RNA sequencing and gene analysis of unstimulated and stimulated MRSA cultures
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ABSTRACT:
ORGANISM(S): Staphylococcus aureus
PROVIDER: GSE161844 | GEO | 2020/11/20
REPOSITORIES: GEO
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Project description:RNA sequencing and gene analysis of unstimulated and stimulated MRSA cultures
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Project description:Previous studies have documented the diversity of genetic background of methicillin-resistant S. aureus (MRSA) strains associated with healthcare (HA-MRSA), community (CA-MRSA) and livestock (LA-MRSA). The accessory and core-variable genome content of those strains remain largely unknown. To compare the composition of accessory and core-variable genome of Belgian MRSA strains according to host, population setting and genetic background, representative strains of HA- (n=21), CA- (n = 13) and ST398 LA-MRSA (n = 18) were characterized by a DNA-microarray (StaphVar Array) composed of oligonucleotide probes targeting ~400 resistance, adhesion and virulence associated genes.ST398 strains displayed very homogenous hybridization profiles (>94% gene content homology) irrespective of their host origin. This “ST398-specific” genomic profile was not distantly demarked from those of certain human-associated lineages but lacked several virulence- and colonization-associated genes harbored by strains of human origin, such as genes encoding proteases, haemolysins or adhesins. No enterotoxin gene was found among ST398 strains. In conclusion, our findings are consistent with a non-human origin of this ST398 lineage but suggest that it might have the potential to adapt further to the human host.
2010-11-15 | GSE20541 | GEO
Project description:A strategy for the high-throughput screening of a peptide nucleic acid (PNA) encoded peptide library to allow the identification of MRSA and MSSA selective peptides including AMPs. This novel screening approach allows simultaneous screening of cell selective peptides with different uptake mechanisms including lytic peptides and non-lytic CPPs. MRSA and MSSA were incubated with Library-18 (50 uM; corresponding to 39 nM of each library member) under short incubation times (30 min) to ensure collection of both live and apoptotic cells, which allowed selection of lytic peptides as well as non-lytic CPPs. Incubation was followed by washing and lysis and the intracellular and membrane associated library members were extracted and purified by filter centrifugation (between 3,000 and 10,000 Da). The extracted PNA tags were hybridized onto custom designed microarrays. Each microarray consisted of 4 sub-arrays of 44,000 features each with 33 replicates of each oligonucleotide complementary to each member of the library as well as 1232 non-coding negative controls. Microarray scanning and data analysis (BlueFuse, BlueGenome) was used to extract the intensity of the FAM label, thereby giving the relative amount of PNA hybridized to each spot and the identity of the peptide.
2012-12-01 | E-MEXP-3327 | biostudies-arrayexpress
Project description:Functionality of the accessory gene regulator (agr) quorum sensing system is an important switch promoting either acute or chronic infections, mediated by the notorious opportunistic human and veterinary pathogen Staphylococcus aureus. Spontaneous alterations of the agr system are known to frequently occur in human healthcare-associated S. aureus lineages. However, data on agr integrity and function are sparse regarding other major lineages. Here we report on the agr system functionality and activity level in mecC-carrying methicillin resistant S. aureus (MRSA) of various animal origins (n=33) in Europe together with closely related isolates of human patients (n=12). Whole genome analysis assigned all isolates to four clonal complexes (CC) with distinct agr types (CC599 agr I, CC49 agr II, CC130 agr III and CC1943 agr IV). Different levels of agr functionality were detected by use of different phenotype assays and proteomics for isolates of each CC, including completely non-functional variants. Genomic comparison of the agr I-IV encoding regions revealed that variants of AgrA and AgrC were associated with these phenotype changes, especially among the isolates of pet- and wild animal origin. Since a role in adaptation is most likely when genomic changes occur independently in divergent lineages, agr variation might foster viability and niche adjustment capacities of rare MRSA lineages.
2021-09-09 | PXD016486 | Pride
Project description:The success of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) as pathogens is due to a combination of antibiotic resistance with high virulence. However, evolution of the exceptional virulence potential of CA-MRSA is not understood. Our previous study indicated that differential gene expression contributes substantially to this process. Thus, we here investigated the role of the pivotal virulence gene regulatory system agr in the most prevalent CA-MRSA strain USA300. Using a mouse subcutaneous infection model, we show that agr is essential for the development of CA-MRSA skin infections, the most frequent manifestation of disease caused by CA-MRSA. Furthermore, genome-wide analysis of gene expression revealed significant differences in agr-dependent virulence gene regulation between CA-MRSA, HA-MRSA, and laboratory strains. Our findings demonstrate that agr functionality is critical for CA-MRSA disease and indicate that an adaptation of the agr regulon to optimize expression of a broad set of virulence determinants may have contributed to the evolution of exceptionally pronounced virulence of CA-MRSA strains. Keywords: wild type vs mutant
2011-03-29 | GSE18793 | GEO
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a major threat to human health. Rather than depend on creating new antibiotics (to which bacteria will eventually become resistant), we are employing antibiotic adjuvants that potentiate existing antibiotics. Based on our previous work, loratadine, the FDA-approvide antihistamine, effectively potentiates cell-wall active antibiotics in multiple strains of MRSA. Furthermore, loratadine and oxacillin helped disrupt preformed biofilms and stop them from initially forming in vitro. To gain biological insight into how this potentiation and biofilm inhibition occurs, we used RNA-seq on treated MRSA 43300 cultures to examine antibiotic adjuvant affects transcritome-wide.
