois, Ambrose L. Cheung
Whole-Genome Sequencing Of Staphylococcus Aureus Strain Rn4220, A Key Laboratory Strain Used In Virulence Research, Identifies Mutations That Affect Not Only Virulence Factors But Also The Fitness Of The Strain, Dhanalakshmi Nair, Guido Memmi, David Hernandez, Jonathan Bard, Marie Beaume, Steven Gill, Patrice Francois, Ambrose L. Cheung
Dartmouth Scholarship
Staphylococcus aureus RN4220, a cloning intermediate, is sometimes used in virulence, resistance, and metabolic studies. Using whole-genome sequencing, we showed that RN4220 differs from NCTC8325 and contains a number of genetic polymorphisms that affect both virulence and general fitness, implying a need for caution in using this strain for such studies.
Salicylic Acid Diminishes Staphylococcus Aureus Capsular Polysaccharide Type 5 Expression, Lucia P. Alvarez, Maria S. Barbagelata, Mariana Gordiola, A. L. Cheung
Salicylic Acid Diminishes Staphylococcus Aureus Capsular Polysaccharide Type 5 Expression, Lucia P. Alvarez, Maria S. Barbagelata, Mariana Gordiola, A. L. Cheung
Dartmouth Scholarship
Capsular polysaccharides (CP) of serotypes 5 (CP5) and 8 (CP8) are major Staphylococcus aureus virulence factors. Previous studies have shown that salicylic acid (SAL), the main aspirin metabolite, affects the expression of certain bacterial virulence factors. In the present study, we found that S. aureus strain Reynolds (CP5) cultured with SAL was internalized by MAC-T cells in larger numbers than strain Reynolds organisms not exposed to SAL. Furthermore, the internalization of the isogenic nonencapsulated Reynolds strain into MAC-T cells was not significantly affected by preexposure to SAL. Pretreatment of S. aureus strain Newman with SAL also enhanced internalization into MAC-T …
Role Of Pknb Kinase In Antibiotic Resistance And Virulence In Community-Acquired Methicillin-Resistant Staphylococcus Aureus Strain Usa300, S. Tamber, J. Schwartzman, A. L. Cheung
Role Of Pknb Kinase In Antibiotic Resistance And Virulence In Community-Acquired Methicillin-Resistant Staphylococcus Aureus Strain Usa300, S. Tamber, J. Schwartzman, A. L. Cheung
Dartmouth Scholarship
The regulation of cellular processes by eukaryote-like serine/threonine kinases is widespread in bacteria. In the last 2 years, several studies have examined the role of serine/threonine kinases in Staphylococcus aureus on cell wall metabolism, autolysis, and virulence, mostly in S. aureus laboratory isolates in the 8325-4 lineage. In this study, we showed that the pknB gene (also called stk1) of methicillin-resistant S. aureus (MRSA) strain COL and the community-acquired MRSA (CA-MRSA) strain USA300 is involved in cell wall metabolism, with the pknB mutant exhibiting enhanced sensitivity to β-lactam antibiotics but not to other classes of antibiotics, including aminoglycosides, ciprofloxacin, …
Proteolytic Regulation Of Toxin-Antitoxin Systems By Clppc In Staphylococcus Aureus, Niles P. Donegan, Earl T. Thompson, Zhibiao Fu, Ambrose L. Cheung
Proteolytic Regulation Of Toxin-Antitoxin Systems By Clppc In Staphylococcus Aureus, Niles P. Donegan, Earl T. Thompson, Zhibiao Fu, Ambrose L. Cheung
Dartmouth Scholarship
Bacterial toxin-antitoxin (TA) systems typically consist of a small, labile antitoxin that inactivates a specific longer-lived toxin. In Escherichia coli, such antitoxins are proteolytically regulated by the ATP-dependent proteases Lon and ClpP. Under normal conditions, antitoxin synthesis is sufficient to replace this loss from proteolysis, and the bacterium remains protected from the toxin. However, if TA production is interrupted, antitoxin levels decrease, and the cognate toxin is free to inhibit the specific cellular component, such as mRNA, DnaB, or gyrase. To date, antitoxin degradation has been studied only in E. coli, so it remains unclear whether similar mechanisms of regulation …
