TABLE 2.

Genes of lactobacilli putatively involved in stress resistance studied by mutant analysis

Functional category	Gene or locus tag(s)a	Identification approachb	Putative function	Organism	Mutant phenotype	Reference(s)
Cell envelope	lr1516	Microarray expression analysis	Putative esterase involved in PG biosynthesis and reorganization	L. reuteri ATCC 55730	Increased sensitivity to acid and bile	266, 277
	LBA1272	Dedicated approach	Cyclopropane fatty acid synthase	L. acidophilus NCFM	Increased sensitivity to acid	127
	dltD	Dedicated approach	d-Alanylation of LTA	L. rhamnosus GG	Increased sensitivity to simulated gastric juice (pH 2), increased sensitivity to defensins	188
	dltA	Dedicated approach	d-Alanylation of LTA	L. reuteri 100-23	Decreased adaptation to acid, increased sensitivity to defensins	270
	slpA	Dedicated approach	S-layer protein	L. acidophilus NCFM	Increased resistance to bile, decreased resistance to osmotic stress	127
	cdpA	Comp. gen. (weak similarity to S-layer proteins)	Cell division and separation protein	L. acidophilus NCFM	Increased resistance to bile, decreased resistance to osmotic stress	3, 127
Protection and repair DNA and proteins	dps	Microarray expression analysis	DNA protection during starvation and other stresses	L. reuteri ATCC 55730	No significantly increased sensitivity to bile	277
	clpL	Microarray expression analysis	Clp ATPase (chaperone)	L. reuteri ATCC 55730	Increased sensitivity to acid and bile	6, 277
	clpE	Microarray expression analysis	Clp ATPase (chaperone)	L. reuteri ATCC 55730	No significantly increased sensitivity to bile	277
	clpC	R-IVET	Clp ATPase (chaperone)	L. plantarum WCFS1	Reduced persistence capacity in vivo	31, 33
	msrB	IVET	Methionine sulfoxide reductase	L. reuteri 100-23	Reduced persistence capacity in vivo	268, 269
	luxS	Dedicated approach	Activated methyl cycle	L. rhamnosus GG	Reduced persistence capacity in vivo	135
2CRS regulators	LBA1524	Comp.gen. (in silico)	Histidine protein kinase	L. acidophilus NCFM	Increased sensitivity to acid	11
	LBA1430*	Microarray expression analysis	Histidine protein kinase	L. acidophilus NCFM	Increased sensitivity to bile	191
	LBA1431*	Microarray expression analysis	Response regulator	L. acidophilus NCFM	Increased sensitivity to bile	191
	LBA1432*	Microarray expression analysis	Hypothetical protein with similarity to RelA/SpoT	L. acidophilus NCFM	Increased sensitivity to bile	191
	rrp-1	Dedicated approach	Response regulator	L. sakei 23K	Increased sensitivity to acid	173
	rrp-48	Dedicated approach	Response regulator	L. sakei 23K	Increased sensitivity to acid	173
Active removal of stressors	copA	R-IVET	Copper-transporting ATPase	L. plantarum WCFS1	Reduced competitive ability in mouse intestine	31, 33
	gadC (LBA0057)	Comp.gen. (genome)c	Glutamate/γ-aminobutyrate antiporter	L. acidophilus NCFM	Increased sensitivity to acid	10
	LBA0867	Comp.gen. (genome)c	Transcriptional regulator	L. acidophilus NCFM	Increased sensitivity to acid and bile	10
	LBA0995	Comp.gen. (genome)c	Amino acid permease	L. acidophilus NCFM	Increased sensitivity to acid and bile	10
	LBA0996	Comp.gen. (genome)c	Ornithine decarboxylase	L. acidophilus NCFM	Increased sensitivity to acid but increased resistance to bile	10
	Lr1265	Microarray expression analysis	Multidrug resistance protein (ABC transporter family)	L. reuteri ATCC 55730	Decreased adaptation to bile	277
	Lr1584	Microarray expression analysis	MDR protein (major facilitator family)	L. reuteri ATCC 55730	Decreased adaptation to bile	277
	LBA1427*	Microarray expression analysis	Putative oxidoreductase, role in bile salt modification?	L. acidophilus NCFM	Increased tolerance to bile	191
	LBA1428*	Microarray expression analysis	Hypothetical protein with similarity to redox proteins, role in bile salt modification?	L. acidophilus NCFM	Increased tolerance to bile	191
	LBA1429*	Microarray expression analysis	MDR protein (major facilitator family)	L. acidophilus NCFM	Increased sensitivity to bile	191
	bshA	Comp.gen. (genome)	Bile salt hydrolase	L. acidophilus NCFM	Inability to hydrolyze bile salts conjugated to chenodeoxycholic acid; no altered bile tolerance	165
	bshB	Comp.gen. (genome)	Bile salt hydrolase	L. acidophilus NCFM	Inability to hydrolyze bile salts conjugated to taurine; no altered bile tolerance	165
	LJ0056, LJ1147, LJ1413	Comp.gen. (genome)	Bile salt hydrolases	L. johnsonii NCC533	A triple mutant showed gut persistence similar to that of the wild type	67
	bsh1	Comp.gen. (genome)	Bile salt hydrolase	L. plantarum WCFS1	Reduced tolerance to glycodeoxycholic acid but not to taurodeoxycholic acid	132

^a*, these genes are located in an operon in L. acidophilus NCFM (191).

^bComp.gen., comparative genomics.

^cGenome, information based on genome sequence.