2023-03-23 | GSE227099 | GEO
Project description:Influenza-induced respiratory failure is substantially worsened by secondary bacterial infections such as methicillin-resistant Staphylococcus aureus (MRSA). The bidirectional interaction between the influenza-injured lung microenvironment and MRSA is poorly understood. By conditioning MRSA ex vivo in bronchoalveolar lavage (BAL) fluid collected from mice at various timepoints of influenza infection, we found that influenza-injured lung microenvironment induces MRSA to increase cytotoxin expression while decreasing metabolic pathways. This overall increase in MRSA virulence was dependent upon SaeRS, a bacterial two-component system. Once expressed by MRSA, these influenza-induced toxins (such as Hla and LukAB) interact with host heparan sulfate (HS) fragments shed into the airspace. Highly-sulfated HS fragments augmented Hla- and LukAB-toxicity in vitro and in vivo. Our findings indicate that post-influenza MRSA pneumonia is shaped by bidirectional host-pathogen interactions: host injury triggers changes in bacterial expression of toxins, the activity of which are then shaped by host-derived HS fragments.
2022-11-29 | GSE199708 | GEO
Project description:Halogenated 4-hydroxybenzylidene indolinones have been shown to re-sensitize methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE) to methicillin and vancomycin respectively. The mechanism of antibiotic re-sensitization was however not previously studied. Here, we present the global proteomics analysis of S. aureus treated with GW5074, a 4-hydroxybenzylidene indolinone compound. Global proteomics analysis revealed that GW5074 treatment resulted in the downregulation of AgrC (a quorum sensing-related histidine kinase), AgrA (a quorum sensing-related response regulator) as well as downstream targets, such as hemolysins, lipases and proteases in S. aureus. Significant downregulation of enzymes involved in the purine biosynthesis was also observed. S. aureus proteins involved in amino acid metabolism and peptide transport were observed to be downregulated. The most upregulated protein was the lytic transglycosylase, SceD. These findings shed insights into how 4-hydroxybenzylidene indolinones kill bacteria and also re-sensitize MRSA to other antibiotics.
2018-11-28 | MSV000083170 | MassIVE
Project description:Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat to human health throughout the world. Rodent MRSA pneumonia models mainly focus on the early innate immune responses to MRSA infection. However, the molecular pattern and mechanisms of recovery from MRSA lung infection are largely unknown. In this study, a nonlethal mouse MRSA pneumonia model was employed to investigate events during lung recovery from MRSA infection. We compared lung bacterial clearance, bronchoalveolar lavage fluid (BALF) characterization, lung histology, and gene expression profiling between Day 1 and Day 3 post-MRSA infection. Compared to Day 1 post-infection, bacterial colony counts and both BALF total cell number and protein concentration significantly decreased at Day 3 post-infection. Lung cDNA microarray analysis identified 47 significantly up-regulated and 35 down-regulated genes (p<0.01, 1.5-fold change [up and down]). Changes in eight genes were confirmed by real-time PCR. The pattern of gene expression suggests lung recovery is characterized by enhanced cell division, vascularization, and wound healing and by adjustment in host adaptive immune responses. Collectively, this data helps elucidate the molecular mechanisms of lung recovery after MRSA infection.
2013-11-12 | GSE36587 | GEO
Project description:Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is life-threatening and occurs in up to 30% of MRSA bacteremia cases despite appropriate antimicrobial therapy. Isolates of MRSA that cause antibiotic-persistent MRSA bacteremia (APMB) typically have in vitro antibiotic susceptibilities equivalent to those causing antibiotic-resolving MRSA bacteremia (ARMB). Thus, persistence reflects host-pathogen interactions occurring uniquely in context of antibiotic therapy in vivo. However, host factors and mechanisms involved in APMB remain unclear. We compared DNA methylomes in circulating immune cells from patients experiencing APMB vs. ARMB. Overall, methylation signatures diverged in the distinct patient cohorts. Differentially methylated sites intensified proximate to transcription factor binding sites, primarily in enhancer regions. In APMB patients, significant hypo-methylation was observed in binding sites for CCAAT enhancer binding protein (C/EBP) and signal transducer / activator of transcription 1 (STAT1). In contrast, hypo-methylation in ARMB patients localized to glucocorticoid receptor and histone acetyltransferase p300 binding sites. These distinct methylation signatures were enriched in neutrophils and achieved a mean area under the curve of 0.85 when used to predict APMB using a classification model. These findings differentiate epigenotypes in patients experiencing APMB vs. ARMB, and suggest a risk stratification strategy for antibiotic persistence in patients treated for MRSA bacteremia.
2021-03-01 | GSE150144 | GEO