TABLE 4.

Correlation between PBP2X codon sites with signatures of positive selection and altered β-lactam susceptibility

Site	Substitution(s)a	dN/dS	Bayes (dS < dN)	Lineage(s)	Homplasic	MIC pen Gb	MIC change
274	Phe→Leu	2.329	5.272	2	No	–	–
288	Gly→Ser*	1.568	3.843	2	Yes	0.032	2.00
342	Met→Ile*	1.441	6.309	6	Yes	0.023	1.44
425	Phe→Leu	0.911	2.117	1	No	–	–
438	Ala→Thr	0.887	2.027	2	No	–	–
	Ala→Val			1		–	–
461	Thr→Pro	1.343	2.751	1	No	–	–
526	Pro→Leu	1.386	3.547	1	No	–	–
553	Thr→Lys*	1.474	3.698	2	Yes	0.023	1.44
593	Met→Leu*	3.398	12.301	2	Yes	0.032	2.00
	Met→Thr			6		0.032	2.00
	Met→Val*			6		0.032	2.00
600	Gly→Asp*	0.762	0.519	6	Yes	0.023	1.44
601	Pro→His*	34.421	12123	3	Yes	0.032	2.00
	Pro→Leu			10		0.032	2.00
	Pro→Ser*			1		0.016	1.00

^a*, new isogenic strains constructed in this study; M₅₉₃T and P₆₀₁L mutants were described previously (30, 31).

^bMICs provided for 10 PBP2X isogenic constructs with the fold change relative to the parent strain MGAS27213_L₆₀₁P producing wild-type variant PBP2X-1 (penicillin G MIC = 0.016 μg/mL).