pbp2229-mediated nisin resistance mechanism in Listeria monocytogenes confers cross-protection to class IIa bacteriocins and affects virulence gene expression.
It was previously shown that enhanced nisin resistance in some mutants was associated with increased expression of three genes, pbp2229, hpk1021, and lmo2487, encoding a penicillin-binding protein, a histidine kinase, and a protein of unknown function, respectively. In the present work, we determined the direct role of the three genes in nisin resistance. Interruption of pbp2229 and hpk1021 eliminated the nisin resistance phenotype. Interruption of hpk1021 additionally abolished the increase in pbp2229 expression. The results indicate that this nisin resistance mechanism is caused directly by the increase in pbp2229 expression, which in turn is brought about by the increase in hpk1021 expression. We also found a degree of cross-protection between nisin and class IIa bacteriocins and investigated possible mechanisms. The expression of virulence genes in one nisin-resistant mutant and two class IIa bacteriocin-resistant mutants of the same wild-type strain was analyzed, and each mutant consistently showed either an increase or a decrease in the expression of virulence genes (prfA-regulated as well as prfA-independent genes). Although the changes mostly were moderate, the consistency indicates that a mutant-specific change in virulence may occur concomitantly with bacteriocin resistance development.
Department of Dairy and Food Science, Centre for Advanced Food Studies, LMC, The Royal Veterinary and Agricultural University, DK-1958 Frederiksberg C, Denmark. alg@kvl.dk
Anne
A
Gravesen
Birgitte
B
Kallipolitis
Kim
K
Holmstrøm
Poul Erik
PE
Høiby
Manilduth
M
Ramnath
Susanne
S
Knøchel
D001430:Bacteriocins / Q000145:classification / Q000494:pharmacology; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015870:Gene Expression; D005798:Genes, Bacterial; D008089:Listeria monocytogenes / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity; D016254:Mutagenesis, Insertional; D009154:Mutation; D009561:Nisin / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D014774:Virulence / Q000235:genetics
D001430:Bacteriocins; D004269:DNA, Bacterial; D009561:Nisin