Genetics, Genomics and Pathogenesis of Staphylococcus aureus

Dear Colleagues,

Staphylococcus aureus is a versatile human and veterinary pathogenic bacterium recognized as a worldwide health problem. S. aureus is responsible for a wide spectrum of infections, ranging from local skin to severe disseminated diseases. In humans, these infections include acute diseases such as endocarditis, furunculosis or food poisoning but also chronic infections such as osteomyelitis, rhinosinusitis or otitis media. Nonetheless, approximately 20–30% of the general population carries S. aureus asymptomatically for decades.

Methicillin-resistant Staphylococcus aureus emerged rapidly after the introduction of methicillin and has become a worldwide problem in developed countries since the 1980s. Infections due to S. aureus (or MRSA) are particularly diverse in terms of host, infected tissues, as well as severity and are generally difficult to eradicate. The versatility of this pathogen could be explained by different adaptative strategies and virulence properties. For instance, S. aureus is capable of surviving in remarkably diverse environmental conditions (acidic, oxidant, non-physiological osmotic pressure, and desiccation, lack of nutrients and presence of host factors). S. aureus synthesizes a plethora of virulence factors, including cell-surface-associated proteins, toxins/exotoxins, and hydrolytic enzymes that facilitate attachment, colonization, and cell–cell interactions in various hosts. In addition, this organism can evade immune defenses by forming biofilm, through the induction of specific defense genes (catalase, superoxide dismutase, etc.) or by expressing immunomodulatory molecules allowing escape from host defenses. The roles of these bacterial compounds have been documented in part, in different experimental models of acute or chronic infections. The other factor that facilitates the invasive strategy is the ability of the bacterium to benefit from genome plasticity, allowing acquisition of foreign DNA, either from other species or from homologous bacterial species, enabling it to rapidly remodel its genome yielding to a super-bug genotype.

Despite this important diversity of clinical presentation and physiopathology, the totality of clinical manifestations and symptoms are due to only 8–10 different bacterial lineages. This observation suggests that the bacterium would be highly variable in terms of genomic features and ability to interact with a variety of compounds, niches, tissues or cells. These mechanisms are related to modulation of gene expression but also to intrinsic genome composition. The percentage of conserved open reading frames (ORFs) throughout the genomes represents roughly 75% of genes constituting the core genome. These include essential genes that encode cell survival functions, maintain housekeeping, facilitate bacterial central metabolism, and synthesize and replicate DNA and RNA. Conversely, 25% of the genomic content represents accessory genes. About half of these accessory genes consist of mobile genetic elements (MGEs) that play a central role in adaptation processes and in genetic evolution. Considering that approximately 50% of annotated genes have an unknown function, studies of the content and most importantly the expression of all S. aureus genomic features should contribute to document the steps required during bacteria and host interaction. The general regulatory processes at the level of the whole cell, mediating organized gene expression, also represent a major element considering S. aureus virulence. During the last 2 decades, dramatic improvements in high-throughput sequencing technology have allowed studying the diversity and content of some S. aureus populations representative of specific clinical settings and performing transcriptomic studies at the whole cell level to explore complex regulatory pathways during exposition to specific environments.

The aim of this Special Issue is to summarize the molecular mechanisms mainly driven by the accessory genome of S. aureus using genomic and transcriptomic methods, allowing us to improve our knowledge and comprehension of pathogenesis and physio-pathogenic aspects of S. aureus behavior in contact with an infected host.

Dr. Patrice Francois
Dr. Nathalie L. van Der Mee-Marquet
Guest Editors

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• Staphylococcus aureus
• genomics
• trancriptomic
• regulation
• virulence factors
• biofilm
• epidemiology
• human infection
• prophages
• genome plasticity
• virulence
• molecular mechanisms