TABLE 2.

Main mechanisms of antibiotic resistance in pyogenic streptococci.

Mechanism	Target antibiotics	Examples	Location	References
Enzyme inactivation	β-lactam	β-lactamases via hydrolisis, e.g., BL2b; TEM-1; TEM-47; TEM-71; TEM-89; TEM-95	Chromosome	Vélez et al., 2017
	Aminoglycosides	Aminoglycoside-modifying enzymes (AMEs) – APH(3′)-IIIa; ANT(6)-Ia; AAC(6′)-APH(2′′)	Chromosome and MGE, e.g., Tn4001, Tn5405 and Tn3706 (Tn4001 derivative)	Galimand et al., 1999; Prudhomme et al., 2002; Kristich et al., 2014; Cattoir, 2016; Doumith et al., 2017
	Chloramphenicol	Chloramphenicol O-acetyltransferase (CAT) enzyme encoded by genetic determinants cat(pC194); cat(pC221); cat(pSCS7); catS, and catQ	Plasmid and conjugative transposon Tn1545 and Tn5253-like	Schwarz et al., 2004; Woodford, 2005; Del Grosso et al., 2011; Mingoia et al., 2015
	Lincosamide	LinB/A catalyze adenylylation of antibiotics	MGE	Haenni et al., 2010; Rato et al., 2013; Osei Sekyere and Mensah, 2019
Preventing drug access to target	Tetracycline	Efflux pumps Tet(K)	Chromosomal insertion element	Rato et al., 2013; Emaneini et al., 2014; Nguyen et al., 2014
	Quinolones	Efflux pumps PmrA	Chromosome	Martinez-Garriga et al., 2007
	Macrolides	Efflux pumps Mef and Msr	MGE such as Tn917 and bacteriophage Φ m46.1.	Brenciani et al., 2004, 2007; Di Luca et al., 2010; Del Grosso et al., 2011; Rato et al., 2013; Hadjirin et al., 2014
	Tetracycline	Tet(M), Tet(O), Tet(Q), Tet(S), Tet(T), Tet(W) ribosomal protection proteins dissociate tetracycline from ribosome	MGE (Tn916 and Tn3701) and bacteriophages Φ m46.1	Brenciani et al., 2004, 2007; Liu et al., 2008; Nikaido, 2009; Di Luca et al., 2010; Nguyen et al., 2014; Da Cunha et al., 2014; Silva et al., 2015; Kim et al., 2018
Target modification	Quinolones and Fluoroquinolones	Point mutations primarily in quinolone resistance-determining regions (QRDRs), of parC and gyrA genes	Chromosome. Evidence for horizontal transfer of QRDR between streptococci has been reported.	Ferrándiz et al., 2000; Balsalobre et al., 2003; Orscheln et al., 2005; Pletz et al., 2006; Duesberg et al., 2008; Hooper and Jacoby, 2016; Pham et al., 2019
	Tetracycline; Aminoglycosides	Modification in rRNA	Chromosomal mutation	Nguyen et al., 2014; Lupien et al., 2015
	Macrolides	Modification of 23S rRNA and/or ribosomal proteins L4 and L22 determinants	Chromosomal mutation	Malbruny et al., 2002; Jalava et al., 2004
	β-lactam	Modification of penicillin-binding proteins 1A [PBP1A], PBP2B, and PBP2X	Chromosomal mutation	Kimura et al., 2008, 2013; Pillai et al., 2009; Fuursted et al., 2016; Moroi et al., 2019; Vannice et al., 2019; Musser et al., 2020
	Macrolides-Lincosamide- Streptogramin B	Modification by methylation of rRNA (erm-class genes)	The erm(B) and erm(TR) genes are found in the chromosome of streptococci and conjugative transposons, such as Tn916 family and Tn5397 elements	Brenciani et al., 2007, 2011; Cattoir, 2016