## 1 Introduction  
_Staphylococcus aureus_ (_S. aureus_) infections cause an intense burden on healthcare throughout the world, as the methicillin-resistant _S. aureus_ (MRSA) strain accounts for a majority of the infections present in hospital environments [1]. Infections with MRSA are difficult to treat due to their resistance to multiple antibiotics and highly invasive nature [2]. In particular, USA300 is a MRSA strain that was first isolated in infections among football players in the state of Pennsylvania in the United States in 2000 and has since been discovered in Europe, South America and Australia [3; 4]. This invasive strain has been shown to cause infections in community-associated infections, especially in traditionally low risk groups such as children in daycare, inmates in prisons, and military officials [5]. Many _S. aureus_ infections, including those caused by USA300, can develop into persistent and recurrent infections such as endocarditis and biofilm infections due to the presence of bacterial persisters [6; 7].  
Persisters are quiescent organisms that survive exposure to bactericidal drugs and stresses but are still susceptible to drugs and stresses upon exiting dormancy [7]. Persisters are genetically identical to the rest of the population of cells but exhibit a phenotype that allows them to be drug-tolerant [7]. Most studies on persistence mechanisms are done in _Escherichia coli_ (_E. coli_). Thus far, pathways such as toxin-antitoxin, SOS response and DNA repair, signal transduction, membrane stress, energy production, phosphate metabolism, and protein degradation are important for persister formation [7].  
A majority of the literature that implicates mechanisms of persister formation in _S. aureus_ stems from understanding the development of small colony variants (SCVs) that are isolated in persistent infections from patients. The unstable nature of SCVs that revert back to the normal phenotype provides a mechanism for relapsing infections [8]. Earlier works suggest that electron transport and thymidylate biosynthesis were associated with SCV formation [9]. SCVs have defects in genes involved in the respiratory chain such as _hemB_, which is involved in hemin biosynthesis, and _menB_, which is involved in menaquinone production [9]. Additionally, _S. aureus_ can form cell-wall deficient bacteria called L-form bacteria, named after the Lister Institute, which is where these morphological variants were discovered, that can evade antibiotic activity and the host immune response [10]. Using a transposon mutant library of _S. aureus_ to identify mutants defective in unstable L-form formation, [PERSON] _et al._ identified that _g/pF_ involved in glycerol uptake was critical for L-form formation and persistence to antibiotics in _S. aureus_[11]. Although SCV and L-form bacteria are implicated in causing relapsing and persistent infections, the mechanisms of _S. aureus_ persister formation are largely unknown.  
Since the discovery of the persister phenomenon in Staphylococcal cultures in 1940s, there is renewed interest in understanding _S. aureus_ persistence and persister biology [7]. Here, we performed a systematic, high-throughput mutant screen against mutants of all non-essential genes in the clinically relevant USA300 _S. aureus_ strain to identify genes that play a role in bacterial persistence in _S. aureus_. Mutants involved in metabolite production or regulation were found to be required for bacterial persistence to stresses and antibiotics.