Affiliation:
1. Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology and College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, Zhejiang,...
2. Ningbo College of Health Sciences, Ningbo, Zhejiang, China
Abstract
ABSTRACT
Listeria monocytogenes
, a prominent foodborne pathogen responsible for zoonotic infections, owes a significant portion of its virulence to the presence of the phospholipase PlcB. In this study, we performed an in-depth examination of the intricate relationship between
L. monocytogenes
PlcB and host cell mitochondria, unveiling a novel participant in bacterial survival: the mitochondrial carboxylase propionyl-coenzyme A carboxylase (PCCA). Our investigation uncovered previously unexplored levels of interaction and colocalization between PCCA and PlcB within host cells, with particular emphasis on the amino acids 504–508 of PCCA, which play a pivotal role in this partnership. To assess the effect of PCCA expression on
L. monocytogenes
proliferation, PCCA expression levels were manipulated by siRNA-si-PCCA or pCMV-N-HA-PCCA plasmid transfection. Our findings demonstrated a clear inverse correlation between PCCA expression levels and the proliferation of
L. monocytogenes
. Furthermore, the effect of
L. monocytogenes
infection on PCCA expression was investigated by assessing PCCA mRNA and protein expression in HeLa cells infected with
L. monocytogenes
. These results indicate that
L. monocytogenes
infection did not significantly alter PCCA expression. These findings led us to propose that PCCA represents a novel participant in
L. monocytogenes
survival, and its abundance has a detrimental impact on bacterial proliferation. This suggests that
L. monocytogenes
may employ PlcB-PCCA interactions to maintain stable PCCA expression, representing a unique pro-survival strategy distinct from that of other intracellular bacterial pathogens.
IMPORTANCE
Mitochondria represent attractive targets for pathogenic bacteria seeking to modulate host cellular processes to promote their survival and replication. Our current study has uncovered mitochondrial carboxylase propionyl-coenzyme A carboxylase (PCCA) as a novel host cell protein that interacts with
L. monocytogenes
PlcB. The results demonstrate that PCCA plays a negative regulatory role in
L. monocytogenes
infection, as heightened PCCA levels are associated with reduced bacterial survival and persistence. However,
L. monocytogenes
may exploit the PlcB-PCCA interaction to maintain stable PCCA expression and establish a favorable intracellular milieu for bacterial infection. Our findings shed new light on the intricate interplay between bacterial pathogens and host cell mitochondria, while also highlighting the potential of mitochondrial metabolic enzymes as antimicrobial agents.
Funder
MOST | National Key Research and Development Program of China
MOST | National Natural Science Foundation of China
MOST | NSFC | NSFC-Zhejiang Joint Fund | 浙江省科学技术厅 | Natural Science Foundation of Zhejiang Province
Fundamental Research Funds for the Provincial Universities of Zhejiang
Ningbo Science and Technology Bureau
Publisher
American Society for Microbiology