Genetic Evidence For An Alternative Citrate-Dependent Biofilm Formation Pathway In Staphylococcus Aureus That Is Dependent On Fibronectin Binding Proteins And The Grars Two-Component Regulatory System, Robert M. Q. Shanks, Michael A. Meehl, Kimberly M. Brothers, Raquel M. Martinez, Niles P. Donegan, Martha L. Graber, Ambrose L. Cheung, George A. O'Toole
Genetic Evidence For An Alternative Citrate-Dependent Biofilm Formation Pathway In Staphylococcus Aureus That Is Dependent On Fibronectin Binding Proteins And The Grars Two-Component Regulatory System, Robert M. Q. Shanks, Michael A. Meehl, Kimberly M. Brothers, Raquel M. Martinez, Niles P. Donegan, Martha L. Graber, Ambrose L. Cheung, George A. O'Toole
Dartmouth Scholarship
We reported previously that low concentrations of sodium citrate strongly promote biofilm formation by Staphylococcus aureus laboratory strains and clinical isolates. Here, we show that citrate promotes biofilm formation via stimulating both cell-to-surface and cell-to-cell interactions. Citrate-stimulated biofilm formation is independent of the ica locus, and in fact, citrate represses polysaccharide adhesin production. We show that fibronectin binding proteins FnbA and FnbB and the global regulator SarA, which positively regulates fnbA and fnbB gene expression, are required for citrate's positive effects on biofilm formation, and citrate also stimulates fnbA and fnbB gene expression. Biofilm formation is also stimulated by several …
Staphylococcus Aureus Escapes More Efficiently From The Phagosome Of A Cystic Fibrosis Bronchial Epithelial Cell Line Than From Its Normal Counterpart, Todd M. Jarry, Ambrose L. Cheung
Staphylococcus Aureus Escapes More Efficiently From The Phagosome Of A Cystic Fibrosis Bronchial Epithelial Cell Line Than From Its Normal Counterpart, Todd M. Jarry, Ambrose L. Cheung
Dartmouth Scholarship
Staphylococcus aureus is frequently the initial bacterium isolated from young cystic fibrosis (CF) patients, and yet its role in CF disease progression has not been determined. Recent data from our lab demonstrates that S. aureus can invade and replicate within the CF tracheal epithelial cell line (CFT-1). Here we describe the finding that the fate of internalized S. aureus in CFT-1 cells differs from its complemented counterpart (LCFSN). S. aureus strain RN6390 was able to replicate within the mutant CFT-1 cells after invasion but not in the complemented LCFSN cells. At 1 h postinvasion, S. aureus containing vesicles within both …
Transposon Disruption Of The Complex I Nadh Oxidoreductase Gene (Snod) In Staphylococcus Aureus Is Associated With Reduced Susceptibility To The Microbicidal Activity Of Thrombin-Induced Platelet Microbicidal Protein 1, Arnold S. Bayer, Peter Mcnamara, Michael R. Yeaman, Natalie Lucindo, Tiffanny Jones, Ambrose L. Cheung
Transposon Disruption Of The Complex I Nadh Oxidoreductase Gene (Snod) In Staphylococcus Aureus Is Associated With Reduced Susceptibility To The Microbicidal Activity Of Thrombin-Induced Platelet Microbicidal Protein 1, Arnold S. Bayer, Peter Mcnamara, Michael R. Yeaman, Natalie Lucindo, Tiffanny Jones, Ambrose L. Cheung
Dartmouth Scholarship
