Table 3.

Annotation and Function of Notable Single-Nucleotide Polymorphisms (SNPs)

Patient	SNP Position	Gene	Codon	Effect	Amino Acid Change	Gene Name/Function	Category	Association
A	534 272	glmU	gGc/gAc	NS	G208D	Bifunctional N-acetylglucosamine-1-phosphate uridyltransferase	Cell wall and capsule	Key component of cell wall biosynthesis [18]
	941 455	glpQ	Cag/Tag	SG	Q125STOP	Glycerophosphoryl diester phosphodiesterase	Carbohydrates	…
	1 246 149	rnhB	aTa/aAa	NS	L64K	Ribonuclease HII	RNA metabolism	Degrades RNA of DNA-RNA hybrids
	1 302 306	SAUSA300_1182	tTg/tCg	NS	L511S	Pyruvate ferredoxin oxidoreductase, α subunit	Respiration	…
	1 449 721	msrA	Cca/Tca	NS	P23S	Methionine sulfoxide reductase A	Protein metabolism	Bacterial oxidative stress response [19]
	2 130 440	SAUSA300_1975	gAt/gGt	NS	D140G	Aerolysin/leukocidin family protein	Virulence, disease, and defense	…
	2 476 503	tcaR	Act/Cct	NS	T99P	Transcriptional regulator, TcaR	Virulence, disease, and defense	Important role in biofilm formation [20] and expression of virulence factors, including sarS and spa [21]
	2 857 261	nixA	Gca/Tca	NS	A285S	High-affinity nickel transporter	Membrane transport	Necessary for urease activity [22]
B	Population 1
	16 135	SAUSA300_0012	atG/atA	SL	M1I	Homoserine O-acetyltransferase	Amino acids and derivatives	Metabolism
	115 262	SAUSA300_0104	tAt/tGt	NS	Y569C	Transcriptional regulator, AraC	Regulation and cell signaling	…
	507 017	treC	gAa/gGa	NS	E437G	α-phosphotrehalase	Virulence, disease, and defense	…
	1 046 867	atl	Aaa/Taa	SG	K374STOP	Bifunctional autolysin	Virulence, disease, and defense	Cell wall metabolism and biofilm development
	2 705 337	SAUSA300_2500	gCa/gTa	NS	A259V	4,4′-diaponeurosporenoate glycosyl transferase	Membrane transport	Metabolism of terpenoids and polyketides
	Population 2
	2 149 492	agrA	aGa/aAa	NS	R170K	Accessory gene regulator protein A	Regulation and cell signaling	Regulates expression of several virulence genes and may have a role in biofilm production [23]
	2 746 919	SAUSA300_2542	aGt/aAt	NS	S323N	Putative AMP-binding enzyme	Regulation and cell signaling	May be linked to daptomycin nonsusceptibility [24]
	2 766 651	SAUSA300_2556	gCg/gTg	NS	A519V	ABC transporter protein	Membrane transport	Effluxing cytotoxic drugs across the cell membrane [25]
C	238 924	SAUSA300_0202	Gaa/Aaa	NS	E273K	Peptide ABC transporter permease	Membrane transport	Peptide ABC transporter permease [26]
	975 709	oppC	aTt/aAt	NS	I211N	Oligopeptide ABC transporter, permease protein	Membrane transport	Peptide ABC transporter permease [26]
	975 798	oppC	Aaa/Taa	SG	K241STOP	Oligopeptide ABC transporter, permease protein	Membrane transport	Peptide ABC transporter permease [26]
	1 263 354	pyrH	Atg/Ttg	NS	M207L	Uridylate kinase	Cofactors, vitamins, prosthetic groups, pigments	Involved in cell wall and RNA biosynthesis [27]
D	Population 1
	848 576	eno	Gta/Ata	NS	V119I	Phosphopyruvate hydratase	Amino acids and derivatives	Enhances the activation of plasminogen, assisting in tissue dissemination [28]
	1 181 644	ftsZ	gaC/gaA	NS	D31E	Cell division protein, FtsZ	Cell division and cell cycle	Essential for cell division [29]
	1 420 581	dapB	Tca/Aca	NS	S211T	Dihydrodipicolinate reductase	Amino acids and derivatives	Essential component for lysine biosynthesis [30]
	1 955 851	lukD	tCt/tGt	NS	S150C	Leukotoxin, LukD	Virulence, disease, and defense	Well-known cytotoxic virulence gene responsible for cell lyses [31]
	2 808 635	SAUSA300_2587	Cgt/Agt	NS	R57S	Accessory secretory protein, Asp1	Membrane transport	Cell-wall-associated protein involved in the pathogenesis [32]
	Population 2
	1 405 837	pepF	cCt/cTt	NS	P11L	Oligoendopeptidase F	Protein metabolism	Protein turnover [33]
	2 165 813	ilvD	aTg/aCg	NS	M313T	Dihydroxy-acid dehydratase	Amino acids and derivatives	Dehydratase required for isoleucine metabolism and isoleucyl tRNA limitation [34, 35]
	2 554 758	SAUSA300_2375	tGg/tAg	SG	W547STOP	Multidrug ABC transporter ATP-binding/permease	Membrane transport	ABC transporter ATP-binding permease [25]
	2 734 666	panC	Gaa/Aaa	NS	E203K	Pantoate–β-alanine ligase	Cofactors, vitamins, prosthetic groups, pigments	Essential component of CoA synthesis and has been reported as a putative antimicrobial target [36]

SNPs resulting in a putative change in protein function are listed by patient. The annotation includes the location in respect to the USA300_FPR3757 reference genome (accession CP000255), gene name, and location and effect of the amino acid change. Significantly more mutations were observed in genes associated with membrane transport. NS mutations occurring in genes coding for hypothetical proteins were excluded from this table but can be found in Supplementary File 1.

Abbreviations: NS, nonsynonymous; SG, stop gained; SL, stop lost; tRNA, transfer RNA.