TABLE 2.

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

Functional categoryGene or locus tag(s)aIdentification approachbPutative functionOrganismMutant phenotypeReference(s)
Cell envelopelr1516Microarray expression analysisPutative esterase involved in PG biosynthesis and reorganizationL. reuteri ATCC 55730Increased sensitivity to acid and bile266, 277
LBA1272Dedicated approachCyclopropane fatty acid synthaseL. acidophilus NCFMIncreased sensitivity to acid127
dltDDedicated approachd-Alanylation of LTAL. rhamnosus GGIncreased sensitivity to simulated gastric juice (pH 2), increased sensitivity to defensins188
dltADedicated approachd-Alanylation of LTAL. reuteri 100-23Decreased adaptation to acid, increased sensitivity to defensins270
slpADedicated approachS-layer proteinL. acidophilus NCFMIncreased resistance to bile, decreased resistance to osmotic stress127
cdpAComp. gen. (weak similarity to S-layer proteins)Cell division and separation proteinL. acidophilus NCFMIncreased resistance to bile, decreased resistance to osmotic stress3, 127
Protection and repair DNA and proteinsdpsMicroarray expression analysisDNA protection during starvation and other stressesL. reuteri ATCC 55730No significantly increased sensitivity to bile277
clpLMicroarray expression analysisClp ATPase (chaperone)L. reuteri ATCC 55730Increased sensitivity to acid and bile6, 277
clpEMicroarray expression analysisClp ATPase (chaperone)L. reuteri ATCC 55730No significantly increased sensitivity to bile277
clpCR-IVETClp ATPase (chaperone)L. plantarum WCFS1Reduced persistence capacity in vivo31, 33
msrBIVETMethionine sulfoxide reductaseL. reuteri 100-23Reduced persistence capacity in vivo268, 269
luxSDedicated approachActivated methyl cycleL. rhamnosus GGReduced persistence capacity in vivo135
2CRS regulatorsLBA1524Comp.gen. (in silico)Histidine protein kinaseL. acidophilus NCFMIncreased sensitivity to acid11
LBA1430*Microarray expression analysisHistidine protein kinaseL. acidophilus NCFMIncreased sensitivity to bile191
LBA1431*Microarray expression analysisResponse regulatorL. acidophilus NCFMIncreased sensitivity to bile191
LBA1432*Microarray expression analysisHypothetical protein with similarity to RelA/SpoTL. acidophilus NCFMIncreased sensitivity to bile191
rrp-1Dedicated approachResponse regulatorL. sakei 23KIncreased sensitivity to acid173
rrp-48Dedicated approachResponse regulatorL. sakei 23KIncreased sensitivity to acid173
Active removal of stressorscopAR-IVETCopper-transporting ATPaseL. plantarum WCFS1Reduced competitive ability in mouse intestine31, 33
gadC (LBA0057)Comp.gen. (genome)cGlutamate/γ-aminobutyrate antiporterL. acidophilus NCFMIncreased sensitivity to acid10
LBA0867Comp.gen. (genome)cTranscriptional regulatorL. acidophilus NCFMIncreased sensitivity to acid and bile10
LBA0995Comp.gen. (genome)cAmino acid permeaseL. acidophilus NCFMIncreased sensitivity to acid and bile10
LBA0996Comp.gen. (genome)cOrnithine decarboxylaseL. acidophilus NCFMIncreased sensitivity to acid but increased resistance to bile10
Lr1265Microarray expression analysisMultidrug resistance protein (ABC transporter family)L. reuteri ATCC 55730Decreased adaptation to bile277
Lr1584Microarray expression analysisMDR protein (major facilitator family)L. reuteri ATCC 55730Decreased adaptation to bile277
LBA1427*Microarray expression analysisPutative oxidoreductase, role in bile salt modification?L. acidophilus NCFMIncreased tolerance to bile191
LBA1428*Microarray expression analysisHypothetical protein with similarity to redox proteins, role in bile salt modification?L. acidophilus NCFMIncreased tolerance to bile191
LBA1429*Microarray expression analysisMDR protein (major facilitator family)L. acidophilus NCFMIncreased sensitivity to bile191
bshAComp.gen. (genome)Bile salt hydrolaseL. acidophilus NCFMInability to hydrolyze bile salts conjugated to chenodeoxycholic acid; no altered bile tolerance165
bshBComp.gen. (genome)Bile salt hydrolaseL. acidophilus NCFMInability to hydrolyze bile salts conjugated to taurine; no altered bile tolerance165
LJ0056, LJ1147, LJ1413Comp.gen. (genome)Bile salt hydrolasesL. johnsonii NCC533A triple mutant showed gut persistence similar to that of the wild type67
bsh1Comp.gen. (genome)Bile salt hydrolaseL. plantarum WCFS1Reduced tolerance to glycodeoxycholic acid but not to taurodeoxycholic acid132
  • a *, these genes are located in an operon in L. acidophilus NCFM (191).

  • b Comp.gen., comparative genomics.

  • c Genome, information based on genome sequence.