Project description:The present work comprises the study of wound pathogenic bacteria as part of a community. It considers the interactions of two different S. aureus isolates with B. thuringiensis and K. oxytoca; all of them isolated from the same chronic wound of a patient with epidermolysis bullosa. Particular focus has been given on the interactions of S. aureus with other microbes due to its high prevalence among chronic wounds. During cultivation, no species performed as dominant or inhibited the growth of one another. Mass spectrometry was used to explore the inherent relationships between the staphylococcal strains and the coexisting bacteria exproteomes. The analysis showed an important reduction in the amount of staphylococcal cytoplasmic proteins when co-cultured with K. oxytoca and B. thuringiensis, this decrement did not occur with klebsiella and bacillus proteins. Interestingly, K. oxytoca and B. thuringiensis seemed to have a more evident response towards the presence of S. aureus in the culture, while the opposite was not observed with the staphylococcal isolates. Genomic analysis revealed isolate t13595 hypermutable characteristics, placing the interactions between staphylococcal isolates in the context of a chronic wound. Overall, the nature of the exoproteome variations among cultures suggests that adaptive mechanisms differ in all strains.
Project description:USA300 Staphylococcus aureus is responsible for the current outbreak of skin abscesses in the United States. Unlike other USA types, USA300 colonizes the rectum at rates higher than the nose. The reason for the difference in colonization site preference may be related to specific adherence or attachment factors contained in the genome of these strains. Additional knowledge in this field may help design novel prophylactic and therapeutic strategies to combat staphylococcal infections. Strains of USA300 MSSA and MRSA colonizing the nose and/or rectum from children with staphylococcal skin abscesses were compared by whole genome array technology to identify bacterial genetic determinants associated with site-specific colonization. Strains isolated from different colonization sites were indistinguishable by genomic content. Site-specific colonization traits were not detected in the colonizing bacteria by this array. Either host characteristics associated with staphylococcal carriage or under represented bacterial genomic constructions need to be examined to determine the etiology of this site-specific colonization. Data is also available from <ahref=http://bugs.sgul.ac.uk/E-BUGS-102 target=_blank>BuG@Sbase</a>
Project description:Staphylococcus aureus is a notorious biofilm-producing pathogen that is frequently isolated from implantable medical device infections. As biofilm ages, it becomes more tolerant to antimicrobial treatment leading to treatment failure and necessitating the costly removal of infected devices. In this study, we investigated what changes occur in the proteome of S. aureus biofilm grown for 3-days and 12-days in comparison with 24 h planktonic showed that proteins associated with bi-osynthetic processes, ABC transporter pathway, virulence proteins, and shikimate kinase pathway were significantly upregulated in 3-day biofilm, while proteins associated with sugar transporter, degradation, and stress response were downregulated. In 12-day biofilms, proteins associated with peptidoglycan biosynthesis, sugar transporters, and stress responses were upregulated, whereas proteins associated with ABC transporters, DNA replication, and adhesion proteins were down-regulated. Furthermore, we observed significant variations in the formation of biofilms result from changes in the level of metabolic activity in the different growth mode of biofilms that could be a significant factor of S. aureus biofilm maturation and persistence. Collectively, potential marker proteins were identified and further characterized to understand their exact role in S. aureus biofilm development which may shed light on possible new therapeutic regimes in the treatment of biofilm-related implant-associated infections.
Project description:Staphylococcus aureus is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment. Antibiotic tolerance, the ability of bacteria to persist despite normally lethal doses of antibiotics, contributes to antibiotic treatment failure in S. aureus infections. To understand how antibiotic tolerance is induced, S. aureus biofilms exposed to multiple anti-staphylococcal antibiotics were examined using both quantitative proteomics and transposon sequencing. These screens indicated that arginine metabolism is involved in antibiotic tolerance within a biofilm and led to the hypothesis that depletion of arginine within S. aureus communities can induce antibiotic tolerance. Consistent with this hypothesis, inactivation of argH, the final gene in the arginine synthesis pathway, induces antibiotic tolerance. Arginine restriction was found to induce antibiotic tolerance via inhibition of protein synthesis. In a mouse skin infection model, an argH mutant has enhanced ability to survive antibiotic treatment with vancomycin, highlighting the relationship between arginine metabolism and antibiotic tolerance during S. aureus infection. Uncovering this link between arginine metabolism and antibiotic tolerance has the potential to open new therapeutic avenues targeting previously recalcitrant S. aureus infections.
2024-07-10 | GSE267626 | GEO
Project description:Novel human-associated staphylococcal species
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is problematic both in hospitals and the community. Currently, we have limited understanding of mechanisms of innate immune evasion used by S. aureus. To that end, we created an isogenic deletion mutant in strain MW2 (USA400) of the saeR/S two-component gene regulatory system and studied its role in mouse models of pathogenesis and during human neutrophil interaction. In this study, we demonstrate saeR/S plays a distinct role in S. aureus pathogenesis and is vital for virulence of MW2 in a mouse model of sepsis. Moreover, deletion of saeR/S significantly impaired survival of MW2 in human blood and after neutrophil phagocytosis. Microarray analysis of genes influenced by saeR/S demonstrated SaeR/S of MW2 influences a wide variety of genes with diverse biological functions. These data shed new insight into how virulence is regulated in S. aureus and associates a specific staphylococcal gene-regulatory system with invasive staphylococcal disease. Wild type control vs mutant at two different growth phases