scholarly journals Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for Vaccine and Therapeutics

2018 ◽  
Vol 19 (2) ◽  
pp. 111-127 ◽  
Author(s):  
Trevor L. Kane ◽  
Katelyn E. Carothers ◽  
Shaun W. Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factor ◽  
Bacterial Pathogen

scholarly journals Staphylococcus aureus Resistance to Human Defensins and Evasion of Neutrophil Killing via the Novel Virulence Factor Mprf Is Based on Modification of Membrane Lipids with l-Lysine

2001 ◽  
Vol 193 (9) ◽  
pp. 1067-1076 ◽  
Author(s):  
Andreas Peschel ◽  
Ralph W. Jack ◽  
Michael Otto ◽  
L. Vincent Collins ◽  
Petra Staubitz ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptides ◽  
Virulence Factor ◽  
Membrane Lipids ◽  
Membrane Surface ◽  
Resistance Mechanism ◽  
Bacterial Pathogen ◽  
Human Neutrophils ◽  
Resistant Bacteria ◽  
Host Defense Peptides

Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance mechanism. We describe a novel staphylococcal gene, mprF, which determines resistance to several host defense peptides such as defensins and protegrins. An mprF mutant strain was killed considerably faster by human neutrophils and exhibited attenuated virulence in mice, indicating a key role for defensin resistance in the pathogenicity of S. aureus. Analysis of membrane lipids demonstrated that the mprF mutant no longer modifies phosphatidylglycerol with l-lysine. As this unusual modification leads to a reduced negative charge of the membrane surface, MprF-mediated peptide resistance is most likely based on repulsion of the cationic peptides. Accordingly, inactivation of mprF led to increased binding of antimicrobial peptides by the bacteria. MprF has no similarity with genes of known function, but related genes were identified in the genomes of several pathogens including Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Enterococcus faecalis. MprF thus constitutes a novel virulence factor, which may be of general relevance for bacterial pathogens and represents a new target for attacking multidrug resistant bacteria.

scholarly journals Virulence factor landscape of a Staphylococcus aureus sequence type 45 strain, MCRF184

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Vijay Aswani ◽  
Fares Najar ◽  
Madhulatha Pantrangi ◽  
Bob Mau ◽  
William R. Schwan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factor ◽  
Sequence Type

sae is essential for expression of the staphylococcal adhesins Eap and Emp

Microbiology ◽  
2005 ◽  
Vol 151 (6) ◽  
pp. 1789-1800 ◽  
Author(s):  
Niamh Harraghy ◽  
Jan Kormanec ◽  
Christiane Wolz ◽  
Dagmar Homerova ◽  
Christiane Goerke ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Extracellular Matrix ◽  
Virulence Factor ◽  
Eukaryotic Cells ◽  
Transcription Start Point ◽  
Chronic Infections ◽  
Transcription Start ◽  
Regulatory Mutants ◽  
Global Regulators ◽  
Glucose Analysis

Eap and Emp are two Staphylococcus aureus adhesins initially described as extracellular matrix binding proteins. Eap has since emerged as being important in adherence to and invasion of eukaryotic cells, as well as being described as an immunomodulator and virulence factor in chronic infections. This paper describes the mapping of the transcription start point of the eap and emp promoters. Moreover, using reporter-gene assays and real-time PCR in defined regulatory mutants, environmental conditions and global regulators affecting expression of eap and emp were investigated. Marked differences were found in expression of eap and emp between strain Newman and the 8325 derivatives SH1000 and 8325-4. Moreover, both genes were repressed in the presence of glucose. Analysis of expression of both genes in various regulatory mutants revealed that sarA and agr were involved in their regulation, but the data suggested that there were additional regulators of both genes. In a sae mutant, expression of both genes was severely repressed. sae expression was also reduced in the presence of glucose, suggesting that repression of eap and emp in glucose-containing medium may, in part, be a consequence of a decrease in expression of sae.

Impact ofd-amino acid dehydrogenase on virulence factor production by aPseudomonas aeruginosa

2013 ◽  
Vol 59 (9) ◽  
pp. 598-603 ◽  
Author(s):  
Kathryn E. Oliver ◽  
Laura Silo-Suh
Keyword(s):  
Amino Acid ◽  
Virulence Factor ◽  
Bacterial Pathogen ◽  
Optimal Production ◽  
Acid Dehydrogenase ◽  
Amino Acid Dehydrogenase ◽  
Factor Production ◽  
Lung Dysfunction ◽  
Production Of Hydrogen ◽  
Virulence Factor Production