The cationic molecule thrombin-induced platelet microbicidal protein 1 (tPMP-1) exerts potent activity against Staphylococcus aureus. We previously reported that a Tn551 S. aureus transposon mutant, ISP479R, and two bacteriophage back-transductants, TxA and TxB, exhibit reduced in vitro susceptibility to tPMP-1 (tPMP-1(r)) compared to the parental strain, ISP479C (V. Dhawan, M. R. Yeaman, A. L. Cheung, E. Kim, P. M. Sullam, and A. S. Bayer, Infect. Immun. 65:3293-3299, 1997). In the current study, the genetic basis for tPMP-1(r) in these mutants was identified. GenBank homology searches using sequence corresponding to chromosomal DNA flanking Tn551 mutant strains showed that the fourth gene …
Heparin Stimulates Staphylococcus Aureus Biofilm Formation, Robert M. Q. Shanks, Niles P. Donegan, Martha L. Graber, Sarah E. Buckingham, Michael Zegans, Ambrose Cheung, George A. O'Toole
Heparin Stimulates Staphylococcus Aureus Biofilm Formation, Robert M. Q. Shanks, Niles P. Donegan, Martha L. Graber, Sarah E. Buckingham, Michael Zegans, Ambrose Cheung, George A. O'Toole
Dartmouth Scholarship
Heparin, known for its anticoagulant activity, is commonly used in catheter locks. Staphylococcus aureus, a versatile human and animal pathogen, is commonly associated with catheter-related bloodstream infections and has evolved a number of mechanisms through which it adheres to biotic and abiotic surfaces. We demonstrate that heparin increased biofilm formation by several S. aureus strains. Surface coverage and the kinetics of biofilm formation were stimulated, but primary attachment to the surface was not affected. Heparin increased S. aureus cell-cell interactions in a protein synthesis-dependent manner. The addition of heparin rescued biofilm formation of hla, ica, and sarA …
Role Of The Distal Sara Promoters In Sara Expression In Staphylococcus Aureus, Ambrose L. Cheung, Adhar C. Manna
Role Of The Distal Sara Promoters In Sara Expression In Staphylococcus Aureus, Ambrose L. Cheung, Adhar C. Manna
Dartmouth Scholarship
The global regulatory locus sarA comprises a 375-bp open reading frame that is driven by three promoters, the proximal P1 and distal P3 and P2 promoters. We mutated the weaker P3 and P2 promoters to ascertain the effect of the change on SarA protein and target gene expression. Our results indicated that the solely active P1 promoter led to a lower SarA protein level, which has an effect on agr transcription and subsequently had corresponding effects on hla, sspA, and spa transcription, probably in both agr-independent and agr-dependent manners.
Thymidine-Dependent Staphylococcus Aureus Small-Colony Variants Are Associated With Extensive Alterations In Regulator And Virulence Gene Expression Profiles, Barbara C. Kahl, Gunnar Belling, Petra Becker, Indranil Chatterjee, Katrin Wardecki, Karin Hilgert, Ambrose Cheung
Thymidine-Dependent Staphylococcus Aureus Small-Colony Variants Are Associated With Extensive Alterations In Regulator And Virulence Gene Expression Profiles, Barbara C. Kahl, Gunnar Belling, Petra Becker, Indranil Chatterjee, Katrin Wardecki, Karin Hilgert, Ambrose Cheung
Dartmouth Scholarship
Chronic airway infection is a hallmark of cystic fibrosis (CF) and many CF patients are infected persistently by Staphylococcus aureus. Thymidine-dependent trimethoprim-sulfamethoxazole (SXT)-resistant S. aureus small-colony variants (SCVs), often in combination with isogenic normal S. aureus phenotypes, are highly prevalent and persistent in airway secretions of CF patients due to long-term SXT therapy (B. Kahl, M. Herrmann, A. S. Everding, H. G. Koch, K. Becker, E. Harms, R. A. Proctor, and G.
