Intrahost passage alters SigB-dependent acid resistance and host cell-associated kinetics of Listeria monocytogenes

Abstract

Listeria monocytogenes is a foodborne pathogen that causes gastroenteritis, maternofetal infections and meningoencephalitis in humans. Here we report that an intrahost genome mutation alters bacterial acid resistance and the abilities for replication/invasion in tissue cell culture. Among the L. monocytogenes isolates from the recent outbreak in Japan, we found that one food strain, 668, exhibited the greatest acid resistance, whereas one human clinical strain, 690, sharing identical pulsed-field gel electrophoresis (PFGE) and ribotyping patterns, exhibited an acid-sensitive phenotype. Passage of the 668 food strain through the mouse intestine increased its acid sensitivity without altering the macrogenotypes, indicating intrahost alteration of the bacterial acid-resistant phenotype. Genetic and proteomic analyses revealed a link between acid resistance and SigB (RNA polymerase SigmaB subunit) activity. Compared with the strain 668, the clinical and 4 of 5 mice-passaged strains showed a mutation in the rsbW locus, whose product controls the regulation of SigB activity. Corresponding to the SigB activity, the host-passaged strains had reduced abilities to survive inside macrophages and to invade Caco-2 cells, compared with the food strain 668. Overall, we have demonstrated the first example of a host environment promoting the alteration of SigB-dependent acid resistance and host cell-associated actions of L. monocytogenes. Our study provides new insight into the potential role of intrahost environment in the process of bacterial evolution.