Chronic Pseudomonas aeruginosa infections remain the leading cause of lung dysfunction and mortality for cystic fibrosis (CF) patients. Many other bacteria inhabit the CF lung, but P. aeruginosa utilizes novel strategies that allow it to colonize this environment as the predominant bacterial pathogen. d-Amino acid dehydrogenase encoded by dadA is highly expressed by P. aeruginosa within the CF lung, and it is required for optimal production of hydrogen cyanide by some CF-adapted isolates. To better understand the increased significance of d-amino acid dehydrogenase in P. aeruginosa physiology, we characterized the contribution of the dad operon to virulence factor production. In this study, we determined that DadA is required for optimal production of pyocyanin, pyoverdine, and rhamnolipid by CF-adapted and non-CF-adapted isolates of P. aeruginosa. In addition, DadA is required for optimal production of alginate, biofilm formation, and virulence of a CF-adapted isolated of P. aeruginosa in an alfalfa seedling model of infection. Taken together, the results indicate that DadA plays a pleiotropic role in the production of important virulence factors by P. aeruginosa.

scholarly journals Total Synthesis of Xanthoangelol B and Its Various Fragments: Toward Inhibition of Virulence Factor Production of Staphylococcus aureus

2018 ◽  
Vol 61 (23) ◽  
pp. 10473-10487 ◽  
Author(s):  
Pushpak Mizar ◽  
Rekha Arya ◽  
Truc Kim ◽  
Soyoung Cha ◽  
Kyoung-Seok Ryu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Total Synthesis ◽  
Virulence Factor ◽  
Factor Production ◽  
Virulence Factor Production

scholarly journals Discovery of genes encoding a Streptolysin S-like toxin biosynthetic cluster in a select highly pathogenic methicillin resistant Staphylococcus aureus JKD6159 strain

2019 ◽  
Author(s):  
Trevor Kane ◽  
Katelyn E. Carothers ◽  
Yunjuan Bao ◽  
Won-Sik Yeo ◽  
Taeok Bae ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gene Cluster ◽  
Virulence Factor ◽  
Gene Organization ◽  
Biosynthetic Gene ◽  
Bacterial Gene ◽  
Methicillin Resistant ◽  
Streptolysin S

AbstractBackgroundStaphylococcus aureus (S. aureus) is a major human pathogen owing to its arsenal of virulence factors, as well as its acquisition of multi-antibiotic resistance. Here we report the identification of a Streptolysin S (SLS) like biosynthetic gene cluster in a highly virulent community-acquired methicillin resistant S. aureus (MRSA) isolate, JKD6159. Examination of the SLS-like gene cluster in JKD6159 shows significant homology and gene organization to the SLS-associated biosynthetic gene (sag) cluster responsible for the production of the major hemolysin SLS in Group A Streptococcus.ResultsWe took a comprehensive approach to elucidating the putative role of the sag gene cluster in JKD6159 by constructing a mutant in which one of the biosynthesis genes (sagB homologue) was deleted in the parent JKD6159 strain. Assays to evaluate bacterial gene regulation, biofilm formation, antimicrobial activity, as well as complete host cell response profile and comparative in vivo infections in Balb/Cj mice were conducted.ConclusionsAlthough no significant phenotypic changes were observed in our assays, we postulate that the SLS-like toxin produced by this strain of S. aureus may be a highly specialized virulence factor utilized in specific environments for selective advantage; studies to better understand the role of this newly discovered virulence factor in S. aureus warrant further investigation.

scholarly journals MODERN APPROACHES TO ANTIVIRULENT THERAPY OF DISEASES ASSOCIATED WITH STAPHYLOCOCCUS AUREUS

2019 ◽  
Vol 23 (3-4) ◽  
pp. 26-31
Author(s):  
T.O. Kryuchko ◽  
O.Ya. Tkachenko ◽  
N.V. Kuzmenko ◽  
I.N. Nesina ◽  
S.M. Tanianska ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Effective Means ◽  
Bacterial Pathogen ◽  
Cross Reactivity ◽  
Main Function ◽  
Virulence Proteins ◽  
New Antibiotics ◽  
Active Research

Staphylococcus aureus is a universal bacterial pathogen, which is able to develop the resistance to new antibiotics, by means of virulence factors, whose main function is the spread of diseases by inhibiting the immune factors of host defense. Its wide spread at in-patient departments and also the presence of clinical probationary wards Staphylococcus aureus, resistant to methicillin at out-patient departments, deprive the doctors of effective means for control of the infection. Complications caused by MRSA lead to hospitalization and indices of lethality. The aim of the paper is to analyze the main factors of S. аureus virulence and ways the of its interaction as a result of etiological and pathogenetic treatment. Complexity of treatment of bacterial infections is determined by alternative ways of prevention and treatment of diseases to which bacteria are not able to develop resistance. Along with general mechanisms that form antibiotic resistance, S. aureus produces many individual virulence factors that model the immune response, affecting the survival of the microorganism. The virulence factors produced by S. aureus are diverse and have the ability not only to cause cell lysis, but also to stimulate tissue rejection and destruction. It is important to determine that many specific factors of virulence caused by S. aureus, have ability to change both congenital and adaptive immune reactions including inhibition of complement activation, neutrophils neutralization, phagocytes inhibition. Strategies for inhibiting virulence factors can range from using small inhibitor molecules or full-fledged antibodies to creating toxoids and virulence proteins. Great interest is focused upon those inhibitors that have cross-reactivity with respect to multiple virulence factors, as well as inhibitors, the main target of which is a global regulator with multi-purpose activity, for example, agr operon. Active research into the specific alternative antivirulent treatments for severe diseases caused by S. aureus can potentially settle a number of problems and difficulties of post-antibiotic era.