Rat/Mgra, A Regulator Of Autolysis, Is A Regulator Of Virulence Genes In Staphylococcus Aureus, Susham Ingavale, Willem Van Wamel, Thanh T. Luong, Chia Y. Lee, Ambrose L. Cheung
Rat/Mgra, A Regulator Of Autolysis, Is A Regulator Of Virulence Genes In Staphylococcus Aureus, Susham Ingavale, Willem Van Wamel, Thanh T. Luong, Chia Y. Lee, Ambrose L. Cheung
Dartmouth Scholarship
We have previously identified mgrA (rat) as a regulator of autolysis in Staphylococcus aureus. Besides its effect on autolytic activity, we recently found alterations in the expression of regulator and target virulence genes in the mgrA mutant. Northern analysis and transcription fusion assays showed that inactivation of mgrA has led to the downregulation of RNAIII of agr and hla and upregulation of sarS and spa. Although both SarA and agr are activators of α-hemolysin and a repressors of protein A synthesis, we found that the transcription of sarA was not affected in the mgrA mutant and …
Impacts Of Sara And Agr In Staphylococcus Aureus Strain Newman On Fibronectin-Binding Protein A Gene Expression And Fibronectin Adherence Capacity In Vitro And In Experimental Infective Endocarditis, Yan-Qiong Xiong, Arnold S. Bayer, Michael R. Yeaman, Willem Van Wamel, Adhar C. Manna, Ambrose L. Cheung
Impacts Of Sara And Agr In Staphylococcus Aureus Strain Newman On Fibronectin-Binding Protein A Gene Expression And Fibronectin Adherence Capacity In Vitro And In Experimental Infective Endocarditis, Yan-Qiong Xiong, Arnold S. Bayer, Michael R. Yeaman, Willem Van Wamel, Adhar C. Manna, Ambrose L. Cheung
Dartmouth Scholarship
We investigated the impacts of sarA and agr on fnbA expression and fibronectin-binding capacity in Staphylococcus aureus in vitro and in experimental endocarditis. Although sarA up-regulated and agr down-regulated both fnbA expression and fibronectin binding in vitro and in vivo, fnbA expression was positively regulated in the absence of both global regulators. Thus, additional regulatory loci contribute to fnbA regulation and fibronectin-binding capacities in S. aureus.
Sart Influences Sars Expression In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Ambrose L. Cheung
Sart Influences Sars Expression In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Ambrose L. Cheung
Dartmouth Scholarship
Staphylococcus aureus is a gram-positive pathogen that is capable of expressing a variety of virulence proteins in response to environmental signals. Virulence protein expression in S. aureus is controlled by a network of regulatory loci including sarA and agr. The sarA/agr network is associated with the expression of cell wall-associated adhesins during exponential growth and the expression of secreted enzymes and toxins in the transition to post-exponential growth. A number of sarA homologs, including sarT and sarS, have been identified in the S. aureus genome. Previous studies have shown that sarA influences expression of both sarT and sarS in the …
Staphylococcus Aureus Agr And Sara Functions Are Required For Invasive Infection But Not Inflammatory Responses In The Lung, Geoffrey Heyer, Shahryar Saba, Robert Adamo, William Rush, Grace Soong, Ambrose Cheung, Alice Prince
Staphylococcus Aureus Agr And Sara Functions Are Required For Invasive Infection But Not Inflammatory Responses In The Lung, Geoffrey Heyer, Shahryar Saba, Robert Adamo, William Rush, Grace Soong, Ambrose Cheung, Alice Prince
Dartmouth Scholarship
Staphylococcus aureus strains lacking agr- and sarA-dependent gene products or specific MSCRAMM (microbial surface components recognizing adhesive matrix molecules) adhesins were compared for the ability to activate inflammatory responses in the lung. The mutants were evaluated for virulence in a mouse model of pneumonia and by quantifying their ability to stimulate interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in respiratory epithelial cells. In a neonatal mouse, only strains with intact agr and sarA loci were consistently associated with invasive, fatal pulmonary infection (P < 0.001) and sarA was specifically required to cause bacteremia (P < 0.001). The agr and/or sarA mutants were, nonetheless, fully capable of producing pneumonia and were as proficient as the wild-type strain in stimulating epithelial IL-8 expression, a polymorphonuclear leukocyte chemokine, in airway cells. In contrast, agr and especially sarA mutants induced less epithelial GM-CSF expression, and MSCRAMM mutants lacking fibronectin binding proteins or clumping factor A, a ligand for fibrinogen, were unable to stimulate epithelial GM-CSF production. The ability to induce IL-8 expression was independent of the adherence properties of intact bacteria, indicating that shed and/or secreted bacterial components activate epithelial responses. While conserved staphylococcal components such as peptidoglycan are sufficient to evoke inflammation and cause pneumonia, the agr and sarA loci of S. aureus are critical for the coordination of invasive infection of the lungs.