scholarly journals An engineered protein-based submicromolar competitive inhibitor of the Staphylococcus aureus virulence factor aureolysin

Author(s):  
Soraia R. Mendes ◽  
Ulrich Eckhard ◽  
Arturo Rodríguez-Banqueri ◽  
Tibisay Guevara ◽  
Peter Czermak ◽  
...  
BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Vijay Aswani ◽  
Fares Najar ◽  
Madhulatha Pantrangi ◽  
Bob Mau ◽  
William R. Schwan ◽  
...  

Microbiology ◽  
2005 ◽  
Vol 151 (6) ◽  
pp. 1789-1800 ◽  
Author(s):  
Niamh Harraghy ◽  
Jan Kormanec ◽  
Christiane Wolz ◽  
Dagmar Homerova ◽  
Christiane Goerke ◽  
...  

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.


2018 ◽  
Vol 61 (23) ◽  
pp. 10473-10487 ◽  
Author(s):  
Pushpak Mizar ◽  
Rekha Arya ◽  
Truc Kim ◽  
Soyoung Cha ◽  
Kyoung-Seok Ryu ◽  
...  

2019 ◽  
Author(s):  
Trevor Kane ◽  
Katelyn E. Carothers ◽  
Yunjuan Bao ◽  
Won-Sik Yeo ◽  
Taeok Bae ◽  
...  

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.


2015 ◽  
Vol 197 (23) ◽  
pp. 3666-3675 ◽  
Author(s):  
Mei G. Lei ◽  
Chia Y. Lee

ABSTRACTStaphylococcus aureuscapsule is an important virulence factor that is regulated by a large number of regulators. Capsule genes are expressed from a major promoter upstream of thecapoperon. A 10-bp inverted repeat (IR) located 13 bp upstream of the −35 region of the promoter was previously shown to affect capsule gene transcription. However, little is known about transcriptional activation of thecappromoter. To search for potential proteins which directly interact with thecappromoter region (Pcap), we directly analyzed the proteins interacting with the PcapDNA fragment from shifted gel bands identified by electrophoretic mobility shift assay. One of these regulators, RbsR, was further characterized and found to positively regulatecapgene expression by specifically binding to thecappromoter region. Footprinting analyses showed that RbsR protected a DNA region encompassing the 10-bp IR. Our results further showed thatrbsRwas directly controlled by SigB and that RbsR was a repressor of therbsUDKoperon, involved in ribose uptake and phosphorylation. The repression ofrbsUDKby RbsR could be derepressed byd-ribose. However,d-ribose did not affect RbsR activation of capsule.IMPORTANCEStaphylococcus aureusis an important human pathogen which produces a large number of virulence factors. We have been using capsule as a model virulence factor to study virulence regulation. Although many capsule regulators have been identified, the mechanism of regulation of most of these regulators is unknown. We show here that RbsR activates capsule by direct promoter binding and that SigB is required for the expression ofrbsR. These results define a new pathway wherein SigB activates capsule through RbsR. Our results further demonstrate that RbsR inhibits therbsoperon involved in ribose utilization, thereby providing an example of coregulation of metabolism and virulence inS. aureus. Thus, this study further advances our understanding of staphylococcal virulence regulation.


2019 ◽  
Vol 113 (1) ◽  
pp. 103-122 ◽  
Author(s):  
Heidi A. Crosby ◽  
Nitija Tiwari ◽  
Jakub M. Kwiecinski ◽  
Zhen Xu ◽  
Allison Dykstra ◽  
...  

2008 ◽  
Vol 57 (4) ◽  
pp. 403-410 ◽  
Author(s):  
P. Sauer ◽  
J. Síla ◽  
T. Štosová ◽  
R. Večeřová ◽  
P. Hejnar ◽  
...  

A rather fast and complicated progression of an infection caused by some strains of Staphylococcus aureus could be associated with the expression and co-action of virulence factor complexes in these strains. This study screened the antibiotic susceptibility and prevalence of virulence markers in isolates of meticillin-resistant S. aureus (MRSA) obtained from patients hospitalized at the University Hospital in Olomouc, Czech Republic. A total of 100 isolates was screened for 13 genes encoding extracellular virulence determinants (tst, pvl, eta, etb, sea, seb, sec, sed, see, seg, seh, sei and sej) and for their distribution in sample types. Eighty-nine isolates were positive for at least one of the genes. Genes for etb, pvl, see and seh were not detected in any of the MRSA isolates. No statistically significant differences in the occurrence of the determinants studied among sample types were found.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Amos Nworie ◽  
Azi S. Onyema ◽  
Simon I. Okekpa ◽  
Michael O. Elom ◽  
Nse O. Umoh ◽  
...  

Background. The changing epidemiology of methicillin-resistantStaphylococcus aureus(MRSA) from a hospital-associated pathogen to an organism commonly found in the community and in livestock reflects an organism well-equipped to survive in diverse environments and adjust to different environmental conditions including antimicrobial use.Methods. We investigated the molecular epidemiology ofS. aureusand MRSA in poultry in Ebonyi State, Nigeria. Samples were collected from 1800 birds on 9 different farms within the state. Positive isolates were tested for antibiotic susceptibility and molecular typing.Results. Prevalence in birds was 13.7% (247/1800). MRSA prevalence in poultry was 0.8%. The prevalence of MRSA in broilers and layers was 1.2% and 0.4%, respectively. All tested isolates were susceptible to vancomycin. Molecular analysis of the isolates revealed 3spatypes: t002, t084, and a novelspatype, t11469. The novelspatype t11469 belonged to sequence type ST5.Conclusion. The detection of t002 in chicken suggests the presence of livestock-associated MRSA in poultry in Ebonyi State. The detection of the newspatype t11469 in poultry that has not been characterised to ascertain its pathogenic potential remains a cause for concern, especially as some were found to carry PVL genes, a putative virulence factor in staphylococcal infection.


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