scholarly journals Candida albicans and Staphylococcus aureus Pathogenicity and Polymicrobial Interactions: Lessons beyond Koch’s Postulates

2019 ◽  
Vol 5 (3) ◽  
pp. 81 ◽  
Author(s):  
Olivia A. Todd ◽  
Brian M Peters
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Sequence Data ◽  
Bacterial Pathogen ◽  
Toxin Production ◽  
Microbial Interactions ◽  
Human Pathogens ◽  
Koch’S Postulates ◽  
Bacterial Interaction ◽  
Koch's Postulates

While Koch’s Postulates have established rules for microbial pathogenesis that have been extremely beneficial for monomicrobial infections, new studies regarding polymicrobial pathogenesis defy these standards. The explosion of phylogenetic sequence data has revolutionized concepts of microbial interactions on and within the host. However, there remains a paucity of functional follow-up studies to delineate mechanisms driven by such interactions and how they shape health or disease. That said, one particular microbial pairing, the fungal opportunist Candida albicans and the bacterial pathogen Staphylococcus aureus, has received much attention over the last decade. Therefore, the objective of this review is to discuss the multi-faceted mechanisms employed by these two ubiquitous human pathogens during polymicrobial growth, including how they: establish and persist in inter-Kingdom biofilms, tolerate antimicrobial therapy, co-invade host tissue, exacerbate quorum sensing and staphylococcal toxin production, and elicit infectious synergism. Commentary regarding new challenges and remaining questions related to future discovery of this fascinating fungal–bacterial interaction is also provided.

scholarly journals The ClpCP Complex Modulates Respiratory Metabolism inStaphylococcus aureusand Is Regulated in a SrrAB-Dependent Manner

2019 ◽  
Vol 201 (15) ◽  
Author(s):  
Ameya A. Mashruwala ◽  
Brian J. Eilers ◽  
Amanda L. Fuchs ◽  
Javiera Norambuena ◽  
Carly A. Earle ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Energy Metabolism ◽  
Energy Homeostasis ◽  
Protein Complexes ◽  
Present Report ◽  
Bacterial Pathogen ◽  
Dependent Manner ◽  
Content Type ◽  
Fermentative Growth ◽  
Increased Sensitivity

ABSTRACTThestaphylococcalrespiratoryregulator (SrrAB) modulates energy metabolism inStaphylococcus aureus. Studies have suggested that regulated protein catabolism facilitates energy homeostasis. Regulated proteolysis inS. aureusis achieved through protein complexes composed of a peptidase (ClpQ or ClpP) in association with an AAA+family ATPase (typically, ClpC or ClpX). In the present report, we tested the hypothesis that SrrAB regulates a Clp complex to facilitate energy homeostasis inS. aureus. Strains deficient in one or more Clp complexes were attenuated for growth in the presence of puromycin, which causes enrichment of misfolded proteins. A ΔsrrABstrain had increased sensitivity to puromycin. Epistasis experiments suggested that the puromycin sensitivity phenotype of the ΔsrrABstrain was a result of decreased ClpC activity. Consistent with this, transcriptional activity ofclpCwas decreased in the ΔsrrABmutant, and overexpression ofclpCsuppressed the puromycin sensitivity of the ΔsrrABstrain. We also found that ClpC positively influenced respiration and that it did so upon association with ClpP. In contrast, ClpC limited fermentative growth, while ClpP was required for optimal fermentative growth. Metabolomics studies demonstrated that intracellular metabolic profiles of the ΔclpCand ΔsrrABmutants were distinct from those of the wild-type strain, supporting the notion that both ClpC and SrrAB affect central metabolism. We propose a model wherein SrrAB regulates energy homeostasis, in part, via modulation of regulated proteolysis.IMPORTANCEOxygen is used as a substrate to derive energy by the bacterial pathogenStaphylococcus aureusduring infection; however,S. aureuscan also grow fermentatively in the absence of oxygen. To successfully cause infection,S. aureusmust tailor its metabolism to take advantage of respiratory activity. Different proteins are required for growth in the presence or absence of oxygen; therefore, when cells transition between these conditions, several proteins would be expected to become unnecessary. In this report, we show that regulated proteolysis is used to modulate energy metabolism inS. aureus. We report that the ClpCP protein complex is involved in specifically modulating aerobic respiratory growth but is dispensable for fermentative growth.

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