The MpsB protein contributes to both the toxicity and immune evasion capacity of Staphylococcus aureus

Understanding the role specific bacterial factors play in the development of severe disease in humans is critical if new approaches to tackle such infections are to be developed. In this study we focus on genes we have found to be associated with patient outcome following bacteraemia caused by the major human pathogen Staphylococcus aureus. By examining the contribution these genes make to the ability of the bacteria to survive exposure to the antibacterial factors found in serum, we identify three novel serum resistance-associated genes, mdeA, mpsB and yycH. Detailed analysis of an MpsB mutant supports its previous association with the slow growing small colony variant (SCV) phenotype of S. aureus, and we demonstrate that the effect this mutation has on membrane potential prevents the activation of the Agr quorum sensing system, and as a consequence the mutant bacteria do not produce cytolytic toxins. Given the importance of both toxin production and immune evasion for the ability of S. aureus to cause disease, we believe that these findings explain the role of the mpsB gene as a mortality-associated locus during human disease

The arsenal employed by <i>C</i>. <i>glabrata</i> to resist pharmaceutical interventions.

(A) The cell wall is the front line of battle between C. glabrata and antifungal drugs. Azoles target the plasma membrane, but resistance to azole drugs occurs through gain of function mutation in pdr1, which increases expression of drug efflux pumps. Polyenes bore into the plasma membrane paving the way for cytoplasmic contents, e.g., ions to leech into the extracellular space. Echinocandins target B-(1,3)-glucans. Resistance is consistently related to mutations in FKS genes, which normally govern B glucan synthesis. (B) Genomic flexibility drives adaptability and resistance in C. glabrata. Antifungal drug resistance correlates with increased telomere length and circularity of chromosomes. (C) Ploidy and aneuploidy drive genome plasticity by providing the framework through which the fungus makes genetic changes. (D) Biofilms adhere to biotic and abiotic surfaces, e.g., during mechanical ventilation. Due to varying cellular states and extracellular matrix, these entities are recalcitrant to therapeutics. Cells can slough off and result in systemic infection. This figure was created with Biorender.com.</p

Definitions of terms.

Candida glabrata: A powerhouse of resistanc

Defining the transcriptomic landscape of Candida glabrata by RNA-Seq

Candida glabrata is the second most common pathogenic Candida species and has emerged as a leading cause of nosocomial fungal infections. Its reduced susceptibility to antifungal drugs and its close relationship to Saccharomyces cerevisiae make it an interesting research focus. Although its genome sequence was published in 2004, little is known about its transcriptional dynamics. Here, we provide a detailed RNA-Seq-based analysis of the transcriptomic landscape of C. glabrata in nutrient-rich media, as well as under nitrosative stress and during pH shift. Using RNA-Seq data together with state-of-the-art gene prediction tools, we refined the annotation of the C. glabrata genome and predicted 49 novel protein-coding genes. Of these novel genes, 14 have homologs in S. cerevisiae and six are shared with other Candida species. We experimentally validated four novel protein-coding genes of which two are differentially regulated during pH shift and interaction with human neutrophils, indicating a potential role in host–pathogen interaction. Furthermore, we identified 58 novel non-protein-coding genes, 38 new introns and condition-specific alternative splicing. Finally, our data suggest different patterns of adaptation to pH shift and nitrosative stress in C. glabrata, Candida albicans and S. cerevisiae and thus further underline a distinct evolution of virulence in yeast