. Author manuscript; available in PMC: 2022 Nov 22.

Published in final edited form as: Nat Rev Microbiol. 2022 Apr 1;20(9):529–541. doi: 10.1038/s41579-022-00721-0

Table 1.

Genetic, transcriptional, translational and post-translational modifications involved in bacterial heterogeneity

Type of variation	Cause	Outcome	Reference
Genetic variation	INDEL and SNPs in mps1-mps2-gap, mmpl4b	Switch of colony morphology from smooth to rough form, leading to more severe, persistent infections	⁵²
	SNPs in prpR	Multidrug tolerance to INH, RIF, OFX under propionate-rich condition	¹²
	Gene mutations in Rv0565c	Tolerance to ETH and PTH	¹³
	Frameshift mutations in glpk	Slower growth, reduced sensitivity to drug regimens containing PZA	^53,54
Transcriptional level	Induced expression of rpoB promoter II in response to RIF	Tolerance to RIF	⁵⁷
Transcriptional level	Various expression levels of KatG	Better survival following treatment with INH	⁵⁶
Translational level	Substitution of amino acids in RNA polymerase	Phenotypic resistance to RIF	⁵⁸
Translational level	Substitution of amino acid (S315T) in KatG	Resistance to INH	^59-62
Post-translational level	Lysine acetylation and methylation of HupB	Phenotypic resistance to INH	^63-65
	Phosphorylation at Y102 in MtrA	Tolerance to INH and VAN	⁶⁶
	Phosphorylation at T34 in PonA1	Increased MIC of RIF	³⁹

ETH, ethambutol; INDEL, insertion or deletion;INH, isoniazid;MIC, minimum inhibitory concentration; OFX, ofloxacin; PTH, prothionamide; PZA, pyrazinamide; RIF, rifampicin; SNP, single nucleotide polymorphism; VAN, vancomycin.